Wiley Acta Medica Okayama 2090-0007 2026 2026 Association Between Early Posttransplant Graft Perfusion and CLAD‐Free Survival After Single Lung Transplantation 7647492 EN Shin Tanaka Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Ishihara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Yujiro Kubo Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Haruchika Yamamoto Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumi Nakajima Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuji Okahara Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background The physiological relevance of postoperative perfusion distribution after single lung transplantation (SLT) remains poorly defined, as asymmetric blood flow toward the graft is often regarded as an inherent consequence of the remaining native lung. This study aimed to determine whether the graft-directed perfusion ratio assessed by quantitative lung perfusion scintigraphy (QLPS) in the early postoperative period serves as an early physiological marker after SLT. Methods We retrospectively analyzed SLT recipients who underwent surgery at Okayama University Hospital between 1998 and 2021 and completed QLPS approximately 3 months posttransplant. The graft perfusion ratio (graft flow/total pulmonary flow × 100%) was quantified, and recipients were classified into high (≥ 80%) and low (< 80%) perfusion groups. CLAD-free survival, overall survival, and longitudinal perfusion changes were compared using Kaplan–Meier analysis and repeated-measures ANOVA. Results Recipients with higher graft perfusion demonstrated significantly better CLAD-free survival (p = 0.027). Overall survival was higher in the high-perfusion group, although the difference did not reach statistical significance (p = 0.075). Repeated-measures ANOVA revealed a significant group-by-time interaction (p = 0.019): recipients who developed CLAD had lower graft perfusion as early as 3 months after transplantation, followed by a progressive decline, whereas those who did not develop CLAD maintained stable perfusion. In the multivariable Cox analysis, higher graft perfusion was associated with a lower hazard of reaching the composite CLAD-free survival endpoint. Conclusions Early postoperative graft perfusion assessed by QLPS may serve as a noninvasive physiological marker after SLT. Higher graft-directed perfusion was associated with a lower hazard of reaching the composite CLAD-free survival endpoint and may aid early risk stratification and posttransplant surveillance. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Radiogenomic Analysis of Contrast-Enhanced MRI for Predicting Pathogenic BRCA Variants in Ovarian Cancer 317 325 EN Hayato Saito Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Ryohei Fukui Department of Radiological Technology, Faculty of Health Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Akihiro Tada Okayama Diagnostic Imaging Center Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/71341 This study evaluated the feasibility of predicting pathogenic BRCA1/2 variants in ovarian cancer using radiogenomic analysis of contrast-enhanced MRI. Twenty six patients were analyzed, including 14 with pathogenic BRCA1/2 variants and 12 without. Contrast enhanced MRI was used to generate two dimensional (2D) and three dimensional (3D) tumor segmentations. Radiomic features extracted with PyRadiomics were reduced using least absolute shrinkage and selection operator (LASSO) regression, yielding two selected features. Linear discriminant analysis (LDA) models were trained on 18 patients and tested on 8, with performance assessed using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve. The DeLong test compared AUCs between segmentation methods. Automated machine learning (AutoML) was performed with a training set of 20 patients and a test set of 6, with multiple performance metrics calculated. LDA achieved approximately 60% accuracy in both 2D and 3D test datasets. AUCs were 0.80 (3D) and 0.77 (2D), with no significant difference (p=0.85). AutoML identified CatBoost_BAG_L2_FULL as the optimal model, achieving accuracy above 80%. MRI-based radiogenomic analysis demonstrated moderate classification performance for identifying pathogenic BRCA1/2 variants in ovarian cancer. These preliminary findings suggest a potential role for noninvasive prediction, warranting further validation in larger cohorts. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Prognostic Value of Combined Preoperative CALLY and SII Assessment in Patients Undergoing Resection for Esophageal Squamous Cell Carcinoma 299 308 EN Tao Xu Department of Oncology, The General Hospital of Western Theater Command Ying Zheng Department of Oncology, The General Hospital of Western Theater Command Xuemei Huang Department of Oncology, The General Hospital of Western Theater Command Hong Luo Department of Oncology, The General Hospital of Western Theater Command Original Article /10.18926/AMO/71339 This study evaluated the prognostic significance of the C-reactive protein–albumin–lymphocyte (CALLY) index and systemic immune-inflammation (SII) index in predicting postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was performed on clinical data from 102 patients with ESCC who underwent surgical resection at Western Theater General Hospital of China between January 2020 and July 2023. The associations between preoperative CALLY and SII indices and relapse-free survival (RFS) and overall survival (OS) were examined. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified using Cox proportional hazards regression analysis. Patients with a high CALLY index had significantly longer RFS (HR=0.30, 95% CI: 0.13-0.71), and those with a low SII index also had significantly longer RFS (HR=2.23, 95% CI: 1.12-4.41). Similarly, patients with a high CALLY index had significantly longer OS (HR=0.27, 95% CI: 0.13-0.55), and those with a low SII index had significantly longer OS (HR=2.27, 95% CI: 1.09-4.71). When patients were stratified into four groups, the low-CALLY–high-SII group showed significantly shorter RFS than the high-CALLY–low-SII group (HR=0.26, 95% CI: 0.11-0.61; p=0.013), and OS was also significantly worse in the low-CALLY–high-SII group (HR=0.22, 95% CI: 0.09-0.54; p=0.016). Univariate Cox regression analysis identified both CALLY and SII as significant prognostic factors. In multivariate analysis, the CALLY index and N stage were independently associated with RFS, whereas only tumor size remained independently associated with OS. The combined assessment of preoperative CALLY and SII indices may be useful for prognostic stratification in patients with ESCC undergoing upfront surgical resection. It may help identify high-risk patient subgroups with distinct survival outcomes, thereby providing a potential rationale for stratifying postoperative surveillance and tailoring individualized adjuvant strategies, although validation in larger prospective cohorts is warranted. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0300-2896 61 5 2025 Histological Features and Gene Expression Profiling in Lung Transplantation From Donation After Circulatory Death 299 302 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohisa Sakaue Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yujiro Kubo Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Tatsuya Hayashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Elvira Ramil Sequencing and Molecular Biology Unit, Hospital Universitario Puerta de Hierro-Majadahonda Antonio J. Sánchez-López Biobank, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana María Jose Coronado Confocal Microscopy Unit, Hospital Universitario Puerta de Hierro-Majadahonda Lucas Hoyos Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Alejandra Romero Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences David Gomez-de-Antonio Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 2026 SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer e77909 EN Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kun Zhao Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Advanced International and Information Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2－/－ mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2－/－ T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2－/－ CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2－/－ CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell–based cancer immunotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0929-1903 32 5 2025 Tob negatively regulates NF-κB activation in breast cancer through its association with the TNF receptor complex 573 583 EN Miho Tokumasu Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuko Sato Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Taku Ito-Kureha Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Mizuki Yamamoto Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo Nao Ohmine Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Kentaro Semba Department of Life Science and Medical Bioscience, Waseda University Jun-ichiro Inoue The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) Tadashi Yamamoto Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University NF-κB mediates transcriptional regulation crucial to many biological functions, and elevated NF-κB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-κB signaling would facilitate the development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-κB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-κB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-κB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-κB upon TNF-α treatment, whereas overexpression of Tob inhibited TNF-α stimulation-dependent NF-κB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-κB. No potential conflict of interest relevant to this article was reported.

XMLink Acta Medica Okayama 2005-0380 37 2026 Nationwide survey of hereditary breast and ovarian cancer–related clinical practice in gynecologic oncology in Japan: a joint study by the Japan Society of Gynecologic Oncology (JSGO) and the Japan Society of Obstetrics and Gynecology (JSOG) e122 EN Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Hidemichi Watari Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine and Faculty of Medicine Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinya Sato Department of Obstetrics and Gynecology, Tottori University School of Medicine Kenichi Harano Department of Medical Oncology, National Cancer Center Hospital East Satoru Nagase Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Masaki Mandai Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University Yuko Sasajima Department of Pathology, Teikyo University Hospital Tamotsu Sudo Department of Cancer Genetics & Genomics, Fujita Health University, School of Medicine Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Yusuke Kobayashi Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba Kei Kawana Department of Obstetrics and Gynecology, Nihon University School of Medicine Mikio Mikami Department of Medical Science, Shonan University of Medical Science Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Daisuke Aoki International University of Health and Welfare Graduate School Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine Objective: To evaluate the current status of hereditary breast and ovarian cancer (HBOC)–related clinical practice in Japan, including genetic testing, risk-reducing surgery, and surveillance systems, and to identify institutional gaps and unmet needs. Methods: A nationwide questionnaire survey was conducted between February and April 2024 targeting 647 Japan Society of Obstetrics and Gynecology–affiliated training facilities and gynecologic oncology centers. Institutional-level data on genetic testing, homologous recombination deficiency (HRD) testing, risk-reducing salpingo-oophorectomy (RRSO), postoperative management, surveillance practices, and healthcare infrastructure were collected. Responses from 248 institutions (response rate, 38.3%) were analyzed descriptively. Results: BRCA1/2 genetic testing was performed in 83% of institutions, and HRD testing using the myChoice® CDx system in 87%. However, only 30% offered universal BRCA1/2 testing for ovarian, fallopian tube, or peritoneal cancer, and testing indications varied widely. Genetic counseling resources were uneven, with 29% lacking on-site genetic specialists, driven mainly by institutional characteristics rather than geographic location. RRSO was performed in 50% of institutions, predominantly laparoscopically. While management of occult carcinoma after RRSO was largely consistent, postoperative management of serous tubal intraepithelial carcinoma (STIC) and positive peritoneal cytology varied substantially. Over 70% of institutions reported a need for expanded insurance coverage for genetic services and preventive care. Conclusion: Although HBOC-related genetic testing and preventive strategies are widely implemented in Japan, this nationwide survey revealed critical structural and evidence gaps, particularly in institutional capacity and the management of evidence-limited scenarios such as STIC, underscoring the need for system-level improvement. No potential conflict of interest relevant to this article was reported.

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Report cr.26-0502 EN Yuya Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Naomi Asano Division of Transfusion and Cell Therapy, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery, Okayama University Hospital Shuji Okahara Department of General Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, Japan Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital INTRODUCTION: Cold agglutinins (CAs) are immunoglobulin M autoantibodies that induce red blood cell agglutination at low temperatures and may cause hemolytic or thrombotic complications during procedures associated with hypothermia. In lung transplantation (LT), blood may be exposed to low temperatures within the reperfused lung graft and the extracorporeal circulation circuit, potentially increasing the risk of CA-mediated complications. However, the perioperative significance of CAs in this setting remains unclear, and optimal management has not been established. We report a case of successful bilateral LT in a patient with high-thermal-amplitude CAs managed with preoperative plasma exchange (PLEX) and strict intraoperative temperature control. CASE PRESENTATION: A 55-year-old man with diffuse panbronchiolitis and secondary pulmonary hypertension was listed for bilateral LT. Preoperative testing incidentally revealed clinically significant CAs, with a titer of 1:128 at 4°C and a thermal amplitude of 30°C. Because intraoperative blood temperature might approach this threshold despite active warming, a single preoperative session of PLEX using 36 units of fresh frozen plasma was performed to reduce the risk of a CA-mediated complication. Bilateral LT was subsequently completed under meticulous temperature management, including extracorporeal circulation maintained at 37.5°C, continuous systematic warming, avoidance of topical ice application, and rewarming of the donor lungs before reperfusion. After surgery, the CA titer decreased to 1:32. The postoperative course was uneventful, without thromboembolic events, primary graft dysfunction, or bronchial complications. CONCLUSIONS: LT may be performed safely in selected patients with high-thermal-amplitude CAs when careful perioperative temperature control is combined with preoperative PLEX. PLEX should be considered when the anticipated intraoperative temperature is expected to approach the patient’s thermal amplitude threshold. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 5 2026 Breast ultrasound screening in young adult women undergoing infertility treatment at an infertility clinic: a retrospective observational study 1093 1101 EN Kanako Nakano Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Marie Saji Department of Breast and Endocrine Surgery, Okayama University Hospital Rei Hirata Department of Senior Embryologist, Okayama Couple’s Clinic Motomi Yukawa Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center Shizuka Okuda Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center Miyu Hirano Department of Medical Technology, Okayama Couple’s Clinic Toshihiro Habara Department of Reproductive Medicine, Okayama Couple’s Clinic Nobuyoshi Hayashi Department of Reproductive Medicine, Okayama Couple’s Clinic Background Young adult women are increasingly undergoing infertility treatment; however, evidence regarding breast cancer screening in this population remains limited. Given that most women in this age group have dense breast tissue, for which mammography has limited sensitivity, breast ultrasound (US) is often used as a screening modality. A diagnosis of breast cancer during infertility treatment may affect both oncologic management and reproductive planning. This study aimed to examine the clinical relevance of breast US in women in their 30s undergoing infertility treatment at an infertility clinic. Methods We retrospectively analyzed 1,336 women aged 30–39 years who underwent screening breast US between November 1, 2018, and June 30, 2025. Analyses were performed on a per-woman basis, including only the first screening examination for each participant. Breast composition was categorized according to the BI-RADS 5th edition Atlas. Screening outcomes―including recall rate, positive predictive value (PPV), cancer detection rate, and US findings (mass and non-mass findings)―were assessed using medical records. The continuation of infertility treatment, defined as ongoing or resumed treatment during the diagnostic evaluation period, was descriptively evaluated as part of the clinical context. Results Of the 1,336 women, 1,277 (95.6%) were classified as having dense breasts. A total of 140 (10.5%) women were recalled for further evaluation. In these recalled cases, 147 findings were identified, comprising 113 mass lesions (76.8%) and 34 non-mass findings (23.1%). Four breast cancers were identified, corresponding to a cancer detection rate of 0.30% and a PPV of 2.86%. Histological diagnoses included one mucinous carcinoma, two invasive carcinomas of no special type (NST), and one ductal carcinoma in situ (DCIS). Following diagnostic evaluation, 124 recalled women (88.6%) continued infertility treatment. Conclusions Breast US screening in women in their 30s undergoing infertility treatment provides descriptive findings within a specific clinical setting. The observed cancer detection rate appears to be within the range reported in previous studies; however, direct comparisons are limited due to differences in study populations and clinical contexts. The clinical course following recall was described as part of the screening pathway. Further prospective and multicenter studies are required to clarify the clinical significance of breast US screening in this population. No potential conflict of interest relevant to this article was reported.

AME Publishing Company Acta Medica Okayama 2304-3865 15 2 2026 First-line fulvestrant vs. anastrozole in hormone receptor-positive advanced breast cancer: insights from the final FALCON trial results 22 EN Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maki Tanioka Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0934-9723 2026 Streptococcal toxic shock syndrome caused by ST525 Streptococcus dysgalactiae subsp. equisimilis with genomic characterization of virulence and antimicrobial resistance EN Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Maki Tanioka Clinical Oncology Center, Okayama University Hospital Hideharu Hagiya Research Center for Intestinal Health Science, Okayama University Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of severe invasive infections. We describe the clinical course of an immunocompromised patient with advanced breast cancer who developed streptococcal toxic shock syndrome, necrotizing fasciitis, and disseminated intramuscular abscesses caused by a multidrug-resistant Lancefield group G SDSE isolate, alongside a comprehensive genomic characterization of its virulence and antimicrobial resistance profiles. Genomic analysis identified the isolate as emm subtype stG840.0 and sequence type 525 (ST525), harboring genes encoding several virulence-associated factors, including an emm-like gene encoding an M-like surface protein, streptokinase, streptolysin O, streptolysin S, and SpeG. Through comprehensive genomic analysis of the highly virulent SDSE isolate, we provided insights into its underlying genetic background. Further accumulation of genomic data is expected to fully elucidate the mechanisms of virulence and antimicrobial resistance in SDSE. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2699-9307 6 6 2026 NUAK2 Inhibition Enhances Macromolecular Drug Delivery in a 3D Fibrotic Model of the Pancreatic Tumor Microenvironment e202500237 EN Misaki Nakamura Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Mayu Ohira Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Haruko Ohta‐Okano Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Reika Nakamura Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yu Seno Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Saaya Yara Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Sakura Fujita Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Daichi Shibata Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masaya Yamamoto Department of Materials Processing Graduate School of Engineering, Tohoku University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Osada Department of Molecular Imaging and Theranostics Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) Horacio Cabral Department of Bioengineering Graduate School of Engineering, The University of Tokyo Atsushi Masamune Division of Gastroenterology Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Pancreatic ductal adenocarcinoma (PDAC) features a fibrotic tumor microenvironment that impedes drug delivery and significantly limits the successful clinical application of nanomedicines. Targeting signaling in pancreatic stellate cells (PSCs), which drive fibrosis via excessive secretion of extracellular matrix proteins such as collagen I, may be useful in overcoming this fibrotic barrier. The AMPK-related kinases NUAK1/2 have recently gained interest as promoters of fibrosis, but whether they play a profibrotic role in PSCs remains unknown. Here, patient PSCs are used to assess NUAK1/2 involvement in the PDAC fibrotic barrier. Leveraging a 3D cell culture model of PDAC fibrosis, the effect of targeting NUAK1/2 on the permeability of macromolecular dextrans of various sizes, as well as physiologically relevant macromolecules, albumin and IgG, and clinical nanomedicines, Doxil and Abraxane, is investigated. NUAK1/2 inhibition is shown to diminish collagen I to enhance macromolecular permeability, via a mechanism independent of established pathways involving transforming growth factor-β (TGFβ) and yes-associated protein (YAP). Through isoform-specific knockdown, predominant NUAK2 involvement is demonstrated. Mechanistically, actin stress fiber regulation by NUAK2 is shown to be important. Altogether, these results show in vitro that NUAK2 promotes fibrotic signaling in PSCs and may be targeted to enhance macromolecular drug delivery in PDAC. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 43 11 2025 Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2–Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial 1302 1313 EN Toshinari Yamashita Department of Breast Surgery and Oncology, Kanagawa Cancer Center Shigehira Saji Department of Medical Oncology, Fukushima Medical University Toshimi Takano Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Michiko Tsuneizumi Department of Breast Surgery, Shizuoka General Hospital Akiyo Yoshimura Department of Breast Oncology, Aichi Cancer Center Hospital Masato Takahashi Department of Breast Surgery, Hokkaido University Hospital Junji Tsurutani Advanced Cancer Translational Research Institute, Showa University Tsuguo Iwatani Breast and Endocrine Surgery, Okayama University Hospital Masahiro Kitada Department of Breast Disease Center, Asahikawa Medical University Hospital Hiroshi Tada Department of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital Natsuko Mori Department of Breast Surgery, Seirei Hamamatsu General Hospital Toru Higuchi Department of Breast Unit, Japanese Red Cross Saitama Hospital Tsutomu Iwasa Department of Medical Oncology, Kindai University Hospital Kazuhiro Araki Department of Breast Medical Oncology, Gunma Prefectural Cancer Center Kei Koizumi Department of Surgery 1, Division of Breast Surgery, Hamamatsu University School of Medicine Hiroki Hasegawa Medical HQs, Eisai Co, Ltd Yohei Uchida Medical HQs, Eisai Co, Ltd Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University Norikazu Masuda Department of Breast Surgery, Graduate School of Medicine, Kyoto University Purpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC. Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33. Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin. Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC. No potential conflict of interest relevant to this article was reported.

AME Publishing Company Acta Medica Okayama 2304-3865 13 5 2024 Primary angiosarcoma of the breast: a literature review 68 EN Yidan Zhu Department of Breast Surgery, Liaoning Cancer Hospital & Institute Shogo Nakamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Yoko Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Xinfeng Zhang Department of Breast Surgery, Liaoning Cancer Hospital & Institute Maki Tanioka Department of Clinical AI Human Resources Development Program, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background and Objective: Primary angiosarcoma of the breast (PBA) is an extremely rare and heterogeneous disease. PBA is difficult to diagnose and has a poor prognosis. In order to better understand the disease and provide evidence-based treatment for PBA patients, a review of the published literature in the English language was conducted. Methods: A literature review in agreement with the PRISMA protocol was conducted. Medline and Cochrane databases were searched for English articles on PBA patients in September 2023 with a predetermined strategy. The articles were categorized and assessed based on hierarchical levels of scientific evidence. Key Content and Findings: A total of 255 articles were identified, among these 137 publications which included 1,888 patients met the criteria for inclusion in the final analysis. No prospective, randomized trials exclusive to PBA have been recognized. This article provides an overview of the most current and comprehensive evidence concerning the epidemiology, etiology, genomic features, clinical presentations, diagnosis, treatment, and prognosis of PBA. Conclusions: Despite the fact that current evidence is largely derived from retrospective studies, database analyses, and case reports, we utilized this information to tackle important clinical questions concerning optimal patient management practices for PBA. Complete surgical excision continues to be the mainstay treatment for PBA. However, the effectiveness of adjuvant therapies is still unclear. This narrative review highlights the urgent need for more rigorously designed research to enhance the management and treatment strategies for PBA. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 0022-2593 2026 Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages EN Arcangela De Nicolo Department of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori Diana M Eccles Faculty of Medicine, University of Southampton Kirsimari Aaltonen Duodecim Medical Publications Ltd Pia Alhopuro HUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of Helsinki Sarah Louise Ariansen Department of Medical Genetics, Oslo University Hospital Michela Biancolella Department of Biology, University of Rome Tor Vergata Sandrine M Caputo Department of Genetics, Institut Curie Olivier Caron Département de Médecine Oncologique, Gustave Roussy Pietro Cavalli Medical Genetics, IRCCS Humanitas Research Hospital Jianbang Chiang Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Kathleen B M Claes Center for Medical Genetics, Ghent University Hospital Edgar Christian S Cuaresma St. Luke’s Medical Center Miguel de la Hoya Hospital Clínico San Carlos, Molecular Oncology Laboratory, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos Antoine De Pauw Department of Genetics, Institut Curie Orland Díez Vall d’Hebron Hospital Universitari, Area of Clinical and Molecular Genetics, Vall d’Hebron Barcelona Hospital Campus Mev Domínguez-Valentin Institute of Cancer Research, Department of Tumor Biology, The Norwegian Radium Hospital Hans Ehrencrona Department of Clinical Genetics, Pathology and Molecular Diagnostics, Skåne University Hospital Magnhild K Fjeldvær Department of Medical Genetics, Oslo University Hospital Florentia Fostira INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos Marie Belle D Francia St. Luke’s Medical Center Javier Galego-Carro Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela Encarna B Gómez García Department of Clinical Genetics, Maastricht University Medical Centre Nur Tiara Hassan Cancer Research Malaysia Jan Hauke Faculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital Cologne Akira Hirasawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Clinical Genomic Medicine, Okayama University Xin Huang Department of Breast Surgery, Peking Union Medical College Hospital Elaine Marisse H Ilagan-Cargullo St. Luke’s Medical Center Issei Imoto Aichi Cancer Center Research Institute Sowmya Jonnagadla Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, Si Manasadevi Karthikeyan Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Petra Kleiblova Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Irene Konstantopoulou INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos Artur Kowalik Department of Molecular Diagnostics, Holy Cross Cancer Centre Anders Kvist Department of Clinical Sciences Lund, Division of Oncology, Lund University Fabienne Lesueur PSL Research University Shao-Tzu Li Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Adrià López-Fernández Hereditary Cancer Genetics Group, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO) Eva Machackova Center for Medical Genetics, Masaryk Memorial Cancer Institute Alexandra Martins Univ Rouen Normandie, Inserm U1245 Arjen R Mensenkamp Department of Human Genetics, Radboud University Medical Center Yukihide Momozawa Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences Gemma Montalban Department of Oncogenetics, MRC Holland Alvaro N A Monteiro Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute Heli Nevanlinna HUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of Helsinki Joanne Ngeow Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Edenir Inez Palmero Molecular Oncology Research Center, Barretos Cancer Hospital Inge Sokilde Pedersen Molecular Diagnostics and Clinical Cancer Research Centre, Aalborg University Hospital Frances Victoria F Que St. Luke’s Medical Center Marta Santamariña Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela Elizabeth Santana dos Santos Department of Medical Oncology, A.C. Camargo Cancer Center Christian F Singer Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of Vienna Monika Siołek Genetic Clinic, Holy Cross Cancer Centre Angela R Solano Departmento de Analisis Clinicos, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC) Jana Soukupova Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Priyadharshini d/o Suresh Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Magdalena Szczepaniak Department of Molecular Diagnostics, Holy Cross Cancer Centre Yen Y Tan Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of Vienna Soo Hwang Teo Cancer Research Malaysia Emma Tham Department of Clinical Genetics and Genomics, Karolinska University Hospital Mads Thomassen Department of Clinical Genetics, Odense University Hospital Georgios Tsaousis Genekor Medical S.A Thomas van Overeem Hansen Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet Ana Vega Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela Eladio A Velasco-Sampedro Instituto de Biología y Genética Molecular, Splicing and Genetic Susceptibility to Cancer, Consejo Superior de Investigaciones Científicas - Universidad de Valladolid (CSIC-UVa) Teresia Wangensteen Department of Medical Genetics, Oslo University Hospital Barbara Wappenschmidt Faculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital Cologne Drakoulis Yannoukakos INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos Sook-Yee Yoon Cancer Research Malaysia Amanda B Spurdle Population Health Program, QIMR Berghofer Medical Research Institute Paolo Radice Department of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers’ genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Association Between Initial Symptoms and Clinical Outcomes in COVID-19 e84919 EN Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Yasushi Tanimoto Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Goro Kimura Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Haruto Yamada Department of Infectious Diseases, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiko Taniguchi Department of Internal Medicine, Fukuyama City Hospital Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: The clinical presentation of coronavirus disease 2019 (COVID-19) ranges from localized respiratory symptoms such as cough and sore throat to systemic symptoms such as fever and fatigue. To our knowledge, no study has assessed severe disease risk by dividing onset symptoms into localized respiratory and other symptoms. We aimed to determine whether the risk of severe COVID-19 differs depending on whether the symptoms at onset are limited to local respiratory symptoms. Method: This was a multicenter prospective cohort study. The patients were classified into localized respiratory or systemic symptom groups based on the symptoms at onset. Demographic data, blood biomarkers, and clinical outcomes, including mortality, intubation, admission to the intensive care unit, and time to discharge, were compared. This study included 100 adult patients diagnosed with COVID-19 between July 2020 and August 2021. Result: Twelve patients were classified into the localized respiratory symptom group and the remaining 88 into the systemic symptom group. No significant differences between the groups were observed in the baseline characteristics, blood biomarkers, or clinical outcomes. The mortality rates were 0.0% and 4.6%, respectively. The median durations to discharge were 11 and 10 days, respectively (p=0.512). The levels of inflammatory and oxidative stress biomarkers, including interleukin-6 and hydroperoxides, were similar between the groups. Conclusion: The symptom type at disease onset was not significantly associated with differences in clinical outcomes. Comprehensive assessments beyond initial symptoms are crucial for predicting disease progression and optimizing management strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer 747 EN Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Kumiko Matsuzaki Division of Hospital Dentistry, Okayama University Hospital Hirotaka Kosaki Division of Hospital Dentistry, Okayama University Hospital Tomoko Kishimoto Division of Hospital Dentistry, Okayama University Hospital Aiko Yoshitomi Division of Hospital Dentistry, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Takashi Makita Department of Pharmacy, Okayama University Hospital Yuta Tanaka Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Surgery, Kawasaki Medical School General Medical Center Background Doxorubicin-cyclophosphamide (AC) and docetaxel-cyclophosphamide (TC) are standard perioperative chemotherapy regimens for breast cancer. Febrile neutropenia (FN) is a common adverse event, and odontogenic infections may contribute to febrile episodes. This study was performed to investigate the incidence and impact of febrile episodes clinically associated with odontogenic infections during AC and TC chemotherapy. Methods A total of 408 patients with breast cancer receiving 4 cycles of AC (n = 285) or TC (n = 123) between 2015 and 2020 were included in this single-center retrospective study. Patients recorded daily axillary temperatures and oral symptoms. Dental evaluations were performed when oral infection was suspected. Febrile episodes (≥ 37.5 °C) were assessed, and their clinical association with odontogenic infections was determined based on dental records and the documented clinical course. Relative dose intensity (RDI) was calculated to assess chemotherapy delivery. Results Overall, 40.2% of patients experienced febrile episodes, and the frequency was higher in the TC group (48.8%) than the AC group (36.5%, P = 0.02). Febrile episodes associated with oral infections occurred in 9.1% of patients, of which 78.4% were clinically associated with odontogenic infections (7.1% of all patients). Most such episodes occurred during the first chemotherapy cycle (79.3%, P < 0.01). Chemotherapy RDI was reduced in three patients with febrile episodes clinically associated with odontogenic infection, but remained ≥ 85%. Conclusions Febrile episodes clinically associated with odontogenic infections occurred in approximately 7%–8% of patients with breast cancer receiving perioperative AC or TC chemotherapy, predominantly during the first cycle. Odontogenic infections should be considered one possible source of febrile episodes during treatment. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-6367 32 4 2026 Spatial Transcriptomics Analysis of Macrophage-to-Myofibroblast Transition in Bronchiolitis Obliterans Following Hematopoietic Stem Cell Transplantation 454 465 EN Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Yusuke Naoi Center for Comprehensive Genomic Medicine, Okayama University Hospital Tomohiro Nagano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saya Kubota Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Kambara Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine Kanako Fujiwara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Terao Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Oyama Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Kunihiro Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Bronchiolitis obliterans (BO) is a severe, fibrotic manifestation of chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Macrophage-derived TGF-β is linked to GVHD-related fibrosis; however, its role in BO remains unclear. Given emerging evidence of macrophage-to-myofibroblast transition (MMT) in fibrosis, this study aimed to investigate whether MMT contributes to BO development. We analyzed lung samples from 3 HSCT recipients with BO who underwent lung transplantation, with tissues from 2 patients with lung cancer as controls. Immunofluorescent staining for CD68, CD206, and α-SMA was used to identify cells undergoing MMT. Spatial transcriptomics was performed to profile gene expression in foamy macrophages across anatomical regions and histological stages, compared to control peribronchiolar regions. Immunostaining showed strong co-expression of CD68, CD206, and α-SMA in foamy macrophages within and surrounding bronchioles in BO samples, with minimal expression in controls, suggesting MMT involvement. In BO, spatial transcriptomics revealed upregulation of macrophage- and TGF-β signaling genes, with distinct stage- and region-specific gene expression patterns. Unsupervised clustering revealed a shift from inflammation to fibrosis. These findings indicate that MMT contributes to fibrosis in BO. Gene expression shifts from inflammation to fibrosis as the disease advances, underscoring the importance of early intervention. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 3 2025 Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study 497 503 EN Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kentaro Tanaka Department of Respiratory Medicine, Kyushu University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Akiko Sato Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Junji Kishimoto Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kuniaki Katsui Department of Radiology, Kawasaki Medical School Kenji Sugio Division of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Background We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented. Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered. Results In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1–85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7–33.5) and 1.4 years [0.69–2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period. Conclusions With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC. Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Determination of the Side Responsible for Bilateral Pneumothorax due to Pleural Communication 225 228 EN Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumi Nakajima Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70859 Simultaneous bilateral spontaneous pneumothorax associated with pleuro-pleural communication is a rare but potentially life-threatening condition, most commonly occurring after major thoracic surgery. We report the case of an 81-year-old man with severe emphysema and a history of esophagectomy who presented with sudden-onset dyspnea. Chest computed tomography revealed bilateral pneumothorax with pleuro-pleural communication. Although bilateral chest tube drainage was performed, the primary side of air leakage could not be identified preoperatively. After induction of general anesthesia, a double-lumen endotracheal tube clamping test identified the right pleural cavity as the source of air leakage, thereby enabling appropriate thoracoscopic surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Oral Eicosapentaenoic Acid and Paclitaxel-Associated Peripheral Neuropathy: A Retrospective Study at Okayama University Hospital 179 184 EN Ayako Morita Center for Clinical Oncology, Okayama University Hospital Hideki Katayama Center for Clinical Oncology, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Original Article /10.18926/AMO/70853 This retrospective study investigated whether eicosapentaenoic acid (EPA) reduces paclitaxel-associated chemotherapy-induced peripheral neuropathy (CIPN) and acute neuropathic pain in dyslipidemic cancer patients. The medical records of cancer patients treated with paclitaxel or nab-paclitaxel at Okayama University Hospital between January 2018 and December 2022 were reviewed. Patients receiving concomitant therapy for dyslipidemia were categorized as EPA users or non-EPA users. Numbness and pain severity were extracted from medical records. The primary endpoint was the change from baseline in Common Terminology Criteria for Adverse Events (CTCAE) grade for peripheral neuropathy and pain; groups were analyzed using the Mann–Whitney U test. Of 184 eligible patients, 18 received EPA. Bleeding events were more frequent in the EPA group; however, changes in numbness and pain did not differ significantly between groups at any time point. Overall, EPA did not show a preventive effect on paclitaxel-associated CIPN or acute neuropathic pain. Future studies should evaluate EPA in combination with other neuroprotective agents to better define its potential role in CIPN prevention. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy 169 178 EN Yuki Nakamura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Takayuki Iwamoto Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Akira Hida Department of Pathology, Matsuyama Shimin Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yuichiro Miyoshi Department of Breast Endocrine Surgery, Kagawa Prefectural Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of General Surgery, Kawasaki Medical School General Medical Center Ryohei Ogata Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yoshikazu Koike Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Tsunehisa Nomura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Katsuhiro Tanaka Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Kazutaka Nakashima Department of General Surgery, Kawasaki Medical School General Medical Center Tomoki Yamatsuji Department of General Surgery, Kawasaki Medical School General Medical Center Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Original Article 10.18926/AMO/70852 The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ρ=0.046, p=0.845; TRB: ρ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2753-670X 41 5 2026 Lung Segmental Perfusion Defect Is Associated With Airway Complications After Living-Donor Lobar Lung Transplantation ivag139 EN Kentaro Imanishi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Ryuko Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences PURPOSE: Airway complications (ACs) are potentially fatal after lung transplantation (LT). Although bronchial blood flow to the graft is supplied mainly from the pulmonary circulation after LT, lung segmental perfusion defects (LSPDs) are occasionally identified on lung perfusion scintigraphy (Q-scinti) after living-donor lobar LT (LDLLT). Lung segmental perfusion defects may impair bronchial healing and contribute to the development of ACs. This study aimed to evaluate the relationship between LSPD and AC after LDLLT. METHODS: We retrospectively reviewed 86 recipients who underwent LDLLT and 163 living donors at our institution from October 1998 to December 2023. Transplanted lungs that developed AC were classified as the AC group, whereas those without AC were classified as the non-AC group. Blood flow in the transplanted lungs was evaluated using Q-scinti after LDLLT. RESULTS: AC developed in 8 (4.9%) of 163 transplanted lungs after LDLLT. Although there were no significant differences in recipient-related variables between the 2 groups, LSPD was detected significantly more frequently in the AC group (n = 8) than in the non-AC group (n = 155) (50.0% vs 6.5%, P = .002). Furthermore, transplanted lungs showing LSPD were associated with significantly higher grades of the pulmonary interlobar fissures at the time of living-donor lobectomy (P = .025). Overall survival did not differ between patients with and without AC after LDLLT. CONCLUSIONS: LSPD on Q-scinti, which may develop in grafts with incomplete interlobar fissures during living-donor lobectomy, is associated with the development of AC after LDLLT. CLINICAL REGISTRATION NUMBER: This study was approved by the Institutional Review Board of Okayama University Hospital (approval date: August 23, 2024; 2409-027). No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan 1 13 EN Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Kozo Yoshimori Department of Clinical Oncology, Japan Anti‐Tuberculosis Association, Fukujuji Hospital Kazuhiko Shibata Department of Medical Oncology, Kouseiren Takaoka Hospital Takeshi Tsuda Division of Respiratory Medicine, Toyama Prefectural Central Hospital Masahiro Seike Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Takahiro Ota Department of Respiratory Medicine, Kyoto City Hospital Koichi Samata Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Pivotal phase 3 trials leading to the approvals of atezolizumab─chemotherapy combinations for non-small cell and extensive-stage small cell lung cancer (NSCLC and ES-SCLC) had strict eligibility criteria. J-TAIL-2 was a prospective, observational study in Japan that evaluated atezolizumab regimens for advanced NSCLC/ES-SCLC, including patients ineligible for global trials. The primary endpoint was 12-month overall survival (OS); safety and efficacy in subgroups defined by age, ECOG PS and/or G8 score, and creatinine clearance were key secondary endpoints. As of February 3, 2023, 1217 patients were treated in clinical practice based on Japanese labeling/treatment guidelines. Patients received atezolizumab with either carboplatin and nab-paclitaxel (atezo + CnP), carboplatin/cisplatin and pemetrexed (atezo + PP), or bevacizumab and carboplatin and paclitaxel (atezo + bev + CP) in the NSCLC cohort (n = 814) or with carboplatin and etoposide (atezo + CE) in the ES-SCLC cohort (n = 403). Overall, 53.5% were ≥ 70 years old, and 11.8% had ECOG PS ≥ 2; median G8 scores were 13 (NSCLC cohort) and 12 (ES-SCLC). Patients < 70 and ≥ 70 years had similar median (m)OS and progression-free survival (mPFS) across treatment regimens. Patients with ECOG PS < 2 and G8 score ≥ median had the highest mOS/PFS vs. patients with ECOG PS ≥ 2 and G8 score<median. Patients ≥ 70 years had higher incidence of Grade ≥ 3 adverse events with atezo + CnP and atezo + PP than patients < 70 years; incidences were similar between groups for other regimens. Older vs. younger patients also had higher incidence of interstitial lung disease. Overall, these results suggest that atezolizumab-containing regimens remain effective in older patients, with no new safety signals. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2 1 13 EN Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasutaka Watanabe Department of Thoracic Oncology, Saitama Cancer Center Nobuyuki Katakami Department of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka Japan Akira Kisohara Department of Respiratory Medicine, Kasukabe Medical Center Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Hirotaka Kuroki Chugai Pharmaceutical Co., Ltd. Masamichi Sugimoto Chugai Pharmaceutical Co., Ltd. Hisao Ashimura Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School J-TAIL-2 evaluated the efficacy and safety of atezolizumab, an anti–programmed death-ligand 1 (PD-L1), plus chemotherapy in patients with non-small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (ES-SCLC) in Japanese clinical practice, demonstrating comparable outcomes to those in the corresponding Phase 3 trials. Although PD-L1 expression is predictive of atezolizumab efficacy in some settings, additional minimally invasive, blood-based biomarkers are needed. This exploratory biomarker study included 359 J-TAIL-2 patients. The NSCLC cohort received atezolizumab combined with carboplatin and nab-paclitaxel (CnP, n = 42), cisplatin/carboplatin and pemetrexed (n = 72), or bevacizumab plus carboplatin and paclitaxel (bev + CP, n = 135). The ES-SCLC cohort received atezolizumab plus carboplatin and etoposide (n = 100). Approximately 560 cancer- or immune-related proteins were evaluated using the Proximity Extension Assay from blood plasma collected at three timepoints: baseline, before the second atezolizumab dose, and at the onset of immune-related adverse events (irAEs). Protein-wise comparisons were made to evaluate significant changes (P < 0.05 and > 0.5 log2 fold change) and linked to clinical outcomes reported in J-TAIL-2. IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev + CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen-dependent in subgroup analyses including older patients and those with EGFR-mutant tumors. These data warrant further investigation across different cancer types and atezolizumab-containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 4 2026 Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017 829 838 EN Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Akihiko Shimomura Department of Breast and Medical Oncology, National Center for Global Health and Medicine Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Takashi Yamanaka Department of Breast Surgery, Kanagawa Cancer Center Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Tomomi Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center Keita Sasaki Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Riku Kajikawa Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Takehiko Sakai Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Yasuaki Sagara Department of Breast Surgery, Sagara Hospital Hideo Shigematsu Department of Breast Surgery, Hiroshima University Hospital Yukinori Ozaki Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Kazuki Nozawa Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Kazuki Sudo Department of Medical Oncology, National Cancer Center Hospital Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Hospital Haruhiko Fukuda Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response. This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer. Methods Patients from JCOG1017, a phase III trial evaluating the role of primary tumor resection, who received primary systemic therapy (PST) were evaluated at three months. In this analysis, treatment response was assessed separately in primary and metastatic sites. Patients were categorized into four groups: discordant I (primary non-PD, metastatic PD), concordant I (both PD), discordant II (primary PD, metastatic non-PD), and concordant II (both non-PD). Results Among 271 patients, overall discordance proportion of treatment response between primary and metastatic sites was 25.1%. Group distribution was 24.7% (discordant I), 9.6% (concordant I), 0.4% (discordant II), and 65.3% (concordant II). Discordance was more frequent in luminal (28.9%), triple-negative (25.0%), and luminal-HER2 (22.0%) subtypes than in HER2-enriched (11.1%). Survival analysis showed prognostic differences: concordant II, with both sites non-PD, demonstrated the most favorable outcome compared with discordant I (HR 0.556; 95% confidence interval, 0.396–0.782). Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 3 2026 Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial 528 536 EN Hideo Shigematsu Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital Tomomi Fujisawa Gunma Prefectural Cancer Center Fumikata Hara Aichi Cancer Center Hiroji Iwata Graduate School of Medical Sciences, Nagoya City University Toshiyuki Ishiba Institute of Science Tokyo Hospital Yukinori Ozaki Cancer Institute Hospital of the Japanese Foundation for Cancer Research Takehiko Sakai Cancer Institute Hospital of the Japanese Foundation for Cancer Research Yasuaki Sagara Hakuaikai Sagara Hospital Akihiko Shimomura National Center for Global Health and Medicine Kazuki Sudo National Cancer Center Hospital Kaori Terata Akita University Hospital Yoichi Naito National Cancer Center Hospital East Kazuki Nozawa Graduate School of Medical Sciences, Nagoya City University Keita Sasaki Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Noriko Mitome Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Taro Shibata Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Okayama University Hospital Purpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors. Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR. Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2–63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20–0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01–4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07–7.93) and III (OR: 4.90; 95% CI: 1.76–13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens. Conclusion ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 4 2026 Immunological effects of amivantamab in EGFR or MET-expressing non-small cell lung cancer 121 EN Ryo Yoshichika Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroko Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Epidermal growth factor receptor (EGFR) mutations represent one of the most frequent oncogenic driver in non-small cell lung cancer (NSCLC). Amivantamab, a bispecific antibody targeting EGFR and MET proto-oncogene, receptor tyrosine kinase (MET), has demonstrated clinical benefit in EGFR-mutant NSCLC through dual blockade, but its immunological role in human clinical specimens, especially tumor-infiltrating lymphocytes (TILs), has not been directly evaluated. Methods We analyzed surgically resected tumor samples from 40 patients with NSCLC to investigate immune responses and their associations with EGFR and MET expression. TILs were characterized by flow cytometry (FCM) and immunohistochemistry (IHC). To assess the immunomodulatory potential of amivantamab, fresh tumor digests containing live tumor cells and TILs were cultured ex vivo with CD3 and CD28 stimulation in the absence or presence of amivantamab, followed by FCM. EGFR and MET expression were also evaluated by IHC. Results EGFR mutations and high EGFR protein expression were associated with a trend toward reduced CD8⁺ T-cell and dendritic cell (DC) infiltration. In ex vivo TIL assays, exposure to amivantamab significantly activated CD8⁺ T cells, such as programmed cell death-1 expression and cytokine production, and promoted DC maturation. These effects were most pronounced in tumors with high EGFR or MET protein expression rather than EGFR mutations. Conclusions This study provides the first direct evidence from ex vivo fresh TIL assays using human NSCLC clinical specimens that amivantamab can activate immune responses. EGFR and MET expression may serve as potential biomarkers for amivantamab-induced immune responses. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-3643 7 3 2026 Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study 100926 EN Masayuki Shirasawa Department of Thoracic Oncology, National Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Tatsuya Yoshida Department of Thoracic Oncology, National Cancer Center Hospital Jumpei Kashima Department of Diagnostic Pathology, National Cancer Center Hospital Masahide Oki Department of Respiratory Medicine, NHO Nagoya Medical Center Hisao Ashimura Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Introduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC. Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry. Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group. Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-2507 37 2026 Robot-assisted pulmonary lobectomy after subtotal esophagectomy in the prone position: A unified port strategy 102295 EN Tomohiro Baba Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 6 2026 A multicenter, randomized, parallel-group confirmatory study protocol to evaluate the efficacy of Soft Protector CPC, a novel oral mucosal protectant, in preventing oral mucositis and alleviating pain in patients with breast cancer e0350803 EN Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Furukawa Department of Dentistry and Oral Surgery, Shikoku Cancer Center Masatoshi Usubuchi Department of Dentistry, Miyagi Cancer Center Tomofumi Hamada Department of Dentistry and Oral Surgery, Sagara Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Yuki Nakatsuka Center for Innovative Clinical Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Oral mucositis is a frequent and debilitating adverse event observed in patients undergoing chemotherapy or radiotherapy. Current management strategies are limited in duration, require frequent application, and fail to address the mechanical irritation from teeth. A novel device, Soft Protector CPC, was developed to overcome these limitations. This multicenter, randomized, two-arm, open-label, confirmatory trial aims to evaluate the efficacy and safety of Soft Protector CPC in patients with breast cancer undergoing chemotherapy. A total of 154 participants will be randomly assigned in a 1:1 ratio to receive either oral care with Soft Protector CPC or oral care alone. The primary endpoint will be oral mucositis as assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 during the comparative treatment period. The secondary endpoints will include CTCAE v3.0 during the continuous treatment period, oral mucositis, pain (CTCAE v5.0), quality of life (Patient Reported Outcomes-CTCAE version 1.0 [PRO-CTCAE v1.0], the 15-item oral health questionnaire of the European Organization For Research And Treatment Of Cancer [EORTC QLQ-OH15], and the pain Numeric Rating Scale), onset and site of mucositis, completion of chemotherapy, use of rescue medications, technical feasibility, and patient preference. The safety endpoints will include adverse events, device malfunction, and laboratory tests. This trial is expected to establish the clinical utility of the Soft Protector CPC for the prevention and management of oral mucositis, with the potential to improve the patients’ quality of life and adherence to cancer therapy. This study was approved by the Clinical Research Review Board and registered with the Japan Registry of Clinical Trials, jRCTs062250005, on April 18, 2025. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0902-0063 40 6 2026 Risk Factors for Waiting List Mortality in Lung Transplant Candidates With Post‐Hematopoietic Stem Cell Transplantation Non‐Infectious Pulmonary Complications e70582 EN Hisao Higo Department of Respiratory Medicine, Okayama University Hospital Satoru Senoo Department of Respiratory Medicine, Okayama University Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Tomohiro Nagano Department of Hematology, Okayama University Hospital Takumi Kondo Department of Hematology, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Respiratory Medicine, Okayama University Hospital Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Nobuaki Miyahara Department of Respiratory Medicine, Okayama University Hospital Background: Late-onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) are a known indication for need of lung transplantation. This study aimed to clarify the clinical characteristics of patients with LONIPCs after HSCT who were registered for lung transplantation and reveal the risk factors for waiting list mortality. Methods: We retrospectively reviewed the clinical data of patients with LONIPCs after allogeneic HSCT who were referred to Okayama University Hospital and registered in the Japan Organ Transplant Network for deceased-donor lung transplantation between 2005 and 2023. Pediatric patients aged <18 years at the time of registration were excluded. Results: Thirty-four patients were included in this study. Notably, two distinct phenotypic groups were identified: One with a bronchiolitis obliterans pattern on high-resolution computed tomography and a mixed ventilatory defect, and the other with a pleuroparenchymal fibroelastosis pattern and a restrictive ventilatory defect. The median waiting duration for a deceased-donor lung transplant was 662 days, and 16 patients died during the waiting period. The cumulative incidence of waiting list mortality was 20.6% (95% confidence interval [CI], 8.9%–35.6%) at 1 year and 46.1% (95% CI, 27.8%–62.7%) at 3 years. A history of pneumothorax, greater dyspnea on exertion, and higher serum Krebs von den Lungen-6 levels were associated with an increased risk of waiting list mortality. Conclusion: In patients with LONIPCs after HSCT, a history of pneumothorax may be a marker of a poor prognosis and could serve as a criterion for referral of lung transplantation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer EN Takuya NISHINA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells EN NANG THEE SU PWINT Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Tailored Management of Anomalous Systemic Arterial Supply to the Basal Segment of the Lung: A Case Report and Literature Review cr.26-0288 EN Shunsuke Mori Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Tomita Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumi Nakajima Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences INTRODUCTION: Parenchyma-preserving strategies for anomalous systemic arterial supply to the basal segment of the lung have gained increasing attention. However, pulmonary infarction of the preserved lung has been reported, and clear criteria for selecting the optimal treatment have yet to be established. We report 2 cases in which detailed preoperative imaging informed tailored management―right posterior basal segmentectomy in 1 patient and endovascular embolization of the aberrant artery in the other―both without postoperative complications. A review of the relevant literature is also provided, with an emphasis on potential selection criteria. CASE PRESENTATION: Case 1: A 20-year-old asymptomatic woman was referred after an abnormal screening chest radiograph. CT demonstrated an aberrant artery arising from the abdominal aorta supplying the right posterior basal segment (S10) with a large intravascular thrombus. The pulmonary artery showed hypoplasia limited to A10, while the other branches were normal, and no parenchymal congestion was identified. Following resection of the aberrant artery, robot-assisted right S10 segmentectomy was performed. The postoperative course was uneventful, and the patient was discharged on POD 6. Case 2: A 27-year-old woman was incidentally diagnosed on CT for an unrelated indication. An aberrant artery arising from the descending thoracic aorta supplied the left basal segment. Pulmonary arterial branches were preserved, with only minimal congestion in S9-10. Angiography revealed no evidence of an arteriovenous fistula. As surgical lung resection was considered unnecessary, coil embolization of the aberrant artery was performed. No complications occurred, and the patient was discharged on day 3 after the procedure. CONCLUSIONS: In patients with anomalous systemic arterial supply to the basal segment of the lung, when pulmonary arterial branches are preserved and background parenchymal congestion is minimal, parenchyma-sparing approaches should be considered. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-3943 7 2 2026 Relationship Between Numbers of Patients Registered and Procedures Performed at Lung Transplantation Centers in Japan 9 EN Takashi Inoue Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Masayuki Chida Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Yoshinori Okada Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University Masaaki Sato Department of Thoracic Surgery, University of Tokyo Hidemi Suzuki Department of General Thoracic Surgery, Chiba University Graduate School of Medicine Yasushi Hoshikawa Department of Thoracic Surgery, Fujita Health University School of Medicine Toyofumi Chen-Yoshikawa Department of Thoracic Surgery, Nagoya University Graduate School of Medicine Daisuke Nakajima Department of Thoracic Surgery, Kyoto University Graduate School of Medicine Yasushi Sintani Department of General Thoracic Surgery, The Osaka University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Toshihiko Sato Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine Takeshi Shiraishi Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine Keitaro Matsumoto Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences Takahiro Nakajima Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Sumiko Maeda Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Background: Recently, there has been a dramatic increase in deceased lung transplantation (DLT) procedures performed in Japan. However, there is concern that the number of transplantations may reach the limit of capacity in some centers. The present study was conducted to analyze the relationship between the numbers of individuals registered for DLT by the Japan Organ Transplantation Network (JOT) and procedures subsequently performed at lung transplantation centers. Methods: Using a database and registry reports provided by the Japanese Society of Lung and Heart-lung Transplantation, the numbers of individuals registered in the JOT and DLT procedures performed from January 2014 to December 2023 were analyzed. Results: The number of registrations was found to be correlated with the number of DLTs, with the coefficient of determination (R2) 0.962 and slope of the regression line (X coefficient) 0.407. The facility with the greatest number of registrations, with a registration-to-transplantation ratio of 0.353, was identified as an outlier (p < 0.05) and excluded from analysis. This exclusion increased both the correlation coefficient value to 0.986 and X coefficient value to 0.461. Conclusions: The present analysis showed that the number of DLTs was well correlated with number of registrations at each of the transplantation facilities. Both registration and transplantation numbers have increased in the recent decade. The facility with the highest number of registrations showed a lower registration-to-transplantation ratio, because the increase in registrations outpaced the number of transplantations. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2051-3380 14 3 2026 An Atypical Surgical Case of Lung Cancer With Unilateral Absence of the Pulmonary Artery, With Only the Superior Branch Remaining e70554 EN Kazuhiro Okada Department of Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of Thoracic Surgery, Okayama University Hospital Tsuyoshi Ryuko Department of Thoracic Surgery, Okayama University Hospital Yasuaki Tomioka Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital A 69-year-old woman was referred to our department for an abnormal shadow on chest radiography. Contrast-enhanced computed tomography (CT) revealed a solid nodule in the right lower lobe and defects in the branches of the middle and lower lobes of the pulmonary artery (PA). Furthermore, collateral circulation had developed via the right internal thoracic, bronchial, intercostal, inferior phrenic, and subdiaphragmatic arteries. The solid nodule was diagnosed as adenocarcinoma by CT-guided biopsy. The day before surgery, embolization was performed using interventional radiology (IVR) to mitigate the risk of bleeding during thoracotomy, resulting in minimal intraoperative bleeding during the subsequent right middle and lower lobectomies with lymph node dissection (ND2a-1). UAPA is a rare congenital abnormality characterized by unilateral pulmonary artery agenesis. The presence of recurrent infections, extensive intrathoracic adhesions, and developed collateral circulation may pose challenges during surgical procedures. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 29 5 2026 Wnt3-mediated fibrosis and carcinogenesis of lung squamous cell carcinoma in idiopathic pulmonary fibrosis 115667 EN Atsushi Matsuoka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Masayoshi Ohki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Hisamatsu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Fujiwara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Ishimura Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Mori Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryunosuke Fujii Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Asuka Mimata Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okada Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Yoshichika Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mao Yoshikawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Fukumoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumi Nakajima Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Inoue Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Idiopathic pulmonary fibrosis (IPF) increases the risk of lung squamous cell carcinoma (LUSC), yet its molecular pathogenesis remains unclear. We conducted multi-omics analysis, including single-cell RNA sequencing and digital spatial profiling, on LUSC specimens from seven patients with usual interstitial pneumonia (UIP). In UIP lung tissue, metaplastic basal cells arising from the transdifferentiation of alveolar type 2 (AT2) cells were increased. LUSC tumors arising within UIP exhibited molecular profiles and trajectory dynamics suggesting derivation from these metaplastic basal cells. Both UIP-affected tissue and associated tumors showed activation of Wnt signaling, particularly WNT3 expression. Additionally, enrichment of the nuclear factor erythroid 2-related factor 2 (NRF2)-linked antioxidant response was observed in LUSC within UIP. Targeting Wnt/β-catenin signaling restored the sensitivity of these stress-adapted cancer cell lines to oxidative damage. These findings suggest that LUSC within UIP originates from AT2-derived metaplastic basal cells and involves aberrant Wnt3 activation, linking fibrosis to carcinogenesis and highlighting a potential therapeutic strategy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery 131 139 EN Shunsuke Nakata Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Fumiaki Takatsu Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Yoshihiro Mikuriya Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Tomokazu Kakishita Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Shinji Hato Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Koji Ohta Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Takaya Kobatake Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Original Article /10.18926/AMO/70455 Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-5345 64 3 2026 Short- and long-term outcomes of anti-thymocyte globulin-based regimen for acute antibody-mediated rejection after lung transplantation 101428 EN Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Shinji Otani Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background: Antibody-mediated rejection (AMR) remains a major barrier to successful lung transplantation (LTx). Despite advances in donor-specific alloantibody (DSA) detection, effective treatments are limited, with current management largely empirical. Acute clinical AMR, marked by rapid graft dysfunction, demands urgent intervention. In Japan, where approved therapies for AMR were historically limited, rabbit anti-thymocyte globulin (rATG) has been adopted as a treatment option. Methods: This retrospective study analyzed 11 patients who developed acute AMR within three months after LTx at Okayama University Hospital between 2013 and 2023. Diagnosis (ISHLT possible AMR) was based on acute graft dysfunction unresponsive to steroids, positive DSA, and exclusion of infection, without histological confirmation due to procedural risk. rATG (1.5 mg/kg/day for 7 days) was administered, along with intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and rituximab when indicated. Outcomes included DSA clearance, clinical response, survival, and adverse events. Results: Remission was achieved in 64% of patients, with 36% not requiring PLEX and 64% not receiving rituximab. Early rATG treatment correlated with favorable outcomes, whereas delayed therapy resulted in poorer responses. Six patients (55%) survived without chronic lung allograft dysfunction (CLAD) for over one year. Adverse events included cytomegalovirus infection (91%), bacterial pneumonia (36%), fungal infection (18%), and malignancy (18%). Conclusions: rATG was effective for acute possible AMR management, particularly when initiated early. Some patients achieved remission without adjunct therapy, indicating rATG's potent immunosuppressive activity. However, frequent infectious complications emphasize the need for optimized dosing and further studies to validate its safety and long-term efficacy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 7 2026 CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer 3143 EN Tiantian Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gakushi Nishida Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1－/－, and Fpr2－/－ mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2－/－ mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2－/－ mice for further studies. Primary tumor growth was comparable between WT and Cxcr2－/－ mice, whereas lung metastasis was significantly increased in Cxcr2－/－ mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2－/－ mice. In vitro, WT, but not Cxcr2－/－, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. No potential conflict of interest relevant to this article was reported.

John Wiley & Sons Ltd. Acta Medica Okayama 2314-6133 2025 2025 Comparing the Activity of Peripheral Blood Mononuclear Cells Frozen Under Electromagnetic Field Freezing and Standard Slow-Freezing 9884345 EN Takehiro Matsubara Okayama University Hospital Biobank Mina Takagi Faculty of Health Sciences, Okayama University Medical School Takahiro Uwabo Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine Shinichi Toyooka Okayama University Hospital Biobank Mizuki Morita Okayama University Hospital Biobank Peripheral blood mononuclear cells (PBMCs) are cells obtained from the blood that are used not only in clinical tests but also in various research applications. The slow-freezing (SLF) method, currently the standard for PBMC cryopreservation, involves extended storage at －80°C before transfer to liquid nitrogen. Delays in this transfer, such as overnight or weekend holds, risk a gradual decline in cell viability. Additionally, variability in freezing duration can lead to inconsistent cell quality, emphasizing the need for an alternative freezing method that allows for more timely transfer to liquid nitrogen. This study is aimed at clarifying whether the method of using a freezer with an applied electromagnetic field (EMF) is superior to the currently used standard SLF method for PBMC cryopreservation. A comparison of the number of viable cells, cell viability, and cell activity showed that the EMF method was equivalent to the SLF method. However, the shortest time required for freezing was significantly shorter with the EMF method than the SLF method (0.25 vs. 3 h), allowing for earlier transfer of PBMC to liquid nitrogen. This demonstrates that the EMF method offers an advantage in operational efficiency, particularly for facilities that routinely process and store PBMCs, such as biobanks and other storage-focused departments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 21 50 2025 Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis e06926 EN Mayu Ohira Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Moe Kitamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyo Iwasaki Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruko Ohta‐Okano Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiyori Tsujii Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reika Nakamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Nakazawa Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akihiro Nishiguchi Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science Masaya Yamamoto Department of Materials Processing, Graduate School of Engineering, Tohoku University Kensuke Osada Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Atsushi Masamune Division of Gastroenterology, Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations EN Yasuhito Kegoya Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryo Mizuta Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryosuke Ikemachi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mako Kamiura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family―such as FGFR::TACC fusions and FGFR1 mutations―have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1757-2215 19 1 2025 Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer 13 EN Anna Rogachevskaya Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Ohtsu Harvard Medical School Vanessa D. Chin UMass Chan Medical School, UMass Memorial Medical Center Tirso Peña Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Seiji Arai Department of Urology, Gunma University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atsushi Fujimura Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University Atsushi Tanaka Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment. Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway. Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 9 6 2025 Surgery for Older Cancer Patients: Cross‐Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee 1128 1136 EN Chie Tanaka Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine Takashi Ofuchi Department of Surgery, Kyushu University Beppu Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Inoue Department of Obstetrics and Gynecology, University of Fukui Ken Sugimoto Department of General Geriatric Medicine, Kawasaki Medical School Keiko Murofushi Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Toru Okuyama Department of Psychiatry/Palliative Care Center, Nagoya City University West Medical Center Shigeaki Watanuki National Center for Global Health and Medicine, National College of Nursing Chiyo Imamura Advanced Cancer Translational Research Institute, Showa University Daisuke Sakai Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine Naomi Sakurai Cancer Solutions Co. Ltd Kiyotaka Watanabe Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University Kazuo Tamura NPO Clinical Hematology/Oncology Treatment Study Group Toshiaki Saeki Breast Oncology Service, Saitama Medical University International Medical Center Hiroshi Ishiguro Breast Oncology Service, Saitama Medical University International Medical Center Background: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients. Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest. Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients. Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 6 2025 Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study e86575 EN Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Naohiro Oda Department of Respiratory Medicine, Okayama University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Tomoki Tamura Department of Respiratory Medicine, Okayama University Hospital Ryo Toyozawa Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Kentaro Tanaka Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Tomonari Sasaki Department of Radiation Oncology, Iizuka Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Junji Kishimoto Center for Clinical and Translational Research, Kyushu University Hospital Kuniaki Katsui Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kenji Sugio Thoracic and Breast Surgery, Oita University Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression. Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients. Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported. Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 1743-9159 112 2 2025 Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis 2301 2310 EN Tatsuya Hayashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center of Innovative Clinical Medicine, Okayama University Hospital Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Habu Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Okayama University Thoracic Surgery Study Group (OUTSSG) Tomoaki Otsuka Okayama University Thoracic Surgery Study Group (OUTSSG) Mototsugu Watanabe Okayama University Thoracic Surgery Study Group (OUTSSG) Takeshi Kurosaki Okayama University Thoracic Surgery Study Group (OUTSSG) Eiji Yamada Okayama University Thoracic Surgery Study Group (OUTSSG) Eisuke Matsuda Okayama University Thoracic Surgery Study Group (OUTSSG) Tatsurou Hayashi Okayama University Thoracic Surgery Study Group (OUTSSG) Toshiya Fujiwara Okayama University Thoracic Surgery Study Group (OUTSSG) Makio Hayama Okayama University Thoracic Surgery Study Group (OUTSSG) Hiroyuki Tao Okayama University Thoracic Surgery Study Group (OUTSSG) Masaomi Yamane Okayama University Thoracic Surgery Study Group (OUTSSG) Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group (OUTSSG) Yuji Hirami Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiro Washio Okayama University Thoracic Surgery Study Group (OUTSSG) Takahiko Misao Okayama University Thoracic Surgery Study Group (OUTSSG) Motohiro Yamashita Okayama University Thoracic Surgery Study Group (OUTSSG) Yoshifumi Sano Okayama University Thoracic Surgery Study Group (OUTSSG) Masao Nakata Okayama University Thoracic Surgery Study Group (OUTSSG) Osamu Kawamata Okayama University Thoracic Surgery Study Group (OUTSSG) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear. Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors. Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group. Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 2473-4276 9 2025 Development and Validation of an Ipsilateral Breast Tumor Recurrence Risk Estimation Tool Incorporating Real-World Data and Evidence From Meta-Analyses: A Retrospective Multicenter Cohort Study e2500182 EN Yasuaki Sagara Department of Breast and Thyroid Surgical Oncology, Hakuaikai Sagara Hospital Atsushi Yoshida Department of Breast Surgical Oncology, St Luke's International Hospital Yuri Kimura Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Yuka Ono Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Koji Takada Department of Breast Surgical Oncology, Osaka Metropolitan University Graduate School of Medicine Yuri Ito Department of Medical Statistics, Osaka Medical and Pharmaceutical University Tomo Osako Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research Takehiko Sakai Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR Purpose Ipsilateral breast tumor recurrence (IBTR) remains a critical concern for patients undergoing breast-conserving surgery (BCS). Reliable risk estimation tools for IBTR risk can support personalized surgical and adjuvant treatment decisions, especially in the era of evolving systemic therapies. We aimed to develop and validate models to estimate IBTR risk. Patients and Methods This multicenter retrospective cohort study included 8,938 women who underwent partial mastectomy for invasive breast cancer between 2008 and 2017. Prediction models were developed using Cox proportional hazards regression and validated via bootstrap resampling. Model performance was assessed using Harrell's C-index, Brier scores, calibration plots, and goodness-of-fit tests. Results During a median follow-up of 9.0 years (IQR, 6.6-10.9), IBTR occurred in 320 patients (3.6%). The initial model, based on variables from Sanghani et al, achieved a Harrell's C-index of 0.74. Incorporating hormonal receptor status, human epidermal growth factor receptor 2 status, radiotherapy, and targeted therapy as predictors reduced the C-index to 0.65, despite their clinical relevance. Importantly, the inclusion of these factors improved calibration, demonstrating better alignment between predicted and observed IBTR probabilities. Although the hazard ratios (HRs) for radiotherapy aligned with the Early Breast Cancer Trialists’ Collaborative Group meta-analyses (MA), those for chemotherapy and endocrine therapy showed slight differences. Therefore, HRs from the MA were used to represent treatment effects in our model. Conclusion We have developed and internally validated a new risk estimation model for IBTR using Cox regression and bootstrap methods. A Web-based risk estimation tool is now available to facilitate individualized risk assessment and treatment planning. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Genotype–Phenotype Correlations of Li–Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort EN Fumito Yamazaki Department of Pediatrics, Keio University School of Medicine Yoshiko Nakano Department of Genetic Medicine and Services, National Cancer Center Hospital Masashi Sanada Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center Hiroki Kurahashi Division of Molecular Genetics, Center for Medical Science, Fujita Health University Shunsuke Miyai Division of Molecular Genetics, Center for Medical Science, Fujita Health University Arisa Ueki Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Yuko Watanabe Department of Pediatric Oncology, National Cancer Center Hospital Daisuke Hasegawa Department of Pediatrics, St. Luke's International Hospital Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko M. Saito Clinical Research Center, NHO Nagoya Medical Center Eisuke Inoue Showa Medical University Research Administration Center, Showa Medical University Motohiro Kato Department of Pediatrics, The University of Tokyo Hiroyoshi Hattori Department of Clinical Genetics, NHO Nagoya Medical Center Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term “attenuated LFS” has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as “LFS” in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype–phenotype correlations in several respects. UMIN-CTR: UMIN000045855. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2) EN Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Ichiro Yoshino International University of Health and Welfare, Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasutaka Watanabe Department of Thoracic Oncology, Saitama Cancer Center Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Akira Kisohara Department of Respiratory Medicine, Kasukabe Medical Center Shoichi Kuyama Department of Respiratory Medicine, NHO Iwakuni Clinical Center Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Asako Miwa Chugai Pharmaceutical Co., Ltd. Shunichiro Iwasawa Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n = 217; atezo + PP, n = 211; atezo + bev + CP, n = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 6 2025 Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer 1405 1416 EN Takuya Nishina Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Maki Tanioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenji Takada Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2405-6316 36 2025 A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease 100857 EN Hideaki Hirashima Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Yukinori Matsuo Department of Radiation Oncology, Kindai University Faculty of Medicine Satoshi Ishikura Department of Radiation Oncology, St. Luke’s International Hospital, St. Luke’s International University Mitsuhiro Nakamura Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University Ikuno Nishibuchi Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University Daisuke Kawahara Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University Yoshihisa Shimada Department of Surgery, Tokyo Medical University Yoshiro Nakahara Department of Respiratory Medicine, Kitasato University Hospital Teiji Nishio Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Naoto Shikama Department of Radiation Oncology, Juntendo University Graduate School of Medicine Shun-ichi Watanabe Department of Thoracic Surgery, National Cancer Center Hospital Isamu Okamoto Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Takashi Mizowaki Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach. Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity–gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing. Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case. Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 呼吸器外科領域におけるロボット支援手術の進化と展望 132 136 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 令和６年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 95 97 EN Shinichi Kawana Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2059-7029 10 11 2025 Association between adjuvant chemotherapy and outcomes in resected locoregional recurrence of hormone receptor-positive HER2-negative breast cancer: a multi-institutional retrospective study 105889 EN Y. Ozaki Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research E. Tokuda Department of Medical Oncology, Fukushima Medical University Y. Sagara Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital F. Hara Department of Breast Oncology, Aichi Cancer Center Hospital S. Sasada Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University M. Sawaki Department of Breast Oncology, Aichi Cancer Center Hospital C. Kanbayashi Department of Breast Oncology, Niigata Cancer Center Hospital T. Yamanaka Department of Breast Surgery and Oncology, Kanagawa Cancer Center T. Onishi Department of Breast Oncology, National Cancer Center Hospital East Y. Fujiki Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital A. Suto Department of Breast Oncology, National Cancer Center Hospital Y. Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital E. Tokunaga Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center T. Aruga Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital R. Nakamura Division of Breast Surgery, Chiba Cancer Center T. Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center S. Saji Department of Medical Oncology, Fukushima Medical University H. Iwata Department of Advanced Clinical Research and Development, Nagoya City University T. Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background: To evaluate the association of adjuvant chemotherapy and prognosis for locoregional recurrence (LRR) in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative subtype breast cancer. Patients and methods: We carried out a multi-institutional retrospective cohort study in patients with breast cancer who developed HR-positive HER2-negative LRR. Patients who underwent curative surgery for LRR between 2014 and 2018 were categorized based on whether they received adjuvant chemotherapy for LRR (CTx versus no-CTx). Invasive disease-free survival (iDFS) was evaluated between the groups by Cox proportional hazards analysis. The primary analysis used a double-robust Cox model incorporating inverse probability of treatment weighting, and a sensitivity analysis using propensity score matching was also carried out. Results: A total of 958 patients were included. The median time from the primary surgery to LRR diagnosis was 9.5 years (interquartile range 3.1-10.1 years). There were 235 patients (25%) in the CTx group and 722 (75%) in the no-CTx group. Among all patients, the 5-year iDFS rate was 75.4% [95% confidence interval (CI) 72.4% to 78.2%]. Multivariate analysis showed better iDFS in the CTx group (hazard ratio 0.70, 95% CI 0.49-0.99, P = 0.045). Sensitivity analysis supported these findings. Subgroup analyses showed that the CTx group had better iDFS in cases with non-ipsilateral breast tumor recurrence (IBTR), recurrences during adjuvant endocrine therapy for primary breast cancer, and without perioperative chemotherapy for primary breast cancer. Secondary analysis showed no significant difference with a worse trend toward overall survival in the CTx group with multivariate Cox proportional hazards analysis. Conclusion: Adjuvant chemotherapy for HR-positive HER2-negative LRR was associated with better iDFS, particularly in cases of non-IBTR, recurrences during adjuvant endocrine therapy, and no prior perioperative chemotherapy for their primary tumor. However, the retrospective design and inability to distinguish true recurrences from new primary tumors in IBTR warrant cautious interpretation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3642 8 1 2025 Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma 1773 EN Atsushi Matsuoka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Masayoshi Ohki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Hisamatsu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Fujiwara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Ishimura Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryunosuke Fujii Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Higashihara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naohiro Hayashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okada Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Yoshichika Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumiaki Mukohara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mao Yoshikawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Fukumoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Otani Department of Pathology, Beth Israel Deaconess Medical Center Atsushi Tanaka Department of Pathology, Beth Israel Deaconess Medical Center Hirofumi Inoue Center for Comprehensive Genomic Medicine, Okayama University Hospital Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 5 2025 Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors 547 555 EN Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Naomi Kiyota Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kyoko Kato Department of Medical Oncology, National Hospital Organization Nagoya Medical Center Kaoru Kubota Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Akinobu Nakata Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiya Narita Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Kojiro Shimozuma Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University Kei Muro Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Tetsuya Iwamoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Yuki Takumoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takeru Shiroiwa Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takashi Fukuda Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takuhiro Yamaguchi Division of Biostatistics, Tohoku University Graduate School of Medicine Yasuhiro Hagiwara Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine Hironobu Minami Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 12 2025 Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) 1584 1595 EN Satoshi Kobayashi Department of Gastroenterology, Kanagawa Cancer Center Kohei Nakachi Department of Medical Oncology, Tochigi Cancer Center Kouji Yamamoto Department of Biostatistics, Yokohama City University School of Medicine Makoto Ueno Department of Gastroenterology, Kanagawa Cancer Center Yuta Maruki Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Takeshi Terashima Department of Gastroenterology, Kanazawa University Hospital Satoshi Shimizu Department of Gastroenterology, Kanazawa University Hospital Kotoe Oshima Division of Gastrointestinal Oncology, Shizuoka Cancer Center Kunihiro Tsuji Department of Gastroenterology, Ishikawa Prefectural Central Hospital Yoshiharu Masaki Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine Hidetaka Tsumura Department of Gastroenterological Oncology, Hyogo Cancer Center Taro Shibuki Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East Masato Ozaka Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research Naohiro Okano Department of Medical Oncology, Kyorin University Faculty of Medicine Yukiyasu Okamura Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine Kumiko Umemoto Department of Clinical Oncology, St. Marianna University School of Medicine Tatsunori Satoh Department of Gastroenterology, Shizuoka General Hospital Yasushi Kojima Department of Gastroenterology, National Center for Global Health and Medicine Kazuhiko Shioji Department of Gastroenterology, Niigata Cancer Center Hospital Hiroko Nebiki Department of Gastroenterology, Osaka City General Hospital Toshifumi Doi Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Atsushi Naganuma Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center Shigeki Kataoka Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University Emiri Kita Department of Gastroenterology, Chiba Cancer Center Hiroyuki Asama Department of Gastroenterology, Fukushima Medical University Kaoru Tsuchiya Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital Michiaki Unno Department of Surgery, Tohoku University Graduate School of Medicine Reiko Ashida Second Department of Internal Medicine, Wakayama Medical University Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Graduate School of Medicine Izumi Ohno Department of Gastroenterology, Chiba University Graduate School of Medicine Takao Itoi Department of Gastroenterology, Tokyo Medical University Yuji Negoro Department of Oncologial Medicine, Kochi Health Sciences Center Yasunari Sakamoto Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital Shiho Arima Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences Akinori Asagi Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center Hiroyuki Okuyama Department of Medical Oncology, Kagawa University Hospital Yoshito Komatsu Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center Noritoshi Kobayashi Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University Hiroaki Nagano Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine Junji Furuse Department of Gastroenterology, Kanagawa Cancer Center Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC. Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups. Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49). Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 23 2025 A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion 3413 3418 EN Takahiro Baba Department of Respiratory Medicine, Okayama University Hospital Hirofumi Inoue Department of Medical Support, Okayama University Hospital Hiromi Matsuoka Department of Medical Support, Okayama University Hospital Mio Kyakuno Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine Yusuke Yoshinaga Department of Respiratory Medicine, Okayama University Hospital Tetsuya Takeguchi Department of Respiratory Medicine, Okayama University Hospital Miho Fujiwara Department of Respiratory Medicine, Okayama University Hospital Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Eri Nakamura Department of Respiratory Medicine, Okayama University Hospital Ayako Morita Department of Respiratory Medicine, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisao Higo Department of Respiratory Medicine, Okayama University Hospital Masanori Fujii Department of Geriatric Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Comparative Analysis of a Dual DNA–RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database EN Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mashu Futagawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Next-generation sequencing-based comprehensive cancer genomic profiling is promising in cancer management; however, most studies rely on tumor-only DNA panels from single institutions. In 2023, Japan introduced an insurance-covered cancer genomic profiling test―the GenMine TOP Cancer Genome Profiling System―a dual DNA–RNA panel with matched tumor–normal testing. This study evaluated its utility compared to a conventional DNA-only test (FoundationOne CDx) in managing sarcoma patients using a nationwide genetic profiling database provided by the Center for Cancer Genomics and Advanced Therapeutics. This study included 1046 patients registered between August 2023 and October 2024. The dual DNA–RNA test identified significantly more fusion genes (20.3% vs. 7.4%, p < 0.001) and therapeutically targetable kinase fusions (3.5% vs. 1.2%, p = 0.019) than the DNA-only test. Among patients with translocation-related sarcomas, histology-specific fusion genes were identified in 77.5% using the dual panel, compared to 40.0% with the DNA-only panel (p < 0.001). In non-gastrointestinal stromal tumor sarcomas, the dual test showed a trend toward higher rates of genotype-matched therapy (4.3% vs. 2.6%, p = 0.25) and a significantly higher rate of molecular targeted therapy (4.3% vs. 1.5%, p = 0.03). Additionally, 5.7% of patients had pathogenic germline variants identified through tumor–normal matched analysis. These findings suggest that a dual DNA–RNA panel with matched tumor–normal testing may improve diagnostic accuracy and inform treatment decisions in the routine clinical management of sarcoma. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 1109-6535 22 6 2025 C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma 836 849 EN ATSUSHI TANAKA Department of Pathology, Beth Israel Deaconess Medical Center YUSUKE OTANI Department of Pathology, Beth Israel Deaconess Medical Center MASAKI MAEKAWA Department of Pathology, Beth Israel Deaconess Medical Center ANNA ROGACHEVSKAYA Department of Pathology, Beth Israel Deaconess Medical Center TIRSO PEÑA Department of Pathology, Beth Israel Deaconess Medical Center VANESSA D. CHIN UMass Chan Medical School, UMass Memorial Medical Center SHINICHI TOYOOKA Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MICHAEL H. ROEHRL Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI FUJIMURA Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC. Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines. Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways. Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 20 2025 Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells 10072 EN Nang Thee Su Pwint Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein–protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF–SPRED2 axis in BC progression and highlight it as a potential therapeutic target. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation 329 337 EN Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review /10.18926/AMO/69433 Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1573-7209 28 4 2025 Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma 51 EN May Wathone Oo Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hikita Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoha Mashima Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kosuke Torigata School of Medicine, Kobe University Yin Min Thu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Sachio Ito Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Nakayama Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1071-2690 2025 S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation EN Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Xu Yang Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Bo Pan The First Affiliated Hospital, Zhejiang University School of Medicine Fangping Wu School of Pharmaceutical Sciences, Zhejiang Chinese Medical University Xu Zhang Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine Kazumi Sagayama Faculties of Educational and Research Management Field, Okayama University Bei Sun Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC. No potential conflict of interest relevant to this article was reported.

Universitas Airlangga Acta Medica Okayama 2716-0920 34 2 2024 Depletion of Lysyl Oxidase-Like 4 (LOXL4) Attenuates Colony Formation in vitro and Collagen Deposition in vivo Breast Cancer Model 67 73 EN Ni Luh Gede Yoni Komalasari Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University I Gde Haryo Ganesha Department of Histology, Faculty of Medicine, Udayana University I Gusti Nyoman Sri Wiryawan Department of Histology, Faculty of Medicine, Udayana University Nahoko Tomonobu Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University Background: Lysyl oxidase (LOX) family proteins have recently become a topic in cancer progression. Our recent study found a high expression of LOX-like 4 (LOXL4) in MDA-MB-231 cells. Objective: To reveal the impact of depleted LOXL4 in both in vitro and in vivo breast cancer models from a histological perspective. Material and Method: Endogenous LOXL4 was depleted using the CRISPR/Cas9 on MDA-MB-231 parental cells. Based on the LOXL4 protein expression, the clone was determined for the next experiment, thus generating MDA-MB-231 LOXL4 KO. Cell assay was conducted using colony formation assay (n=3) followed by crystal violet staining. The indicated cells were inoculated orthotopically to female BALB/c nude mice (n=5). At the end of the experiment, tumors were isolated, fixed, and prepared for Masson Trichrome staining. Result: CRISPR/Cas9 completely depleted LOXL4 expression on clone number #2-22. Depletion of LOXL4 reduced the colony size formed by MDA-MB-231 cells. MDA-MB-231 LOXL4 KO #2-22 derived tumors showed depressed tumor volume compared to the parental group. Reduced collagen was also observed from the Masson Trichrome staining (p<0.001). Conclusion: Depletion of LOXL4 downregulates the growth of MDA-MB-231 cells in vitro and collagen deposition in vivo. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 14 2025 Definitions of, Advances in, and Treatment Strategies for Breast Cancer Oligometastasis 2406 EN Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yuki Fujiwara Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Kosaka Department of Breast and Endocrine Surgery, Okayama University Hospital Yuki Narahara Department of Breast and Endocrine Surgery, Okayama University Hospital Kento Fujii Department of Breast and Endocrine Surgery, Okayama University Hospital Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Shutaro Kato Department of Breast and Endocrine Surgery, Okayama University Hospital Asuka Mimata Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Chihiro Kuwahara Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Maki Tanioka Department of Breast and Endocrine Surgery, Okayama University Hospital Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 2025 Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial EN Tadahiko Shien Okayama University Hospital Fumikata Hara Cancer Institute Hospital Kenjiro Aogi National Hospital Organization Shikoku Cancer Center Yasuhiro Yanagida Shizuoka General Hospital Michiko Tsuneizumi Gunma Prefectural Cancer Center Naohito Yamamoto Chiba Prefectural Cancer Center Hiroshi Matsumoto Saitama Prefectural Cancer Center Akihiko Suto National Cancer Center Hospital Kenichi Watanabe Hokkaido Cancer Center Michiko Harao Jichi Medical University Hospital Chizuko Kanbayashi Niigata Prefectural Cancer Center Mitsuya Itoh Hiroshima City Hiroshima Citizen’s Hospital Takayuki Kadoya Hiroshima University Hospital Keisei Anan Kitakyushu Municipal Medical Center Shigeto Maeda Nagasaki Municipal Medical Center Keita Sasaki National Cancer Center Hospital Gakuto Ogawa National Cancer Center Hospital Shigehira Saji Fukushima Medical University Haruhiko Fukuda National Cancer Center Hospital Hiroji Iwata Aichi Cancer Center Hospital Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients. Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS). Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths. Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy. Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 4 2025 Immediate breast reconstruction surgery for breast cancer: current status and future directions 630 637 EN Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroko Nogi Department of Breast and Endocrine Surgery, The Jikei University School of Medicine Akiko Ogiya Department of Breast Surgery, Japanese Red Cross Medical Center Makoto Ishitobi Department of Breast Surgery, Mie University School of Medicine Chikako Yamauchi Department of Radiation Oncology, Shiga General Hospital Ayaka Shimo Department of Breast and Endocrine Surgery, St. Marianna University School of Medicine Kazutaka Narui Department of Breast and Thyroid Surgery, Medical Center, Yokohama City University Naomi Nagura Department of Breast Surgical Oncology, St Luke’s International Hospital Hirohito Seki Department of Breast Surgery, Kyorin University School of Medicine Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Miho Saiga Department of Plastic Surgery, Okayama University Hospital Tatsuya Uchida Department of Plastic Surgery, Okayama University Hospital Shinsuke Sasada Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Teruhisa Sakurai Sakurai Breast Clinic Naoki Niikura Department of Breast Oncology, Tokai University School of Medicine Hiroki Mori Department of Plastic and Reconstructive Surgery, Tokyo Medical and Dental University Background Immediate breast reconstruction (IBR) has become increasingly recognized in Japan as an important component of breast cancer care, improving patients’ quality of life after mastectomy. While the adoption of IBR is growing, the reconstruction rate in Japan remains lower than in Western countries. To clarify the current practice and challenges, the Japanese Breast Cancer Society (JBCS) conducted a nationwide survey. Methods We conducted a comprehensive web-based questionnaire survey among all JBCS-certified institutions between December 2020 and February 2021. The survey assessed institutional capabilities, surgical techniques, decision-making criteria for BR, and the integration of adjuvant therapy. Results A total of 429 institutions responded, with 72.5% offering BR and 61.7% capable of providing immediate reconstruction. Nipple-sparing mastectomy (NSM) was performed at 73.7% of institutions offering reconstruction. Multidisciplinary conferences with plastic surgeons were held at 70.5% of institutions. Approximately 30% of institutions discontinued IBR if sentinel lymph node metastases were detected intraoperatively, and 62.8% avoided recommending IBR for patients likely to require postoperative radiation therapy. In 94% of institutions, BR did not cause delays in the administration of adjuvant chemotherapy. However, 15% of institutions modified their radiation therapy approach in reconstructed patients. Additionally, 27% of physicians still believed that BR could negatively affect prognosis. Conclusions The survey confirmed that IBR is widely performed and feasible in Japan. However, institutional differences, limited access to plastic surgeons, and persistent misconceptions remain significant barriers. Strengthening multidisciplinary collaboration and establishing standardized guidelines will help improve BR rates and patient outcomes in Japan. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2950-1334 8 2025 Downward hyperinflation of the native lung after right single lung transplantation for COPD: A case report highlighting diaphragmatic mobility 100268 EN Shin Tanaka Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Ryuko Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences A 60-year-old male with COPD underwent right single lung transplantation. Despite progressive hyperinflation of the native left lung, the transplanted lung maintained function, as downward expansion of the left lung displaced the diaphragm without compressing the mediastinum. This suggests diaphragm mobility, aided by the absence of the liver beneath the left diaphragm, contributes to favorable outcomes in right single lung transplantation by preventing mechanical compression of the transplanted lung. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2753-670X 38 2 2024 Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation ivae021 EN Toshio Shiotani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Yasuaki Tomioka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kazuhiko Shien Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Hiromasa Yamamoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. METHODS: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0–1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml. CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 The Work Productivity of Cancer-survivor and Non-cancer-survivor Workers 243 251 EN Mika Kamano Department of Public Health, Faculty of Medicine, Kagawa University Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Nlandu Roger Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Akitsu Murakami Cancer Center, Kagawa University Hospital Yusuke Yamadori Department of Anesthesiology, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/69149 We investigated the work productivity levels of employed cancer survivors and non-cancer-survivor workers by conducting a cross-sectional study in Japan between February and March 2019, using an online survey. A total of 561 employed individuals aged 20-64 years were analyzed. Work productivity was assessed using the Work Productivity and Activity Impairment-General Health questionnaire which evaluates absenteeism, presenteeism, and overall work productivity loss. The questionnaire responses demonstrated that the cancer survivors within 1 year of diagnosis had significantly higher absenteeism compared to the non-cancer workers (p=0.048). Although presenteeism and overall work productivity loss were also higher in the non-cancer-survivor group, the differences were not significant. Cancer survivors within 1 year of diagnosis exhibited higher absenteeism, but their work productivity appeared to recover to levels comparable to those of the non-cancer workers over time. These findings may contribute to workplace policies supporting cancer survivors’ return to work. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7634 14 15 2025 Real‐World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcoma e71098 EN Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuto Itano Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mashu Futagawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsunori Shimoi Department of Medical Oncology, National Cancer Center Hospital Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Hirasawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiro Tabata Center for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA–RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment. Patients and Methods: In this study, three types of DNA panel and one DNA–RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies. Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA–RNA panel identified more histology-specific fusion genes than DNA panels (p = 0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p = 0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin. Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA–RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 2025 Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer EN Yoshie Maki Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Ozato Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Kenta Hamada Faculty of Medicine, Department of Practical Gastrointestinal Endoscopy, Dentistry and Pharmaceutical Sciences, Okayama University Masaya Iwamuro Department of Gastroenterology, Okayama University Hospital Seiji Kawano Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Motoyuki Otsuka Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Background The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear. Methods We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes. Results In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status. Conclusion HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-0836 638 8049 2025 Immune evasion through mitochondrial transfer in the tumour microenvironment 225 236 EN Hideki Ikeda Division of Cell Therapy, Chiba Cancer Center Research Institute Katsushige Kawase Division of Cell Therapy, Chiba Cancer Center Research Institute Tatsuya Nishi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomofumi Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keizo Takenaga Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute Takashi Inozume Division of Cell Therapy, Chiba Cancer Center Research Institute Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Aki Division of Nutriomics and Oncology, RCAST, The University of Tokyo Jason Lin Division of Cell Therapy, Chiba Cancer Center Research Institute Shusuke Kawashima Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichiro Suzuki Department of Medical Oncology, Kindai University Faculty of Medicine Hideki Makinoshima Tsuruoka Metabolomics Laboratory, National Cancer Center Makiko Itami Department of Surgical Pathology, Chiba Cancer Center Yuki Nakamura Division of Cell Therapy, Chiba Cancer Center Research Institute Yasutoshi Tatsumi Division of Cell Therapy, Chiba Cancer Center Research Institute Yusuke Suenaga Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute Takao Morinaga Division of Cell Therapy, Chiba Cancer Center Research Institute Akiko Honobe-Tabuchi Department of Dermatology, Faculty of Medicine, University of Yamanashi Takehiro Ohnuma Department of Dermatology, Faculty of Medicine, University of Yamanashi Tatsuyoshi Kawamura Department of Dermatology, Faculty of Medicine, University of Yamanashi Yoshiyasu Umeda Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yasuhiro Nakamura Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yukiko Kiniwa Department of Dermatology, Shinshu University School of Medicine Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Jun-ichiro Ikeda Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University Toyoyuki Hanazawa Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Mano Division of Cellular Signalling, National Cancer Center Research Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Tsuyoshi Osawa Division of Nutriomics and Oncology, RCAST, The University of Tokyo Masahito Kawazu Division of Cell Therapy, Chiba Cancer Center Research Institute Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 1179-1322 17 2025 Predictive Value of Tumor ERCC1 Expression for Treatment Outcomes After Adjuvant Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer 1477 1486 EN Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Shinsuke Saisho Department of General Thoracic Surgery, Kawasaki Medical School Junichi Soh Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroshige Nakamura Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Tottori University Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Date Department of Thoracic Surgery, Kyoto University Graduate School of Medicine Purpose: To evaluate the predictive value of tumor expression of the excision repair cross-complementation group 1 gene (ERCC1) for the treatment outcomes after platinum-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). Methods: In this study, we conducted immunohistochemical analysis using a mouse monoclonal anti-ERCC1 antibody (clone 8F1) of operative specimens obtained from 238 patients enrolled in the SLCG0401 study which compared paclitaxel plus carboplatin (CBDCA+PTX) with uracil-tegafur (UFT) as adjuvant chemotherapy for stage IB-IIIA NSCLC. The overall survival (OS) of the patients was compared according to the ERCC1 expression status and adjuvant chemotherapy employed. Results: Of the 238 specimens, 102 (42.9%) showed a positive result for ERCC1 expression. There were no significant differences in the patient characteristics or OS between the tumor ERCC1-positive and -negative patient groups. Among the patients with ERCC1-negative tumors, there was no significant difference in the survival between patient groups treated with CBDCA+PTX and UFT (HR=0.932, 95% CI: 0.52– 1.67, p=0.814). However, among the patients with ERCC1-positive tumors, CBDCA+PTX treatment tended to yield an inferior outcome, in terms of the OS, as compared with UFT treatment (HR=1.852, 95% CI: 0.92– 3.73, p=0.080). Multivariate analysis showed that ERCC1 expression was not an independent predictor of the OS following CBDCA+PTX treatment in completely resected NSCLC patients. Conclusion: In completely resected NSCLC patients with positive tumor ERCC1 expression, adjuvant CBDCA+PTX treatment tended to yield an inferior outcome as compared with UFT treatment in terms of the OS. However, immunohistochemical analysis with the 8F1 antibody cannot be used for clinical decision making at this point. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 3 2025 Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 1201 79 EN Junichi Soh Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenicehi Gemba Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terasaki Department of Respiratory Surgery, Saga Medical Center Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center Masaaki Inoue Department of Thoracic Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Yuta Takahashi Department of Thoracic Surgery, Okayama University Hospital Hidejiro Torigoe Department of Thoracic Surgery, Okayama University Hospital Hiroki Sato Department of Thoracic Surgery, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Managing elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-4975 120 1 2025 Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study 87 98 EN Tsuyoshi Ryuko Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group Toshiya Fujiwara Okayama University Thoracic Surgery Study Group Mototsugu Watanabe Okayama University Thoracic Surgery Study Group Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group Takahiko Misao Okayama University Thoracic Surgery Study Group Hidejiro Torigoe Okayama University Thoracic Surgery Study Group Kazuhiro Washio Okayama University Thoracic Surgery Study Group Hiroyuki Tao Okayama University Thoracic Surgery Study Group Daisuke Okutani Okayama University Thoracic Surgery Study Group Makio Hayama Okayama University Thoracic Surgery Study Group Masashi Uomoto Okayama University Thoracic Surgery Study Group Eiji Yamada Okayama University Thoracic Surgery Study Group Shinji Otani Okayama University Thoracic Surgery Study Group Takeshi Kurosaki Okayama University Thoracic Surgery Study Group Yuji Yaginuma Okayama University Thoracic Surgery Study Group Eito Niman Okayama University Thoracic Surgery Study Group Osamu Kawamata Okayama University Thoracic Surgery Study Group Hitoshi Nishikawa Okayama University Thoracic Surgery Study Group Tomoaki Otsuka Okayama University Thoracic Surgery Study Group Takeshi Yoshikawa Okayama University Thoracic Surgery Study Group Tatsuro Hayashi Okayama University Thoracic Surgery Study Group Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited. Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score–adjusted cohorts. Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score–adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence. Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1071-2690 60 10 2024 Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells 1215 1227 EN Masakiyo Sakaguchi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Rie Kinoshita Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nahoko Tomonobu Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Sakaguchi Department of Microbiology, Tokushima Bunri University Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Hitoshi Murata Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ken-ichi Yamamoto Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tetta Takahashi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuma Gohara Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiki Ochi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Fan Jiang Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ni Luh Gede Yoni Komalasari Faculty of Medicine, Udayana University Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine I Made Winarsa Ruma Faculty of Medicine, Udayana University I Wayan Sumardika Faculty of Medicine, Udayana University Jin Zhou Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology Tomoko Honjo Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Kazumi Sagayama Organization for Research and Innovation Strategy, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Eisaku Kondo Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1201-9712 156 2025 Recurrent diffuse panbronchiolitis after lung transplantation: Off-label use of inhaled tobramycin for Pseudomonas aeruginosa control in a transplant recipient 107913 EN Shin Tanaka Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tuyoshi Ryuko Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Mikio Okazaki Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: This report highlights a clinical case of recurrent diffuse panbronchiolitis (DPB) after bilateral lung transplantation (LTx), with a focus on the therapeutic impact of off-label inhaled tobramycin solution for inhalation (TSI) in managing Pseudomonas aeruginosa colonization. Methods: A Japanese woman with a history of DPB experienced disease recurrence following bilateral LTx. Persistent colonization by P. aeruginosa and recurrent respiratory symptoms were observed. Off-label TSI therapy, commonly used in cystic fibrosis, was introduced. Clinical response was assessed through radiologic imaging, bronchoscopy, and microbiological cultures. Results: TSI administration led to significant clinical and radiological improvement. P. aeruginosa was eradicated from sputum cultures within one month and remained absent throughout six months of follow-up. No hospitalizations or adverse events were reported during therapy. Conclusion: This case suggests the potential of TSI as a therapeutic approach for managing recurrent DPB and indicates its role in stabilizing post-transplant outcomes. Further studies may clarify its efficacy and expand its application in broader DPB management strategies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-1683 73 2025 Incidence, Management, and Prevention of Gynecomastia and Breast Pain in Patients with Prostate Cancer Undergoing Antiandrogen Therapy: A Systematic Review and Meta-analysis of Randomized Controlled Trials 31 42 EN Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Robert J. Schulz Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Ekaterina Laukhtina Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Koichiro Wada Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Pierre I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Background and objective: In patients with prostate cancer treated with antiandrogen monotherapy, gynecomastia and breast pain are relatively common. In the setting of androgen receptor pathway inhibitors (ARPIs), the incidence of these adverse events (AEs) remains unclear. In addition, the effect of prophylactic treatment on gynecomastia remains uncertain. We aimed to evaluate the incidence of gynecomastia and breast pain in prostate cancer patients treated with ARPIs compared with androgen deprivation therapy (ADT) and the effect of prophylactic treatment for these AEs due to antiandrogen therapy. Methods: In June 2024, we queried four databases―PubMed, Scopus, Web of Science, and Embase―for randomized controlled trials (RCTs) investigating prostate cancer treatments involving antiandrogen therapy. The endpoints of interest were the incidence of these AEs due to ARPIs and the effect of prophylactic treatment for these. Key findings and limitations: Eighteen RCTs, comprising 5036 patients, were included in the systematic review and meta-analysis. ARPIs included enzalutamide, darolutamide, and apalutamide. The results indicated that patients who received ARPI monotherapy had a significantly higher incidence of gynecomastia than those who received ADT monotherapy (risk ratio [RR]: 5.19, 95% confidence interval [CI]: 3.58–7.51, p < 0.001). There was no significant difference in the incidence of gynecomastia between ARPI plus ADT therapy and ADT monotherapy (RR: 1.27, 95% CI: 0.84–1.93, p = 0.2). Prophylactic tamoxifen or radiotherapy reduced significantly the incidence of gynecomastia and breast pain caused by bicalutamide monotherapy. Conclusions and clinical implications: We found that ARPI monotherapy increases the incidence of these AEs significantly compared with ADT. In contrast, ARPI plus ADT therapy did not result in a higher incidence of AEs. The use of either tamoxifen or radiotherapy was effective in reducing the incidence of these AEs due to bicalutamide monotherapy. These prophylactic treatments could reduce the incidence of AEs due to ARPI monotherapy. However, further studies are needed to clarify their efficacy. Patient summary: Although androgen deprivation therapy (ADT) improves overall survival in patients with prostate cancer, it is associated with several complications. Androgen receptor pathway inhibitor (ARPI) monotherapy has emerged as a promising strategy for improving oncological outcomes in these patients. However, ARPI monotherapy increases gynecomastia and breast pain in prostate cancer patients compared with ADT, while ARPI plus ADT did not result in a higher incidence of adverse events. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2466 25 1 2025 Co-occurrence of interstitial lung disease and pulmonary embolism as adverse events of adjuvant osimertinib treatment for EGFR mutant non-small cell lung cancer: a case report 311 EN Kenta Manabe Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Shinichi Furukawa Department of Thoracic Surgery, Okayama University Hospital Tomoya Seno Department of Thoracic Surgery, Okayama University Hospital Kousei Ishimura Department of Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background Postoperative osimertinib for EGFR mutant non-small cell lung cancer has become the standard of care. However, its adverse events in clinical practice remain unclear. We report a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment. Case presentation A 74-year-old woman, diagnosed with left lower lobe lung adenocarcinoma harboring an EGFR mutation, underwent a left lower lobectomy with lymph node dissection. During adjuvant osimertinib therapy, the patient developed respiratory distress with hypoxia, leading to the diagnosis of interstitial lung disease. Despite immediate steroid therapy, respiratory distress persisted, the patient developed leg edema. She was diagnosed with deep vein thrombosis and pulmonary embolism via contrast-enhanced computed tomography scan. Following treatment with steroid and anticoagulation, her clinical symptoms improved rapidly, and she showed no recurrence of interstitial lung disease, pulmonary embolism, or lung cancer over the following nine months. Conclusions We encountered a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment. In patients with osimertinib-induced interstitial lung disease, particularly when respiratory symptoms show poor improvement with steroid treatment, the possibility of pulmonary embolism complications should be suspected. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 4 2025 Japanese translation of the Functional Assessment of Cancer Therapy-Breast + 4 (FACT-B + 4) following international guidelines: a verification of linguistic validity 773 782 EN Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Nozomu Takata Simpson Querrey Biomedical Research Center, Northwestern University Saya R. Dennis Department of Preventive Medicine Feinberg School of Medicine, Northwestern University Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Yasuaki Sagara Department of Breast Surgical Oncology, Social Medical Corporation Hakuaikai Sagara Hospital Takehiko Sakai Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital of JFCR Shin Takayama Department of Breast Surgery, National Cancer Center Hospital Dai Kitagawa Department of Breast Surgical Oncology, National Center for Global Health and Medicine Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Hospital Tomomi Fujisawa Department of Breast Cancer, Gunma Prefectural Cancer Center Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background For breast cancer patients, postoperative lymphedema and upper limb movement disorders are serious complications that absolutely reduce their quality of life (QOL). To evaluate this serious complication, we used “Quick Dash” or “FACT-B”, which can assess a patient's physical, social, emotional, and functional health status. To evaluate their breast cancer surgery-related dysfunction correctly, “FACT-B + 4” was created by adding four questions about “arm swelling'' and “tenderness”. We have translated it into Japanese according to international translation guidelines. Methods At the beginning, we contacted FACT headquarters that we would like to create a Japanese version of FACT-B + 4. They formed the FACIT Trans Team (FACIT) following international translation procedures, and then, we began translating according to them. The steps are 1: perform “Forward and Reverse translations” to create a “Preliminary Japanese version”, 2: request the cooperation of 5 breast cancer patients and “conduct a pilot study” and “questionnaire survey”, and 3: amendments and final approval based on pilot study results and clinical perspectives. Result In Step1, FACIT requested faithful translation of the words, verbs, and nouns from the original text. In Step2, patients reported that they felt uncomfortable with the Japanese version words such as “numb'' and “stiffness'' and felt that it might be difficult to describe their symptoms accurately. In Step3, we readjusted the translation to be more concise and closer to common Japanese language, and performed “Step1” again to ensure that the translation definitely retained the meaning of the original. Conclusion A Japanese version of FACT has existed until now, but there was no Japanese version of FACT-B + 4, which adds four additional items to evaluate swelling and pain in the upper limbs. This time, we have created a Japanese version that has been approved by FACT. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 1109-6535 22 4 2025 C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness 510 524 EN YUSUKE OTANI Department of Pathology, Beth Israel Deaconess Medical Center MASAKI MAEKAWA Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI TANAKA Department of Pathology, Beth Israel Deaconess Medical Center TIRSO PEÑA Department of Pathology, Beth Israel Deaconess Medical Center VANESSA D. CHIN UMass Chan Medical School, UMass Memorial Medical Center ANNA ROGACHEVSKAYA Department of Pathology, Beth Israel Deaconess Medical Center SHINICHI TOYOOKA Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MICHAEL H. ROEHRL Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI FUJIMURA Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma. Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA). Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma. Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50’s impact on melanoma progression and patient prognosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients e83484 EN Toshihiko Matsuo Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Atsushi Muraoka Department of Surgery, Kagawa Rosai Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project‑14 EN Shogo NAKAMOTO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Emotional Changes among Young Patients with Breast Cancer to Foster Relationship-Building with Their Partners: A Qualitative Study 185 195 EN Ayumi Yoshikawa Faculty of Nursing, Osaka Dental University Naruto Taira Kawasaki Medical School, Department of Breast and Thyroid Surgery Mayumi Okanaga Gifu College of Nursing, Nursing of Children and Child-Rearing Families Shinya Saito Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/68726 We investigated the emotional changes that young patients with breast cancer need to undergo in order to foster relationship-building with their partners by conducting a qualitative descriptive study (March 1 to Nov. 26, 2021) and semi-structured interviews with eight postoperative patients (age 20-40 years) with breast cancer. The data were analyzed using the modified grounded theory approach (M-GTA), yielding five categories: (i) Awareness of being a breast cancer patient, (ii) Being at a loss, (iii) Support from significant others, (iv) The struggle to transition from being a patient with cancer to becoming “the person I want to be”, and (v) Reaching the “me” I want to be who can face building a relationship with a partner. These findings suggest that young breast cancer patients must feel that they can lead a normal life through activities such as work or acquiring qualifications before building relationships with their partners, and that getting closer to their desired selves is important. Nurses can provide information to young patients with breast cancer to assist them in building a solid relationship with their partners. We believe that this support may enhance the patients’ quality of life and help them achieve stronger relationships with their partners. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0306-5251 91 9 2025 Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase 2659 2671 EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Tomonori Sakai Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data. Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR). Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38). Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0959-8049 220 2025 Genomic landscape and clinical impact of homologous recombination repair gene mutation in small bowel adenocarcinoma 115401 EN Toshiki Ozato Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shigeru Horiguchi Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichiro Tsutsumi Department of Gastroenterology, Okayama University Hospital Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Although homologous recombination deficiency has been studied as a biomarker for other cancer types, the clinical and genomic implications of homologous recombination repair (HRR) gene mutations in SBA remain unclear. Methods: We retrospectively analyzed the data of 628 patients with advanced or recurrent SBA from a nationwide genomic database. Patients were categorized into HRR mutation and non-HRR mutation groups and compared for their clinical and genomic characteristics including tumor mutational burden (TMB) and microsatellite instability-high (MSI-H) were compared. Treatment efficacy and overall survival (OS) were assessed based on HRR gene mutation status and primary tumor site (duodenal adenocarcinoma [DA] vs. small intestinal carcinoma [SIC]). Results: Patients with the HRR mutations had higher frequencies of TMB and MSI-H than those without the mutation (P < 0.0001). In DA, HRR gene mutation positivity was associated with improved OS and higher overall response rates (ORR) to platinum-based chemotherapy (OS: not reached vs. 23.5 months, P = 0.040; ORR: 33 % vs. 19 %, P = 0.046), whereas no significant associations were observed with SIC. Conclusion: HRR gene mutation may be a potential biomarker for platinum-based chemotherapy efficacy in SBA, especially in DA, highlighting the need for site-specific therapies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7634 14 8 2025 Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer e70793 EN Tomohiro Kamio Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Hirosuna Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Ozato Department of Gastroenterology, Okayama University Hospital Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes. Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro. Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations. Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Effectiveness of Postoperative Irradiation in Patients with cN0 Early Breast Cancer Treated with Sentinel Lymph Node Surgery 101 107 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Yuka Isozaki Department of Surgery, Oomoto Hospital Original Article /10.18926/AMO/68648 To evaluate the effectiveness of postoperative irradiation (POI) for patients with cN0 early breast cancer, we retrospectively analyzed the cases of 650 consecutive breast cancer patients who underwent sentinel lymph node (SLN)-guided surgery (2005-2022) at our hospital. In this cohort, 53% (278/521) of the patients who underwent breast conservative surgery (BCS) and 96% (124/129) of those treated with mastectomy did not receive POI. The patients who underwent BCS were treated with POI using opposing tangential field irradiation. A false negative (FN) SLN was retrospectively defined as a negative metastasis in SLN plus positive recurrence in the axillary lymph nodes. Recurrence was detected in 83 patients. A logistic regression analysis revealed that the nuclear grade (odds ratio [OR] 1.69), POI (OR 0.41), and postoperative hormone therapy (OR 0.40) were each significantly related to recurrence. The 26.1% (12/46) FN rate of the non-POI patients decreased to 5.8% (1/17) compared to those treated with POI. The rate of axillary recurrence was significantly lower in the POI group (0.4%) versus the non-POI group (2.7%) (p=0.0355). The rate of locoregional recurrence was also significantly lower in the POI group (2.0%) versus the non-POI group (13.4%) (p<0.0001). No significant difference was observed in the rate of distant recurrence between the POI (4.0%) and non-POI (3.3%) (p=0.831) groups. These results indicated that the postoperative opposing tangential field irradiation of conserved breast tissue inhibited recurrence in the axillary lymph nodes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1068 35 1 2025 Primary chest wall sarcoma: advances in surgical management and outcomes 141 EN Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Tsuyoshi Ryuko Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuto Itano Department of Orthopedic Surgery, Okayama University Hospital Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose Although rare, primary chest wall sarcomas are complex malignancies necessitating optimal local control and comprehensive treatment. This study aimed to review 9 years of cases of primary chest wall sarcomas at a single institution, focusing on their histology, surgical management, and prognosis. Methods A retrospective analysis was performed on 19 patients undergoing chest wall resection for sarcoma from 2012 to 2020. Data on demographics, tumor specifics, resection extent, and adjuvant therapies were collected. Surgical and postoperative outcomes were also assessed. Results The median patient age was 64 years. Chondrosarcoma was the most common histology. R0 resection was achieved in all patients, with early postoperative complications occurring in 11% of the patients. Robust chest wall reconstruction was performed, resulting in minimal respiratory complications. The 5-year overall survival and disease-free survival rates were 94% and 68%, respectively. Tumor size and patient age were significant prognostic factors for local recurrence. Conclusion Comprehensive surgical resection, coupled with multidisciplinary preoperative planning, achieves favorable outcomes. Patients aged ≥ 70 years and with tumor size ≥ 5 cm (P = .047) should be carefully followed up for local recurrence. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 15 6 2025 Robustness of Machine Learning Predictions for Determining Whether Deep Inspiration Breath-Hold Is Required in Breast Cancer Radiation Therapy 668 EN Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Jamal, Ghaida Al Jamal Department of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Deep inspiration breath-hold (DIBH) is a commonly used technique to reduce the mean heart dose (MHD), which is critical for minimizing late cardiac side effects in breast cancer patients undergoing radiation therapy (RT). Although previous studies have explored the potential of machine learning (ML) to predict which patients might benefit from DIBH, none have rigorously assessed ML model performance across various MHD thresholds and parameter settings. This study aims to evaluate the robustness of ML models in predicting the need for DIBH across different clinical scenarios. Methods: Using data from 207 breast cancer patients treated with RT, we developed and tested ML models at three MHD cut-off values (240, 270, and 300 cGy), considering variations in the number of independent variables (three vs. six) and folds in the cross-validation (three, four, and five). Robustness was defined as achieving high F2 scores and low instability in predictive performance. Results: Our findings indicate that the decision tree (DT) model demonstrated consistently high robustness at 240 and 270 cGy, while the random forest model performed optimally at 300 cGy. At 240 cGy, a threshold critical to minimize late cardiac risks, the DT model exhibited stable predictive power, reducing the risk of overestimating DIBH necessity. Conclusions: These results suggest that the DT model, particularly at lower MHD thresholds, may be the most reliable for clinical applications. By providing a tool for targeted DIBH implementation, this model has the potential to enhance patient-specific treatment planning and improve clinical outcomes in RT. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 0008-5472 85 6 2025 Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy 1082 1096 EN Toshifumi Ninomiya Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Kemmotsu Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ai Miyamoto Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kota Tachibana Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Joji Ishida Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Otani Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Tanaka Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Isamu Okamoto Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases. Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1863-6705 2025 Novel pulmonary abdominal normothermic regional perfusion circuit for simultaneous in-donor evaluation and preservation of lungs and abdominal organs in donation after circulatory death EN Shin Tanaka Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Umeda Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroyuki Ujike Department of General Thoracic Surgery, Shimane University Graduate School of Medicine Tsuyoshi Ryuko Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuaki Tomioka Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kentaroh Miyoshi Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mikio Okazaki Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Seiichiro Sugimoto Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Objective To overcome limitations of traditional ex vivo lung perfusion (EVLP) for controlled donation after circulatory death (cDCD) lungs, this study aimed to evaluate a novel pulmonary abdominal normothermic regional perfusion (PANRP) technique, which we uniquely designed, for in situ assessment of lungs from cDCD donors. Methods We modified the abdominal normothermic regional perfusion circuit for simultaneous lung and abdominal organ assessment using independent extracorporeal membrane oxygenation components. Blood was oxygenated via a membrane oxygenator and returned to the body, with pulmonary flow adjusted to maintain pressure < 25 mmHg. Femoral cannulation was performed, and the lungs were ventilated with standard settings. Organ function was assessed over 2 h using PaO2/FiO2, AST, ALT, BUN, and Cr measurements to monitor perfusion and oxygen delivery. Results PANRP maintained stable lung function, with P/F ratios above 300, and preserved abdominal organ parameters, including stable AST, ALT, BUN, and Cr levels. Adequate urine output was observed, indicating normal renal function. Pulmonary artery pressure remained < 20 mmHg, and pulmonary vascular resistance was kept at 400 dyn・s/cm5, showing no signs of lung dysfunction or injury throughout the circuit. Conclusions PANRP offers a promising alternative to traditional EVLP for cDCD lung evaluation, allowing in situ assessment of multiple organs simultaneously. This approach may overcome logistical and economic challenges associated with ex vivo techniques, enabling a more efficient evaluation process. Further studies are warranted to confirm its clinical applicability and impact on long-term outcomes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0939-6411 209 2025 Repeated sequential administration of pegylated emulsion of SU5416 and liposomal paclitaxel enhances anti-tumor effect in 4T1 breast cancer-bearing mice 114663 EN Masato Maruyama Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University Reiya Torii Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University Hazuki Matsui Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University Hiroki Hayashi Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University Ken-ichi Ogawara Laboratory of Pharmaceutics, Kobe Pharmaceutical University Kazutaka Higaki Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University To improve vascular normalization strategy for intractable triple-negative breast cancer 4T1, we examined the anti-tumor effects of repeated sequential administration of polyethylene glycol (PEG)-modified emulsion of SU5416 (PE-SU5416), a vascular endothelial growth factor (VEGF) receptor-2 kinase inhibitor, and PEG-modified liposomal paclitaxel (PL-PTX) in mice bearing 4T1 cells. Three sequential administrations (Seq×3) of PE-SU5416 and PL-PTX exhibited significantly higher anti-tumor activity than a single sequential administration (Seq×1). The tumor vasculatures were structurally normalized until after two PE-SU5416 (PE-SU5416×2) or sequential (Seq×2) administrations, while the improvement in vascular function, such as oxygen supply, blood flow, and PEG-liposomal distribution, was evident until after three administrations of PE-SU5416 (PE-SU5416×3) and Seq×3. Although some discrepancies between the structural and functional improvement in tumor vasculatures were observed after PE-SU5416×3 and Seq×3, cancer-associated fibroblasts (CAFs) and collagen levels were significantly reduced after PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3, suggesting that a possible decrease in interstitial fluid pressure due to the reduction in CAFs and collagen would have compensated for vascular function. Furthermore, PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3 significantly decreased tumor growth factor-β (TGF-β), an activator of CAFs, in tumor tissues, suggesting that the reduction in TGF-β levels by PE-SU5416 suppresses CAF activation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Photoinitiators Induce Histamine Production in Human Mast Cells 51 58 EN Taro Miura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Kawasaki Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University Hirofumi Hamano Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article /10.18926/AMO/68362 Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Gastrectomy Causes an Imbalance in the Trunk Muscles 9 19 EN Nanami Ikeya Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Okita Department of Surgery, Okayama City Hospital Shinsuke Hashida Department of Surgery, Okayama City Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Hirokuni Ikeda Department of Surgery, Okayama City Hospital Kazunori Tsukuda Department of Surgery, Okayama City Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article /10.18926/AMO/68354 Muscle loss negatively affects gastrectomy prognosis. However, muscle loss is recognized as a systemic change, and individual muscle function is often overlooked. We investigated changes in the muscle volume of individual muscles after gastrectomy to identify clues for prognostic factors and optimal rehabilitation programs. Patients who underwent R0 gastrectomy for Stage I gastric cancer at our hospital from 2015 to 2021 were retrospectively selected to minimize the effects of malignancy and chemotherapy. Trunk muscle volume was measured by computed tomography to analyze body composition changes. Statistical analysis was performed to identify risk factors related to body composition changes. We compared the preoperative and 6-month postoperative conditions of 59 patients after gastrectomy. There was no difference in the psoas major muscle, a conventional surrogate marker of sarcopenia. There were significant decreases in the erector spinae (p=0.01) and lateral abdominal (p=0.01) muscles, and a significant increase in the rectus abdominis muscle (p=0.02). No significant correlation was found between these muscle changes and nutritional status. Body composition imbalance may serve as a new indicator of the general condition of patients after gastrectomy. Rehabilitation to correct this imbalance may improve prognosis after gastrectomy. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 121 35 2024 Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity e2320189121 EN Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuma Iwata Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Inozume Department of Dermatology, Chiba University Graduate School of Medicine Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Toshihide Ueno Division of Cellular Signaling, National Cancer Center Research Institute Hideki Ikeda Division of Cell Therapy, Chiba Cancer Research Institute Katsushige Kawase Division of Cell Therapy, Chiba Cancer Research Institute Yuka Saeki Department of Dermatology, Chiba University Graduate School of Medicine Shusuke Kawashima Department of Dermatology, Chiba University Graduate School of Medicine Kazuo Yamashita KOTAI Biotechnologies, Inc. Yu Kawahara Department of Dermatology, Chiba University Graduate School of Medicine Yasuhiro Nakamura Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Hiroko Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Dansako Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuyoshi Kawamura Department of Dermatology, University of Yamanashi Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa Hiroaki Honda Department of Pathology, Tokyo Women's Medical University Hiroyuki Mano Division of Cellular Signaling, National Cancer Center Research Institute Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Masahito Kawazu Division of Cell Therapy, Chiba Cancer Research Institute Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 1 2025 Trends in uptake of cancer screening among people with severe mental illness before and after the COVID-19 pandemic in Japan: A repeated cross-sectional study e70062 EN Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Kiwamu Nagoshi Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Aim: The aim of this study was to investigate trends in cancer screening participation among people with severe mental illness (PSMI) from periods before and after the COVID-19 pandemic. Methods: In this repeated cross-sectional study, we used anonymized datasets on municipal cancer screening participation among PSMI in Okayama City. The data covered fiscal year (FY) 2018 to FY2022; we used the municipal cancer screening database and Medical Payment for Services and Supports for Persons with Disabilities. PSMI were defined as those with schizophrenia or related psychotic disorders (F20-29) or bipolar disorder (F30 or F31), identified using International Classification of Diseases, Tenth Revision, codes. The analysis included men and women aged 40-69 years for colorectal and lung cancer screening; men and women aged 50-69 years for gastric cancer screening; women aged 40-69 years for breast cancer screening; and women aged 20-69 years for cervical cancer screening. Municipal cancer screening rates among PSMI were calculated for each FY. Results: For all cancer types, cancer screening rates for PSMI in FY2020 (colorectal: 9.0%; lung: 11.6%; gastric: 4.9%; breast: 6.2%; and cervical: 6.1%) were lower than the rates in FY2019 (11.5%, 14.0%, 6.5%, 9.3%, and 8.3%, respectively). In FY2022, the rates (9.9%, 12.9%; 5.3%; 8.0%, and 6.9%, respectively) recovered, but remained low. Conclusion: This study showed that cancer screening rates among PSMI were very low, both before and after the COVID-19 pandemic. Efforts to encourage participation in cancer screening in this population are urgently needed. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer 2577 EN Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiichiro Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Kammei Rai Department of Allergy and Respiratory Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Katsuyuki Hotta Department of Allergy and Respiratory Medicine, Okayama University Hospital Masahiro Tabata Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0–1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p = 0.009; median OS: 15.4 vs. 38.0 months, p = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1053-2498 44 2 2024 Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor 249 260 EN Shinichi Kawana Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohisa Sakaue Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Kohei Hashimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Nakata Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine Haruki Choshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Ohtani Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD. Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1－/－) mice. Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1－/－ donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1－/－ donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1－/－ recipient. Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Case of Radiation-Induced Angiosarcoma after Breast-Conserving Surgery with Hypofractionated Radiotherapy in a Japanese Patient 453 458 EN Yujiro Kawata Department of Radiology, Kawasaki Medical School Kenta Watanabe Department of Radiology, Kawasaki Medical School Ryoji Tokiya Department of Radiology, Kawasaki Medical School Takeshi Matsuno Department of Pathology, Kawasaki Medical School Ryo Tanaka Department of Dermatology, Kawasaki Medical School Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Kuniaki Katsui Department of Radiology, Kawasaki Medical School Case Report 10.18926/AMO/67871 Radiation-induced angiosarcoma (RIAS) is a rare, late adverse event of radiotherapy comprising approximately half of all radiation-induced sarcomas. It has a relatively short latency period and generally unfavorable prognosis. This study presents a case of RIAS that developed 5 years and 11 months after the completion of hypofractionated radiotherapy (42.56 Gy/16 fractions) following partial mastectomy. The patient was diagnosed with RIAS 10 months after the onset of skin redness. She underwent skin tumor resection, followed by paclitaxel, then pazopanib administration, but no radiotherapy. At 6 years and 2 months after surgery, no RIAS recurrence has been detected. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 2 2024 The role of C1orf50 in breast cancer progression and prognosis 292 305 EN Yusuke Otani Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School Atsushi Tanaka Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School Masaki Maekawa Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School Tirso Peña Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School Anna Rogachevskaya Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School Teruhiko Ando Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuto Itano Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruyoshi Katayama Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyoshi Doihara Department of General Surgery, Kawasaki Medical School General Medical Center Michael H. Roehrl Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50’s involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2054-345X 11 1 2024 Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study 42 EN Mashu Futagawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Okazaki Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Hospital Chika Fukano Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Risa Osumi Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Fumino Kato Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Yusaku Urakawa Department of Genetic Medicine, School of Medicine, Fujita Health University Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The Specific Shapes of Capillaries are Associated with Worse Prognosis in Patients with Invasive Breast Cancer EN HNIN WINT WINT SWE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface EN Tetta TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis EN FAN JIANG Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1173-8804 39 1 2024 Real-World Comparative Analysis of Trastuzumab Originator and Biosimilars: Safety, Efficacy, and Cost Effectiveness 131 142 EN Tomoka Mamori Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Maki Tanioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenji Takada Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuguo Iwatani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background Despite the global use of trastuzumab biosimilars, concerns remain regarding their efficacy and safety. In particular, when used concurrently with pertuzumab, trastuzumab biosimilars lack extensive real-world data and safety information. Additionally, as cancer drug expenditures continue to rise worldwide, cost savings from biosimilars have become increasingly important. Objective This study aims to assess the safety, efficacy, and cost effectiveness of trastuzumab originators and their biosimilars in real-world clinical settings, focusing on a large patient population. Methods The analysis included 31,661 patients with HER2-positive breast cancer from the Medical Data Vision Co., Ltd. database in Japan. Additionally, adverse event reports for the trastuzumab originator and its biosimilars were obtained for 58,799 patients from the World Health Organization’s VigiBase, the global adverse event reporting database. Results No significant differences were observed in heart failure hospitalizations, liver dysfunction, or infusion reaction rates in both the Medical Data Vision Co., Ltd. database and the World Health Organization’s VigiBase. In the Medical Data Vision Co., Ltd. database, the addition of pertuzumab did not significantly influence the incidence of adverse events, and the use of biosimilars significantly reduced medical costs, with no significant difference in breast cancer recurrence rates. Conclusions By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-0333 18 1 2024 Deep learning-based approach for acquisition time reduction in ventilation SPECT in patients after lung transplantation 47 57 EN Masahiro Nakashima Division of Radiological Technology, Okayama University Hospital Ryohei Fukui Department of Radiological Technology, Faculty of Health Sciences, Okayama University Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University We aimed to evaluate the image quality and diagnostic performance of chronic lung allograft dysfunction (CLAD) with lung ventilation single-photon emission computed tomography (SPECT) images acquired briefly using a convolutional neural network (CNN) in patients after lung transplantation and to explore the feasibility of short acquisition times. We retrospectively identified 93 consecutive lung-transplant recipients who underwent ventilation SPECT/computed tomography (CT). We employed a CNN to distinguish the images acquired in full time from those acquired in a short time. The image quality was evaluated using the structural similarity index (SSIM) loss and normalized mean square error (NMSE). The correlation between functional volume/morphological volume (F/M) ratios of full-time SPECT images and predicted SPECT images was evaluated. Differences in the F/M ratio were evaluated using Bland–Altman plots, and the diagnostic performance was compared using the area under the curve (AUC). The learning curve, obtained using MSE, converged within 100 epochs. The NMSE was significantly lower (P < 0.001) and the SSIM was significantly higher (P < 0.001) for the CNN-predicted SPECT images compared to the short-time SPECT images. The F/M ratio of full-time SPECT images and predicted SPECT images showed a significant correlation (r = 0.955, P < 0.0001). The Bland–Altman plot revealed a bias of -7.90% in the F/M ratio. The AUC values were 0.942 for full-time SPECT images, 0.934 for predicted SPECT images and 0.872 for short-time SPECT images. Our findings suggest that a deep-learning-based approach can significantly curtail the acquisition time of ventilation SPECT, while preserving the image quality and diagnostic accuracy for CLAD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 The First Report of Bickerstaff Brainstem Encephalitis Induced by Atezolizumab for Metastatic Breast Cancer 407 412 EN Kyoko Shimoyama Department of Breast Surgery, Takatsuki General Hospital Atsushi Nakajima Department of Rehabilitation, Aijinkai Rehabilitation Hospital Yoshimitsu Minari Department of Breast Surgery, Takatsuki General Hospital Case Report 10.18926/AMO/67665 Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they have been known to cause immune-related adverse events (irAEs) by promoting T-cell activation. Neurological irAEs are rare (1%) but have a high fatality rate (11.5%). Here we report the first case of Bickerstaff brainstem encephalitis (BBE) induced by an ICI. A woman in her 60s with metastatic breast cancer was treated with atezolizumab plus nab-paclitaxel once intravenously. Eighteen days later, she lost consciousness with ophthalmoplegia and was diagnosed with a neurological irAE. She recovered consciousness immediately with the administration of intravenous immunoglobulin (IVIG) but suffered severe permanent peripheral neuropathy. Although it is just one case, this experience shows that BBE occurring as a neurological irAE of ICI cancer treatment may be associated with more severe outcomes than conventional BBE in metastatic cancer. Creating a system for multidisciplinary treatment is essential for ICI therapy. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 2473-4284 8 2024 Response to Imatinib in a Patient With Gastric Adenocarcinoma With KIT Q556_K558 In-Frame Deletion: A Case Report e2400228 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Kunio Okamoto Department of Medical Oncology, Kagawa Prefectural Central Hospital Midori Ando Department of Pathology, Kagawa Prefectural Central Hospital, Satoko Nakamura Department of Pathology, Kagawa Prefectural Central Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Yoshiyuki Ayada Department of Pathology, Okayama University Hospital Go Makimoto Center for Clinical Oncology, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Natsuko Okita Research Management Division, Clinical Research Support Office, National Cancer Center Hospital Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 136 2 2024 令和５年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 54 56 EN Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 15 2024 Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients 8370 EN Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kou Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Goro Kimura Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Haruto Yamada Department of Infectious Disease, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrine Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 2633-0679 5 9 2024 Novel strategy for activating gene expression through triplex DNA formation targeting epigenetically suppressed genes 884 890 EN Ryotaro Notomi Graduate School of Pharmaceutical Sciences, Kyushu University Shigeki Sasaki Graduate School of Pharmaceutical Sciences, Nagasaki International University Yosuke Taniguchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Triplex DNA formation is a useful genomic targeting tool that is expected to have a wide range of applications, including the antigene method; however, there are fundamental limitations in its forming sequence. We recently extended the triplex DNA-forming sequence to methylated DNA sequences containing 5mCG base pairs by developing guanidino-dN, which is capable of recognizing a 5mCG base pair with high affinity. We herein investigated the effect of triplex DNA formation using TFOs with guanidino-dN on methylated DNA sequences at the promoter of the RASSF1A gene, whose expression is epigenetically suppressed by DNA methylation in MCF-7 cells, on gene expression. Interestingly, triplex DNA formation increased the expression of the RASSF1A gene at the transcript and protein levels. Furthermore, RASSF1A-activated MCF-7 cells exhibited cell growth suppressing activity. Changes in the expression of various genes associated with the promotion of apoptosis and breast cancer survival accompanied the activation of RASSF1A in cells exhibited antiproliferative activity. These results suggest the potential of increases in gene expression through triplex DNA formation as a new genomic targeting tool. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-5345 62 5 2024 Augmented humoral response to third and fourth dose of SARS-CoV-2 mRNA vaccines in lung transplant recipients 804 810 EN Shinichi Kawana Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Choshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Ishihara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Hashimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs. Methods: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses. Results: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021). Conclusion: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6806 208 2024 Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306 145- 154 EN Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Keita Sasaki JCOG Data Center/Operations Office, National Cancer Center Hospital Junki Mizusawa JCOG Data Center/Operations Office, National Cancer Center Hospital Futoshi Akiyama Department of Pathology, Cancer Institute Hospital Masafumi Kurosumi Department of Diagnostic Pathology, Kameda Kyobashi Clinic Masataka Sawaki Department of Breast Oncology, Aichi Cancer Center Hospital Nobuko Tamura Department of Breast Surgery, Toranomon Hospital Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Takahiro Kogawa Department of Breast Medical Oncology, Cancer Institute Hospital Mina Takahashi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Naoki Hayashi Department of Breast Surgery Oncology, St Lukes International Hospital Hirofumi Mukai Department of Breast and Medical Oncology, National Cancer Center Hospital East Norikazu Masuda Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital Fumikata Hara Department of Breast Medical Oncology, Cancer Institute Hospital Hiroji Iwata Department of Breast Oncology, Aichi Cancer Center Hospital Background In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. Methods We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. Results ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175–0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073–0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. Conclusions RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 5 2024 PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer e0300644 EN Yin Min Thu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Kosuke Ochi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shimpei Tsudaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumiaki Takatsu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichi Date Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoki Matsuda Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuma Iwata Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Nakata Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2234-943X 14 2024 Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis 1371307 EN Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ni Luh Gede Yoni Komalasari Faculty of Medicine, Udayana University Carlos Ichiro Kasano-Camones Faculty of Science and Technology, Division of Molecular Science, Gunma University Kazumi Ninomiya Faculty of Science and Technology, Division of Molecular Science, Gunma University Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Gohara Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Ochi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences I. Made Winarsa Ruma Faculty of Medicine, Udayana University I. Wayan Sumardika Faculty of Medicine, Udayana University Jin Zhou Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology Tomoko Honjo Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshihiko Sakaguchi Department of Microbiology, Tokushima Bunri University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eisaku Kondo Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-beta 1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-beta 1 hastens the invasive outgrowth of TNBC cells at the molecular level. Methods LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively. Results Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-kappa B (NF-kappa B). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-beta activated kinase 1 (TAK1) were required for the activation of NF-kappa B through I kappa beta kinase kinase (IKK alpha/beta) phosphorylation. Conclusion Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-beta 1-TRAF4-TAK1-IKK alpha/beta-I kappa beta alpha-NF-kappa B-MMP9, is crucial for TNBC cell invasiveness. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer 9869 EN Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Shinichiro Kubo Department of Breast and Thyroid Surgery, Fukuyama City Hospital Mari Yamamoto Department of Breast and Thyroid Surgery, Fukuyama City Hospital Tetsumasa Yamashita Department of Breast and Thyroid Surgery, Fukuyama City Hospital Chihiro Kuwahara Department of Breast and Thyroid Surgery, Fukuyama City Hospital Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/mu L for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma 285 290 EN Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report /10.18926/AMO/67204 Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1320-5463 74 7 2024 The specific shapes of capillaries are associated with worse prognosis in patients with invasive breast cancer 394 407 EN Hnin‐Wint‐Wint Swe Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Komatsubara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) is associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined based on the MVD value, and the presence of GMP and other blood vessels with other specific shapes. As a result, high MVD value and the presence of GMP were not associated with worse prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index. Thus, the morphology of capillaries rather than MVD can be a better indicator of tumor aggressiveness. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Development and validation of a symptom illustration scale from the patient-reported outcome common terminology criteria for adverse events for patients with breast cancer EN Yoko SUZUKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-1291 54 11 2024 Effective division of the intersegmental plane using a robotic stapler in robotic pulmonary segmentectomy 1319 1328 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Hashimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purposes Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes. Methods RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period. Results The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS. Conclusions The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 115 7 2024 Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer 2333 2345 EN Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruyoshi Katayama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yidan Zhu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rongsheng Huang Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University Takafumi Shigehira Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6806 202 3 2023 Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer 473 483 EN Shinsuke Sasada Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Naoto Kondo Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences Hiroya Hashimoto Core Laboratory, Nagoya City University Graduate School of Medical Sciences Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Kumiko Kida Department of Breast Surgical Oncology, St. Luke’s International Hospital Yasuaki Sagara Department of Breast and Thyroid Surgical Oncology, Social medical corporation Hakuaikai, Sagara Hospital Takayuki Ueno Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Keisei Anan Department of Surgery, Kitakyushu Municipal Medical Center Akihiko Suto Department of Breast Surgery, National Cancer Center Hospital Chizuko Kanbayashi Department of Breast Oncology, Niigata Cancer Center Hospital Mina Takahashi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Rikiya Nakamura Department of Breast Surgery, Chiba Cancer Center Toshiyuki Ishiba Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Michiko Tsuneizumi Department of Breast Surgery, Shizuoka General Hospital Seiichiro Nishimura Department of Breast Surgery, Shizuoka Cancer Center Hospital Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Fumikata Hara Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroji Iwata Department of Breast Oncology, Aichi Cancer Center Hospital Purpose Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. Methods We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. Results Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). Conclusions The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 30 11 2023 EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery 6697 6702 EN Toshiya Fujiwara Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiko Shien Okayama University Thoracic Surgery Study Group (OUTSSG) Motoki Matsuura Okayama University Thoracic Surgery Study Group (OUTSSG) Junichi Soh Okayama University Thoracic Surgery Study Group (OUTSSG) Hiromasa Yamamoto Okayama University Thoracic Surgery Study Group (OUTSSG) Soshi Takao Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuho Maki Okayama University Thoracic Surgery Study Group (OUTSSG) Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group (OUTSSG) Ryujiro Sugimoto Okayama University Thoracic Surgery Study Group (OUTSSG) Ken Suzawa Okayama University Thoracic Surgery Study Group (OUTSSG) Mikio Okazaki Okayama University Thoracic Surgery Study Group (OUTSSG) Hiroyuki Tao Okayama University Thoracic Surgery Study Group (OUTSSG) Makio Hayama Okayama University Thoracic Surgery Study Group (OUTSSG) Masafumi Kataoka Okayama University Thoracic Surgery Study Group (OUTSSG) Yoshifumi Sano Okayama University Thoracic Surgery Study Group (OUTSSG) Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group (OUTSSG) Motohiro Yamashita Okayama University Thoracic Surgery Study Group (OUTSSG) Osamu Kawamata Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiko Kataoka Okayama University Thoracic Surgery Study Group (OUTSSG) Shinichi Toyooka Okayama University Thoracic Surgery Study Group (OUTSSG) Background. Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. Patients and Methods. We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. Results. Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). Conclusion. Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0946-2716 101 4 2023 Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells 431 447 EN Yuma Gohara Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nahoko Tomonobu Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Rie Kinoshita Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Léna Audebert Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Youyi Chen Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ni Luh Gede Yoni Komalasari Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Fan Jiang Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Chikako Yoshizawa Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Murata Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ken-ichi Yamamoto Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masami Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiromi Kumon Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3―namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 28 7 2023 Trends and issues in clinical research on satisfaction and quality of life after mastectomy and breast reconstruction: a 5-year scoping review 847 859 EN Miho Saiga Department of Plastic Surgery, Okayama University Hospital Ryoko Nakagiri Department of Plastic Surgery, Okayama University Hospital Yuko Mukai Department of Plastic Surgery, Okayama Rosai Hospital Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Breast reconstruction (BR) aims to improve the satisfaction and quality of life (QOL) of breast cancer survivors. Clinical studies using patient-reported outcomes (PROs) can therefore provide relevant information to the patients and support decision-making. This scoping review was conducted to analyze recent trends in world regions, methods used, and factors investigated. The literature search was conducted in August 2022. Databases of PubMed, MEDLINE, and CINAHL were searched for relevant English-language studies published from 2017 to 2022. Studies involving women with breast cancer who underwent BR after mastectomy and investigated PROs after BR using BR-specific scales were included. Data on the country, publication year, study design, PRO measures (PROMs) used, time points of surveys, and research themes were collected. In total, 147 articles met the inclusion criteria. BREAST-Q was the most widely used, contributing to the increase in the number and diversification of studies in this area. Such research has been conducted mainly in North America and Europe and is still developing in Asia and other regions. The research themes involved a wide range of clinical and patient factors in addition to surgery, which could be influenced by research methods, time since surgery, and even cultural differences. Recent BR-specific PROMs have led to a worldwide development of research on factors that affect satisfaction and QOL after BR. PRO after BR may be influenced by local cultural and social features, and it would be necessary to accumulate data in each region to draw clinically useful conclusion. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1873-734X 63 3 2023 Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy ezad048 EN Mikio Okazaki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Shien Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromasa Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Araki Okayama University Thoracic Surgery Study Group (OUTSSG) Mototsugu Watanabe Okayama University Thoracic Surgery Study Group (OUTSSG) Masanori Okada Okayama University Thoracic Surgery Study Group (OUTSSG) Yuho Maki Okayama University Thoracic Surgery Study Group (OUTSSG) Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group (OUTSSG) Shinji Otani Okayama University Thoracic Surgery Study Group (OUTSSG) Ryujiro Sugimoto Okayama University Thoracic Surgery Study Group (OUTSSG) Hitoshi Nishikawa Okayama University Thoracic Surgery Study Group (OUTSSG) Riki Okita Okayama University Thoracic Surgery Study Group (OUTSSG) Makio Hayama Okayama University Thoracic Surgery Study Group (OUTSSG) Hiroyuki Tao Okayama University Thoracic Surgery Study Group (OUTSSG) Toshiya Fujiwara Okayama University Thoracic Surgery Study Group (OUTSSG) Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group (OUTSSG) Yuji Hirami Okayama University Thoracic Surgery Study Group (OUTSSG) Yoshifumi Sano Okayama University Thoracic Surgery Study Group (OUTSSG) Motohiro Yamashita Okayama University Thoracic Surgery Study Group (OUTSSG) Osamu Kawamata Okayama University Thoracic Surgery Study Group (OUTSSG) Motoki Matsuura Okayama University Thoracic Surgery Study Group (OUTSSG) Shinichi Toyooka Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy. RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy. No potential conflict of interest relevant to this article was reported.

Lippincott, Williams & Wilkins Acta Medica Okayama 2373-8731 10 5 2024 Postoperative Complications in Living Donors for Lung Transplantation e1617 EN Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Fujii Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Ishihara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Haruki Choshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Hashimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuji Okahara Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background. Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. Methods. The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022). Results. The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. Conclusions. Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2234-943X 14 2024 Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface 1371342 EN Tetta Takahashi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ni Luh Gede Yoni Komalasari Faculty of Medicine, Udayana University Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Gohara Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Ochi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences I. Made Winarsa Ruma Faculty of Medicine, Udayana University I. Wayan Sumardika Faculty of Medicine, Udayana University Jin Zhou Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology Tomoko Honjo Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshihiko Sakaguchi Department of Microbiology, Tokushima Bunri University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Eisaku Kondo Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Pharmacy, Okayama University Hospital Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-β1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain. Methods: Cell invasion was assessed using a transwell-based assay, protein–protein interactions by an immunoprecipitation–Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography. Results: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion. Conclusion: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-5345 62 2 2024 Long-term outcomes of lung transplantation requiring renal replacement therapy: A single-center experience 240 246 EN Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshio Shiotani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Choshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Ishihara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Life-long immunosuppressive therapy after lung transplantation (LT) may lead to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT). We aimed to investigate the characteristics and long-term outcomes of patients undergoing LT and requiring RRT. Methods This study was a single-center, retrospective cohort study. The patients were divided into the RRT (n = 15) and non-RRT (n = 170) groups. We summarized the clinical features of patients in the RRT group and compared patient characteristics, overall survival, and chronic lung allograft dysfunction (CLAD)-free survival between the two groups. Results The cumulative incidences of ESRD requiring RRT after LT at 5, 10, and 15 years were 0.8 %, 7.6 %, and 25.2 %, respectively. In the RRT group, all 15 patients underwent hemodialysis but not peritoneal dialysis, and two patients underwent living-donor kidney transplantation. The median follow-up period was longer in the RRT group than in the non-RRT group (P < 0.001). The CLAD-free survival and overall survival did not differ between the two groups. The 5-year survival rate even after the initiation of hemodialysis was 53.3 %, and the leading cause of death in the RRT group was infection. Conclusions Favorable long-term outcomes can be achieved by RRT for ESRD after LT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Ectopic Breast Cancer Arising within an Axillary Lymph Node 89 93 EN Kei Toshima Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Midori Filiz Nishimura Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Case Report 10.18926/AMO/66676 We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06) 15 20 EN Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Mina Takahashi Department of Breast Oncology, NHO Shikoku Cancer Center Kengo Kawada Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Shinichiro Kubo Department of Breast and Thyroid Surgery, Fukuyama City Hospital Daisuke Takabatake Department of Breast Surgery, Kochi Health Sciences Center Shoichiro Ohtani Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Kinya Matsuoka Department of Breast and Thyroid Surgery, Ehime Prefectural Central Hospital Hajime Hikino Department of Breast Surgery, Matsue Red Cross Hospital Yutaka Ogasawara Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Shozo Osumi Department of Breast Oncology, NHO Shikoku Cancer Center Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/66666 While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 115 3 2024 Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors 871 882 EN Haruyoshi Katayama Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Rongsheng Huang Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuto Itano Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2210-7703 46 2 2024 A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases 536 541 EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Shiho Sugimoto Department of Personalized Medicine and Preventive Healthcare Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Akihiko Nakamoto Department of Pharmacy, Okayama University Hospital Aya Fukuma Ozaki Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Background Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear. Aim We analysed two real-world databases, the World Health Organization’s VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib. Method Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis. Results Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group. Conclusion This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-4975 117 1 2024 Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer 181 188 EN Fumiaki Takatsu Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Mototsugu Watanabe Okayama University Thoracic Surgery Study Group Makio Hayama Okayama University Thoracic Surgery Study Group Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group Ryujiro Sugimoto Okayama University Thoracic Surgery Study Group Yuho Maki Okayama University Thoracic Surgery Study Group Toshiya Fujiwara Okayama University Thoracic Surgery Study Group Riki Okita Okayama University Thoracic Surgery Study Group Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group Hiroyuki Tao Okayama University Thoracic Surgery Study Group Yuji Hirami Okayama University Thoracic Surgery Study Group Eisuke Matsuda Okayama University Thoracic Surgery Study Group Kazuhiko Kataoka Okayama University Thoracic Surgery Study Group Motohiro Yamashita Okayama University Thoracic Surgery Study Group Yoshifumi Sano Okayama University Thoracic Surgery Study Group Motoki Matsuura Okayama University Thoracic Surgery Study Group Hisao Mizutani Okayama University Thoracic Surgery Study Group Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC. Methods A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer. Results At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival. Conclusions Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1880-7046 45 1 2023 Current status and challenges of breast cancer prevention∼DNA methylation would lead to groundbreaking progress in breast cancer prevention∼ 35 EN Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seema A. Khan Department of Surgery, Feinberg School of Medicine of Northwestern University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences The number of breast cancer patients is increasing worldwide. Furthermore, breast cancer often develops in young people, even those only in their 30s, who play a central role in their families and society. Results from many cohort studies suggest that dietary factors, alcohol consumption, lack of physical activity, obesity, nulliparity, breastfeeding, oral contraceptive use, fertility treatment and hormone replacement therapy are risk factors for breast cancer. However, the effects of lifestyle habits on the human body are complexly intertwined with various factors, and the effects vary from person to person depending on their constitution, etc., so there is no basis for this. Therefore, primary prevention of breast cancer is still not being implemented appropriately and efficiently. Furthermore, advances in genomic technology make it possible to assess the risk of developing breast cancer in some individuals. As a result, the establishment of breast cancer prevention methods has become a health priority for high-risk individuals. Drugs such as tamoxifen and raloxifene are known to prevent the development of breast cancer, based on the results of multiple randomized controlled trials, but there are concerns regarding the side effects of these powerful agents. In addition, several clinical studies have shown that prophylactic mastectomy for women who have BRCA mutations or who are identified as being at high risk reduces the incidence of breast cancer development. However, many issues, such as changes in long-term quality of life after preventive surgery, the optimal timing of surgery and the identification of women who are at high risk but will not develop breast cancer, remain uncertain. In other words, although many researchers have focused on chemoprevention and surgical prevention and clear preventive effects of these strategies have been confirmed, it cannot be said that they are widely accepted. Therefore, the current evidence for chemoprevention and surgical prevention, as well as highlights of several interesting lines of research currently underway, are summarized in this article. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0902-0063 38 1 2023 Impact of changes in skeletal muscle mass and quality during the waiting time on outcomes of lung transplantation e15169 EN Akikazu Hagiyama Division of Physical Medicine and Rehabilitation, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshimi Katayama Division of Physical Medicine and Rehabilitation, Okayama University Hospital Masanori Hamada Division of Physical Medicine and Rehabilitation, Okayama University Hospital Masuo Senda Division of Physical Medicine and Rehabilitation, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction: The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. We aimed to examine the association of changes in skeletal muscle mass and quality during the waiting time, as well as preoperative skeletal muscle mass and quality, with outcomes of LT. Methods: This study included individuals who underwent LT from brain-dead donors. Skeletal muscle mass (cm2/m2) and quality (mean Hounsfield units [HU]) of the erector spinae muscle at the 12th thoracic level were evaluated using computed tomography. Preoperative skeletal muscle mass and quality, and their changes during the waiting time were calculated. We evaluated the associations among mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, 6-minute walk distance at discharge, and 5-year survival after LT. Results: This study included 98 patients. The median waiting time was 594.5 days (interquartile range [IQR], 355.0–913.0). The median changes in skeletal muscle mass and quality were －4.4% (IQR, －13.3–3.1) and －2.9% (IQR, －16.0–4.1), respectively. Severe low skeletal muscle mass at LT was associated with prolonged ICU LOS (B = 8.46, 95% confidence interval [CI]: .51–16.42) and hospital LOS (B = 36.00, 95% CI: 3.23–68.78). Pronounced decrease in skeletal muscle mass during the waiting time was associated with prolonged MV duration (B = 7.85, 95% CI: .89–14.81) and ICU LOS (B = 7.97, 95% CI: .83–15.10). Conclusion: Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short-term outcomes of LT. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 10 2023 A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection e0287501 EN Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Haruto Yamada Department of Infectious Disease, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. Methods This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or noteprenone groups in a 1:1 ratio. We stratified patients by sex, age < and >= 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. Results One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/ 49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). Conclusion Teprenone afforded no clinical benefit. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Lysyl oxidase-like 4 exerts an atypical role in breast cancer progression that is dependent on the enzymatic activity that targets the cell-surface annexin A2 EN NI LUH GEDE YONI KOMALASARI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 LOXL1 and LOXL4 are novel target genes of the Zn²⁺-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells EN Daisuke HIRABAYASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 An observational study of the impact of immediate breast reconstruction on perioperative inflammatory cytokines EN Yuko MUKAI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1792-0981 26 5 2023 Evaluation of the accuracy of heart dose prediction by machine learning for selecting patients not requiring deep inspiration breath‑hold radiotherapy after breast cancer surgery 536 EN Ryo Kamizaki Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Masahiro Kuroda Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla Al‑Hammad Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nouha Tekiki Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hinata Ishizaka Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Kazuhiro Kuroda Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An‑Najah National University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Yuki Nakamitsu Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Masaki Hirano Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Yuki Muto Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Hiroki Ihara Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichi Sugiyama Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Increased heart dose during postoperative radiotherapy (RT) for left‑sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath‑hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left‑sided BC. However, treatment planning and DIBH for RT are laborious, time‑consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre‑select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right‑left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve‑receiver operating characteristic of 0.88, for a cut‑off value of 300 cGy. The present study suggested that ML can be used to pre‑select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1880-6546 73 1 2023 Connective tissue mast cells store and release noradrenaline 24 EN Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Yoshikawa Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Nagao Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mast cells are present in mucosal and connective tissues throughout the body. They synthesize and release a wide variety of bioactive molecules, such as histamine, proteases, and cytokines. In this study, we found that a population of connective tissue mast cells (CTMCs) stores and releases noradrenaline, originating from sympathetic nerves. Noradrenaline-storing cells, not neuronal fibers, were predominantly identified in the connective tissues of the skin, mammary gland, gastrointestinal tract, bronchus, thymus, and pancreas in wild-type mice but were absent in mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice. In vitro studies using bone marrow-derived mast cells revealed that extracellular noradrenaline was taken up but not synthesized. Upon ionomycin stimulation, noradrenaline was released. Electron microscopy analyses further suggested that noradrenaline is stored in and released from the secretory granules of mast cells. Finally, we found that noradrenaline-storing CTMCs express organic cation transporter 3 (Oct3), which is also known as an extraneuronal monoamine transporter, SLC22A3. Our findings indicate that mast cells may play a role in regulating noradrenaline concentration by storing and releasing it in somatic tissues. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient 553 559 EN Takahiro Murokawa Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Kenta Sui Department of Gastroenterological Surgery, Kochi Health Sciences Center Kazuhide Ozaki Department of Gastroenterological Surgery, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Hiroshi Yoshida Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School Case Report /10.18926/AMO/65979 Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer 517 525 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Original Article 10.18926/AMO/65974 We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 30 13 2023 Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma 8727 8734 EN Naoki Matsuda Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuma Iwata Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Hashimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Toji Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhito Takahashi Department of Sarcoma Medicine, Center for Sarcoma Multidisciplinary Treatment, Kameda Medical Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers. Methods　We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis. Results　As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively. Conclusions　CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-2623 65 8 2022 Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo 6039 6055 EN Negar Khazan Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Kyu Kwang Kim Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Jeanne N. Hansen Department of Pediatrics, University of Rochester Medical Center Niloy A. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Taylor Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Cameron W. A. Snyder Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Ravina Pandita Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Myla Strawderman Department of Biostatistics and Computational Biology, University of Rochester Medical Center Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ye Jian Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nicholas Battaglia Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Naohiro Yano Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University Yuki Teramoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Leggy A. Arnold Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee Russell Hopson Department of Chemistry, Brown University Keshav Kishor Department of Chemistry, Birla Institute of Technology Sneha Nayak Department of Chemistry, Birla Institute of Technology Debasmita Ojha Department of Chemistry, Birla Institute of Technology Ashoke Sharon Department of Chemistry, Birla Institute of Technology John M. Ashton Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center Jian Wang Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Michael T. Milano Department of Radiation Oncology, University of Rochester Medical Center Hiroshi Miyamoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center David C. Linehan Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Scott A. Gerber Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nada Kawar Center for Breast Health and Gynecologic Oncology, Mercy Medical Center Ajay P. Singh Rutgers, The State University of New Jersey Erdem D. Tabdanov CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University Nikolay V. Dokholyan Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peter W. Jurutka School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center Nina F. Schor Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center Rachael B. Rowswell-Turner Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Rakesh K. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Richard G. Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 5 2023 Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 e0285273 EN Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Junichi Soh Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terazaki Department of Respiratory S0urgery, Saga-Ken Medical Centre Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. Methods Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. Results We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). Conclusion Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1198-0052 30 8 2023 Mean Heart Dose Prediction Using Parameters of Single-Slice Computed Tomography and Body Mass Index: Machine Learning Approach for Radiotherapy of Left-Sided Breast Cancer of Asian Patients 7412 7424 EN Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hinata Ishizaka Radiological Technology, Graduate School of Health Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Deep inspiration breath-hold (DIBH) is an excellent technique to reduce the incidental radiation received by the heart during radiotherapy in patients with breast cancer. However, DIBH is costly and time-consuming for patients and radiotherapy staff. In Asian countries, the use of DIBH is restricted due to the limited number of patients with a high mean heart dose (MHD) and the shortage of radiotherapy personnel and equipment compared to that in the USA. This study aimed to develop, evaluate, and compare the performance of ten machine learning algorithms for predicting MHD using a patient's body mass index and single-slice CT parameters to identify patients who may not require DIBH. Machine learning models were built and tested using a dataset containing 207 patients with left-sided breast cancer who were treated with field-in-field radiotherapy with free breathing. The average MHD was 251 cGy. Stratified repeated four-fold cross-validation was used to build models using 165 training data. The models were compared internally using their average performance metrics: F2 score, AUC, recall, accuracy, Cohen's kappa, and Matthews correlation coefficient. The final performance evaluation for each model was further externally analyzed using 42 unseen test data. The performance of each model was evaluated as a binary classifier by setting the cut-off value of MHD & GE; 300 cGy. The deep neural network (DNN) achieved the highest F2 score (78.9%). Most models successfully classified all patients with high MHD as true positive. This study indicates that the ten models, especially the DNN, might have the potential to identify patients who may not require DIBH. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0902-0063 37 11 2023 Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation e15077 EN Yujiro Kubo Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Toshio Shiotani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kei Matsubara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kohei Hashimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kazuhiko Shien Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Hiromasa Yamamoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Introduction: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT). Methods: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated. Results: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = －.36, P = .0031), the forced vital capacity (r = －.27, P = .027), and the total lung capacity (r = －.40, P < .001) were seen at the time of CLAD diagnosis. Conclusion: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT. No potential conflict of interest relevant to this article was reported.

AME Publishing Company Acta Medica Okayama 2072-1439 15 9 2023 Long-term management and outcome of lung transplantation in Japan 5182 5194 EN Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kei Matsubara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Megumi Ishihara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital The long-term survival after lung transplantation (LT) is favorable in Japan. However, longterm survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2324-7096 11 2023 Bilateral Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the Literature EN Toshihiko Matsuo Okayama University Takehiro Tanaka Okayama University Kazuya Okada Kurashiki Central Hospital Kenji Notohara Kurashiki Central Hospital Keiko Fujii Okayama University Hospital Nobuharu Fujii Okayama University Hospital A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 18794068 14 5 2023 Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee 101485 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Inoue Department of Obstetrics and Gynecology, University of Fukui Ken Sugimoto Department of General Geriatric Medicine, Kawasaki Medical School Chie Tanaka Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine Keiko Murofushi Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Toru Okuyama Department of Psychiatry / Palliative Care Center, Nagoya City University West Medical Center Shigeaki Watanuki National Center for Global Health and Medicine, National College of Nursing Chiyo K. Imamura Advanced Cancer Translational Research Institute, Showa University Daisuke Sakai Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine Naomi Sakurai Cancer Solutions Co.,Ltd Kiyotaka Watanabe Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University Kazuo Tamura NPO Clinical Hematology/Oncology Treatment Study Group Toshiaki Saeki Breast Oncology Service, Saitama Medical University International Medical Center Hiroshi Ishiguro Breast Oncology Service, Saitama Medical University International Medical Center Introduction: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved. Materials and Methods: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions. Discussion: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2045-2322 12 1 2022 Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing 20628 EN Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Furukawa Clinical Laboratory, Okayama University Hospital Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kouhei Ageta Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rumi Matsuo Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihito Higashikage Clinical Laboratory, Okayama University Hospital Takao Hikita Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Yokokura Yokokura Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (>30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p<0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2045-2322 13 1 2023 Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array 8912 EN Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Shiotani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. Delta eGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the Delta eGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2042-0226 20 7 2023 The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis 714 738 EN Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Breast cancer is the most prevalent cancer worldwide, and metastasis is the leading cause of death in cancer patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes. MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages (TAMs), and it became a candidate target of clinical intervention; however, the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1. The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues, including breast cancers. Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established. The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung, bone, and brain was examined in mouse breast cancer models. The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone. Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported. In the present manuscript, we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma 331 334 EN Mototsugu Watanabe Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Case Report /10.18926/AMO/65503 Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2399-3642 6 1 2023 NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism 596 EN Nobuhiro Okada Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Chihiro Ueki Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Masahiro Shimazaki Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Goki Tsujimoto Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Susumu Kohno Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University Hayato Muranaka Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University Kiyotsugu Yoshikawa Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts Chiaki Takahashi Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University Two splicing variants exist in NFYA that exhibit high expression in many human tumour types. The balance in their expression correlates with prognosis in breast cancer, but functional differences remain unclear. Here, we demonstrate that NFYAv1, a long-form variant, upregulates the transcription of essential lipogenic enzymes ACACA and FASN to enhance the malignant behavior of triple-negative breast cancer (TNBC). Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior in vitro and in vivo, indicating that the NFYAv1-lipogenesis axis is essential for TNBC malignant behavior and that the axis might be a potential therapeutic target for TNBC. Furthermore, mice deficient in lipogenic enzymes, such as Acly, Acaca, and Fasn, exhibit embryonic lethality; however, Nfyav1-deficient mice exhibited no apparent developmental abnormalities. Our results indicate that the NFYAv1-lipogenesis axis has tumour-promoting effects and that NFYAv1 may be a safe therapeutic target for TNBC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Impact of Immediate Breast Reconstruction on Survival of Breast Cancer Patients: A Single-Center Observational Study 281 290 EN Yuko Mukai Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima Citizens Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yohei Kitaguchi Department of Plastic and Reconstructive Surgery, Okayama University Hospital Miho Saiga Department of Plastic and Reconstructive Surgery, Okayama University Hospital Satoko Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article /10.18926/AMO/65493 Although immediate breast reconstruction following mastectomy has become increasingly common, its oncological safety has been debated. We enrolled patients with breast cancer who underwent surgery at Okayama University Hospital between 2007 and 2013. The primary outcome was relapse-free survival (RFS). Secondary outcomes were overall survival and the duration from the surgery to the initiation of adjuvant chemotherapy. We divided into immediate breast reconstruction, mastectomy alone, and breast conservative surgery groups. Outcomes were compared using Cox’s regression analysis. A total of 614 patients were included (reconstruction: 125, mastectomy: 128, breast conservative surgery: 361). The median follow-up duration was 79.0±31.9 months. The immediate-reconstruction patients were younger, had more lymph node metastases, and more often received postoperative chemotherapy. The RFS was better after the breast conservative surgery compared to after reconstruction (hazard ratio 0.33, 95% confidence interval: 0.144-0.763). The proportion of local recurrence was highest in the reconstruction group. No patients in the reconstruction group underwent postoperative radiation therapy. However, reconstruction did not affect overall survival or the time to the initiation of adjuvant chemotherapy. Surgeons should explain the risks of breast reconstruction to their patients preoperatively. Careful long-term follow-up is required after such procedures. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2405-8440 9 4 2023 Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantation e14903 EN Toshio Shiotani Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Organ Transplant Center, Okayama University Hospital Yasuaki Tomioka Organ Transplant Center, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Shin Tanaka Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of General Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital Background: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT). Methods: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD. Results: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89. Conclusion: Circulating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Predictive value of immune genomic signatures from breast cancer cohorts containing data for both response to neoadjuvant chemotherapy and prognosis after surgery EN YIDAN ZHU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer EN CHUNNING LI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2051-3380 11 6 2023 Pulmonary alveolar proteinosis after lung transplantation: Two case reports and literature review e01160 EN Shinichi Kawana Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Dai Shimizu Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kei Matsubara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Noboru Hattori Department of Molecular and Internal Medicine, Hiroshima University, Graduate School of Biomedical and Health Sciences Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Pulmonary alveolar proteinosis (PAP) affecting transplanted lungs is not well recognized. Herein, we report two cases of PAP after lung transplantation (LTx). The first case was a 4-year-old boy with hereditary pulmonary fibrosis who underwent bilateral LTx and presented with respiratory distress on postoperative day (POD) 23. He was initially treated for acute rejection, died due to infection on POD 248, and was diagnosed with PAP at autopsy. The second case involved a 52-year-old man with idiopathic pulmonary fibrosis who underwent bilateral LTx. On POD 99, chest computed tomography revealed ground-glass opacities. Bronchoalveolar lavage and transbronchial biopsy led to a diagnosis of PAP. Follow-up with immunosuppression tapering resulted in clinical and radiological improvement. PAP after lung transplantation mimics common acute rejection; however, is potentially transient or resolved with tapering immunosuppression, as observed in the second case. Transplant physicians should be aware of this rare complication to avoid misconducting immunosuppressive management. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2168-8184 15 2 2023 A Seat Belt Injury Causing a Large Breast Hematoma: A Case Report e35440 EN Shunki Yamamoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kosaki Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Uehara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seat belts with shoulder restraints have decreased the frequency of life-threatening severe chest trauma caused by car accidents. However, the introduction of seat belt legislation has led to an increase in a specific pattern of blunt trauma known as seat belt syndrome, which includes rib, clavicle, spine, and sternum fractures, as well as rupture of hollow pelvic and abdominal viscera, mesenteric tears, and major vessel injuries. The shoulder restraint part of the three-point seat belt commonly rests near or over the female and male breast. A 54-year-old female presented to our emergency department complaining of swelling and pain in her left breast immediately after a traffic accident. The patient had used a seat belt with a shoulder restraint. Bruising was noted along her chest where there had been seat belt contact. Her breast hematoma was most likely caused by breast tissue compression between her rib and the seat belt. Contrast-enhanced computed tomography demonstrated a sizable breast hematoma with active arterial contrast material extravasation, as well as multiple left rib fractures. The patient was conservatively treated with analgesic and anti-inflammatory drugs. Complete resolution was achieved, and her breast returned to its normal appearance. Although endovascular treatment and surgical hemostasis have been proposed for the treatment of breast injuries with active bleeding, conservative treatment such as compression hemostasis may be feasible. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 10 2 2022 Association between Overall Survival and Activities of Daily Living in Patients with Spinal Bone Metastases 350 EN Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Haruyoshi Katayama Department of Orthopaedic Surgery, Okayama University Hospital Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Objective: This study aimed to investigate the association between overall survival (OS) and activities of daily living (ADL) in patients with skeletal-related events. In this study, 265 patients whose clinical parameters were available before radiotherapy were investigated. Methods: Age, sex, ADL, pain, the primary site, spinal level of bone metastases, spinal instability, treatment strategy, including chemotherapy or palliative treatment, and OS were investigated. ADL patients with a Barthel index of >= 90 were classified as the high ADL group, while those with a score < 90 were classified as the low ADL group. For OS, patients surviving >= 160 days were classified as the non-poor prognosis group, and those who survived <160 days were classified as the poor prognosis group. Results: Age, sex, ADL, pain, the primary site, and treatment strategy for OS were different between the two groups (p < 0.1). Logistic regression analysis revealed that ADL, the primary site, and treatment strategy were significant predictors of OS (p < 0.05). High ADL, breast cancer, and chemotherapy had a positive effect on OS. Conclusions: It is suggested that improvements may be obtained by performing rehabilitation interventions to maintain and improve ADL, by constructing a system for monitoring spinal bone metastases with images before ADL decreases, and by performing interventions such as changes in treatment methods such as RT or surgery at appropriate times. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2234-943X 13 2023 Lysyl oxidase-like 4 exerts an atypical role in breast cancer progression that is dependent on the enzymatic activity that targets the cell-surface annexin A2 1142907 EN Ni Luh Gede Yoni Komalasari Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Youyi Chen Department of General Surgery & Bio-Bank of General Surgery, TheFourth Affiliated Hospital of Harbin Medical University Yoshihiko Sakaguchi Department of Microbiology, Kitasato University School of Medicine Yuma Gohara Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ich Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences I Made Winarsa Ruma Faculty of Medicine, Udayana University I Wayan Sumardika Faculty of Medicine, Udayana University Jin Zhou Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: LOX family members are reported to play pivotal roles in cancer. Unlike their enzymatic activities in collagen cross-linking, their precise cancer functions are unclear. We revealed that LOXL4 is highly upregulated in breast cancer cells, and we thus sought to define an unidentified role of LOXL4 in breast cancer. Methods: We established the MDA-MB-231 sublines MDA-MB-231-LOXL4 mutCA and -LOXL4 KO, which stably overexpress mutant LOXL4 that loses its catalytic activity and genetically ablates the intrinsic LOXL4 gene, respectively. In vitro and in vivo evaluations of these cells’ activities of cancer outgrowth were conducted by cell-based assays in cultures and an orthotopic xenograft model, respectively. The new target (s) of LOXL4 were explored by the MS/MS analytic approach. Results: Our in vitro results revealed that both the overexpression of mutCA and the KO of LOXL4 in cells resulted in a marked reduction of cell growth and invasion. Interestingly, the lowered cellular activities observed in the engineered cells were also reflected in the mouse model. We identified a novel binding partner of LOXL4, i.e., annexin A2. LOXL4 catalyzes cell surface annexin A2 to achieve a cross-linked multimerization of annexin A2, which in turn prevents the internalization of integrin β-1, resulting in the locking of integrin β-1 on the cell surface. These events enhance the promotion of cancer cell outgrowth. Conclusions: LOXL4 has a new role in breast cancer progression that occurs via an interaction with annexin A2 and integrin β-1 on the cell surface. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Prolonged Sedentary Bouts Are Critically Involved in All-Cause Mortality in Patients on Chronic Hemodialysis: A Prospective Cohort Study 139 145 EN Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Kazuhiro Ujike Innoshima General Hospital Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Kiichi Koumoto Innoshima General Hospital Original Article /10.18926/AMO/65143 We investigated the link between prolonged sedentary bouts and all-cause mortality in patients on chronic hemodialysis, using a prospective cohort. A total of 104 outpatients on chronic hemodialysis from 2013 to 2019, aged 71.4±11.4 years, were enrolled. Prolonged sedentary bouts (≥ 30 min and ≥60 min) (min and bouts) and relative prolonged sedentary bouts (≥ 30 min and ≥ 60 min) (%) on the patients’ non-hemodialysis days were measured by a tri-accelerometer, and we also analyzed the patients’ clinical parameters. The relationship between prolonged sedentary bouts and all-cause mortality was evaluated by a survival analysis and the Cox proportional hazard model. Thirty-five patients died during the follow-up period. A Kaplan-Meier analysis detected significant differences in the survival rate between two groups stratified by the median for all prolonged sedentary-bout parameters. After the adjustment for confounding factors, all of the prolonged sedentary-bout parameters were determinant factors for all-cause mortality. These results indicate that prolonged sedentary bouts on non-hemodialysis days were closely related to all-cause mortality in the patients on hemodialysis. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2234-943X 13 2023 LOXL1 and LOXL4 are novel target genes of the Zn2+-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells 1142886 EN Daisuke Hirabayashi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Maruyama Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Youyi Chen Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University Ni Luh Gede Yoni Komalasari Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Gohara Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jin Zhou Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology I. Made Winarsa Ruma Faculty of Medicine, Udayana University I. Wayan Sumardika Faculty of Medicine, Udayana University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: EMT has been proposed to be a crucial early event in cancer metastasis. EMT is rigidly regulated by the action of several EMT-core transcription factors, particularly ZEB1. We previously revealed an unusual role of ZEB1 in the S100A8/A9-mediated metastasis in breast cancer cells that expressed ZEB1 at a significant level and showed that the ZEB1 was activated on the MCAM-downstream pathway upon S100A8/A9 binding. ZEB1 is well known to require Zn2+ for its activation based on the presence of several Zn-finger motifs in the transcription factor. However, how Zn2+-binding works on the pleiotropic role of ZEB1 through cancer progression has not been fully elucidated. Methods: We established the engineered cells, MDA-MB-231 MutZEB1 (MDA-MutZEB1), that stably express MutZEB1 (Delta Zn). The cells were then evaluated in vitro for their invasion activities. Finally, an RNA-Seq analysis was performed to compare the gene alteration profiles of the established cells comprehensively. Results: MDA-MutZEB1 showed a significant loss of the EMT, ultimately stalling the invasion. Inclusive analysis of the transcription changes after the expression of MutZEB1 (Delta Zn) in MDA-MB-231 cells revealed the significant downregulation of LOX family genes, which are known to play a critical role in cancer metastasis. We found that LOXL1 and LOXL4 remarkably enhanced cancer invasiveness among the LOX family genes with altered expression. Conclusions: These findings indicate that ZEB1 potentiates Zn2+-mediated transcription of plural EMT-relevant factors, including LOXL1 and LOXL4, whose upregulation plays a critical role in the invasive dissemination of breast cancer cells. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0163-4453 85 4 2022 Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people 436 480 EN Hideharu Hagiya Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takao Hikita Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaki Asada Departments of Medical Education, Kurashiki Central Hospital Takashi Yorifuji Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 The Efficacy of Inflammatory and Immune Markers for Predicting the Prognosis of Patients with Stage IV Breast Cancer 37 43 EN Kosho Yamanouchi Department of Surgery, National Hospital Organization, Nagasaki Medical Center Shigeto Maeda Department of Surgery, National Hospital Organization, Nagasaki Medical Center Original Article /10.18926/AMO/64360 Systemic therapy for stage IV breast cancer is usually an initial treatment and is based on findings regarding biomarkers (e.g., hormone receptors and human epidermal growth factor receptor-2 [HER2]). However, the response to therapy and outcomes sometime differ among patients with similar prognostic factors including grade, hormone receptor, HER2, and more. We conducted retrospective analyses to evaluate the correlations between the overall survival (OS) of 46 stage IV breast cancer patients and (i) the peripheral absolute lymphocyte count (ALC) and (ii) composite blood cell markers. The peripheral blood cell markers included the neutrophil- to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the most recently introduced indicator, the pan-immune-inflammatory value (PIV). The SIRI and PIV showed prognostic impacts on the patients: those with a low SIRI or a low PIV showed significantly better OS than those with a high SIRI (5-year, 66.0% vs. 35.0%, p<0.05) or high PIV (5-year, 68.1% vs. 38.5%, p<0.05), respectively. This is the first report indicating the possible prognostic value of the PIV for OS in patients with stage IV breast cancer. Further studies with larger numbers of patients are necessary for further clarification. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Safety and Efficacy of a Well-Fitting Brassiere after Breast Reconstruction: A Qualitative Study 11 19 EN Satoko Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Miho Saiga Department of Plastic and Reconstructive Surgery, Okayama University Hospital Takayuki Motoki Department of General Surgery, Okayama Saiseikai General Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Original Article /10.18926/AMO/64356 The importance of a well-fitted, comfortable brassiere to overall quality of life after breast reconstruction has not been evaluated. Our aim was to determine the impact of a semi-customized brassiere on patients’ health-related quality of life after breast reconstruction. The subjects were prospective patients with mastectomy who were to undergo immediate or delayed breast reconstruction at our hospital. After surgery, a professional bra fitter sized each patient for a semi-customized brassiere and provided follow-up consultations. A self-reported questionnaire on breast aesthetics, postoperative pain, and satisfaction was used to assess the primary outcomes. Data were prospectively collected at baseline (before surgery) and at 1, 3, 6, and 12 months after surgery and analyzed. Forty-six patients (50 breasts) were included in the analysis. Consistent wearing of the brassiere reduced pain (p<0.05), with good overall satisfaction (p<0.001). Aesthetic scores on breast shape and size were higher with than without the custom brassiere at 3 months (p=0.02) and 6 months (p=0.03) after surgery. Wearing the brassiere reduced anxiety at all time points of measurement. A well-fitting brassiere ensured safety and provided a high degree of satisfaction without anxiety for patients after breast reconstruction. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1198-0052 30 1 2023 Characteristics of Postoperative Patients with Breast Cancer Aged 65 Years and Older 673 680 EN Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Ritsuko Tominaga Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Hideaki Kurokawa Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center, Masaki Okamoto Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center, Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Kenjiro Aogi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Shozo Ohsumi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Objective: This study aimed to compare postoperative patients with breast cancer aged >= 65 years with those aged <65 years and clarify the characteristics of postoperative patients with breast cancer aged >= 65. Methods: In total, 376 patients in whom we were able to evaluate survey items one month after surgery were included in the study. Comorbidity, including diabetes mellitus and hypertension, shoulder range of motion (ROM), upper-limb function, and psychological problems, was evaluated. Results: Hypertension and diabetes mellitus were significantly higher in patients aged >= 65 years (the elderly group) than in those aged <65 years (the non-elderly group) (p < 0.05). Preoperative shoulder flexion ROM was significantly restricted in the elderly group compared with the non-elderly group (p < 0.05). Preoperative shoulder abduction ROM was significantly restricted in the elderly group compared with the non-elderly group (p < 0.05). At one month after surgery, upper-limb function was more impaired in the non-elderly group than in the elderly group (p < 0.05). In both groups, both ROM and upper-limb function were significantly impaired one month after surgery compared with before surgery (p < 0.05). Conclusions: Postoperative patients with breast cancer aged >= 65 years should be careful about risk management and intervention during rehabilitation. Preoperative evaluation of shoulder ROM should be performed because patients aged >= 65 years have limited ROM before surgery. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 15 2 2023 Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators 468 EN Yuze Wang Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuehua Chen Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Hamada Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Simple Summary Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate the possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo lung metastatic model. We found that highly metastatic TNBC cells have limited iron metabolism and can be more effectively targeted by iron chelators. Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1742-4801 2022 2022 Surgical site infections in thyroid and parathyroid surgery in Japan: An analysis of the Japan Nosocomial Infections Surveillance database from 2013 to 2020 EN Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Shinya Saito Graduate School of Health Sciences, Okayama University Surgical site infections (SSIs) after thyroid surgery are rare complications, with incidence rates of 0.3%-1.6%. Using a Japanese database, we conducted exploratory analyses on the incidence of SSIs, investigated the incidence of SSIs by the National Nosocomial Infections Surveillance risk index, and identified the causative bacteria of SSIs. SSIs occurred in 50 (0.7%) of 7388 thyroid surgery cases. Risk index-0 patients had the lowest incidence rate of SSIs (0.41%). The incidence of SSIs in risk index-1 patients was 3.05 times the incidence of SSIs in risk index-0 patients. The rate of SSI occurrence for risk index-2 patients was 4.22 times the rate of SSI occurrence for risk index-0 patients. Thirty-one bacterial species were identified as the cause of SSIs in thyroid surgery cases, of which 12 (38.7%) SSIs were caused by Staphylococcus aureus and Staphylococcus epidermidis. Of the nine SSIs caused by Staphylococcus aureus, 55.6% (five cases) were attributed to methicillin-resistant Staphylococcus aureus. Therefore, routine prophylactic antibiotic administration should be avoided, while the target for administration should be narrowed, according to the SSI risk. Administration of prophylactic antibiotics, such as 2 g piperacillin or 1 g cefazolin, is considered appropriate. No potential conflict of interest relevant to this article was reported.

American Thoracic Society Acta Medica Okayama 1044-1549 67 6 2022 Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis through IL-1β Inhibition 654 665 EN Junko Itano Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiko Taniguchi Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Senoo Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Yuka Gion Department of Medical Technology, Okayama University Graduate School of Health Sciences Yuria Egusa Department of Medical Technology, Okayama University Graduate School of Health Sciences Lili Guo Department of Medical Technology, Okayama University Graduate School of Health Sciences Naohiro Oda Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kota Araki Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Medical Technology, Okayama University Graduate School of Health Sciences Shinichi Toyooka Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Neuropeptide Y (NPY), a 36 amino acid residue polypeptide distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of NPY on pulmonary fibrosis. NPY-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine concentrations, and morphological morphometry of the lungs were analyzed. Serum NPY concentrations were also measured in patients with idiopathic pulmonary fibrosis and healthy control subjects. NPY-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1 beta concentrations in the lungs compared with wild-type mice. Exogenous NPY treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1 beta concentrations in the lungs. Moreover, IL-1 beta neutralization in NPY-deficient mice attenuated the fibrotic changes. NPY decreased IL-1 beta release, and Y1 receptor antagonists inhibited IL-1 beta release and induced epithelial-mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower NPY and greater IL-1 beta concentrations in the serums compared with healthy control subjects. NPY expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that NPY plays a protective role against pulmonary fibrosis by suppressing IL-1 beta release, and manipulating the NPY-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2306-5354 9 11 2022 Functional Blockage of S100A8/A9 Ameliorates Ischemia-Reperfusion Injury in the Lung 673 EN Kentaro Nakata Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohisa Sakaue Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuhei Komoda Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Dai Shimizu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (1) Background: Lung ischemia-reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 An Evaluation of the Efficacy of Compression Therapy Using Sleeves and Stockings to Prevent Docetaxel-induced Peripheral Neuropathy in Breast Cancer Patients 689 694 EN Kosho Yamanouchi Department of Surgery, Nagasaki University Graduate School of Biomedical Science Sayaka Kuba Department of Surgery, Nagasaki University Graduate School of Biomedical Science Megumi Matsumoto Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Hiroshi Yano Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Michi Morita Department of Surgery, Nagasaki University Graduate School of Biomedical Science Chika Sakimura Department of Surgery, Nagasaki University Graduate School of Biomedical Science Ryota Otsubo Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Masaaki Hidaka Department of Surgery, Nagasaki University Graduate School of Biomedical Science Takeshi Nagayasu Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Susumu Eguchi Department of Surgery, Nagasaki University Graduate School of Biomedical Science Original Article /10.18926/AMO/64119 Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients 661 671 EN Yuko Abe Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruto Taira Department of Breast and Endocrine surgery, Kawasaki Medical School Hospital Kosuke Kashiwabara Clinical Research Promotion Center, University of Tokyo Hospital Junji Tsurutani Advanced Cancer Translational Research Institute, Showa University Masahiro Kitada Breast Disease Center, Asahikawa Medical University Hospital Masato Takahashi Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center Hiroaki Kato Department of Breast Surgery, Teine Keijinkai Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Hospital Eiko Sakata Department of Breast Surgery, Niigata City General Hospital Yoichi Naito Department of Medical Oncology, National Cancer Center Hospital East Yoshie Hasegawa Department of Breast Surgery, Hachinohe City Hospital Tsuyoshi Saito Department of Breast Surgery, Japanese Red Cross Saitama Hospital Tsutomu Iwasa Department of Medical Oncology, Kindai University Faculty of Medicine Tsutomu Takashima Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine Tomohiko Aihara Breast Center, Aihara Hospital Hirofumi Mukai Department of Medical Oncology, National Cancer Center Hospital East Fumikata Hara Breast Oncology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research Tadahiko Shien Department of Breast and Endocrine surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast surgery, Kawasaki Medical School General Medical Center Shinichi Toyooka Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64116 Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001－3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Knockdown of LncRNA SBF2-AS1 Inhibited Gastric Cancer Tumorigenesis via the Wnt/LRP5 Signaling Pathway 625 633 EN Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine) Qingmei Li Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine) Ye Wang Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine) Yunjie Ge Department of Healthcare Internal Medicine, Affiliated Qingdao Municipal Hospital of Qingdao University Original Article /10.18926/AMO/64112 This investigation aimed to uncover the impact of a long noncoding RNA, SET-binding factor 2 antisense RNA1 (SBF2-AS1) on the malignant progression of gastric cancer (GC) and to further explore its underlying mechanism. SBF2-AS1 expression was quantified by qRT-PCR in GC cell lines and GC tissues. In vitro loss-of-function studies of SBF2-AS1, accompanied by flow cytometry, CCK-8, and cell invasion tests, were applied to elucidate the impact of SBF2-AS1 on the tumor progression of GC cells. Finally, Western blotting and a luciferase assay were used to detect WNT/LRP5 signaling pathway activation. SBF2-AS1 was aberrantly expressed in GC cell lines (p<0.05) and GC tissues (p<0.05). Cell invasive and proliferative capabilities were inhibited via SBF2-AS1 knockdown, resulting in apoptosis of NCI-N87 and MKN74 cells. Additionally, online database analysis uncovered a positive correlation between SBF2-AS1 and the Wnt/LRP5 signaling pathway (p<0.05). SBF2-AS1 knockdown blocked the Wnt/LRP5 signaling pathway, whereas the effects of SBF2-AS1 knockdown on the malignant genotype of MKN74 as well as NCI-N87 cells were partially restored by triggering the Wnt/ LRP5 signaling pathway. High expression of SBF2-AS1 was found in GC, the malignant progression of which was repressed via SBF2-AS1 knockdown by inhibiting the Wnt/LRP5 signaling pathway. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development EN Miwa FUJIHARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer EN Yukiko KAJIWARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Influences of preoperative metformin on immunological factors in early breast cancer EN Takahiro TSUKIOKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: a Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients EN Yuko ABE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma 593 596 EN Taku Noumi Department of Respiratory Medicine, Okayama University Hospital Hiromi Watanabe Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiichiro Ninomiya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Yuka Kato Department of Respiratory Medicine, Okayama University Hospital Masanori Fujii Department of Respiratory Medicine, Okayama University Hospital Masahiro Tabata Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Hotta Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Case Report 10.18926/AMO/64041 We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 11 20 2022 Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect 3307 EN Abdul Basith Fithroni Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazuko Kobayashi Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hirotaka Uji Department of Material Chemistry, Graduate School of Engineering, Kyoto University Manabu Ishimoto Fukushima SiC Applied Engineering Inc. Masaru Akehi Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Matsuura Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 23 19 2022 Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model 11035 EN Tsukasa Shigehiro Research Institute for Biomedical Sciences, Tokyo University of Science Maho Ueno Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Mayumi Kijihira Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Ryotaro Takahashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Chiho Umemura Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Eman A. Taha Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Chisaki Kurosaka Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Megumi Asayama Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Hiroshi Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Junko Masuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 23 18 2022 Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells 10300 EN Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Wake Department of Pharmacology, Kindai University Faculty of Medicine Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University I. Made Winarsa Ruma Faculty of Medicine, Udayana University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Gohara Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ni Luh Gede Yoni Komalasari Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences I. Wayan Sumardika Faculty of Medicine, Udayana University Youyi Chen Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Eisaku Kondo Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Nishibori Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1465-5411 24 1 2022 Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer 60 EN Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Kondo Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken-Ichi Yamamoto Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Patients with triple-negative breast cancer (TNBC) often have poorer prognosis than those with other subtypes because of its aggressive behaviors. Cancer cells are heterogeneous, and only a few highly metastatic subclones metastasize. Although the majority of subclones may not metastasize, they could contribute by releasing factors that increase the capacity of highly metastatic cells and/or provide a favorable tumor microenvironment (TME). Here, we analyzed the interclonal communication in TNBC which leads to efficient cancer progression, particularly lung metastasis, using the polyclonal murine 4T1 BC model. Methods We isolated two 4T1 subclones, LM.4T1 and HM.4T1 cells with a low and a high metastatic potential, respectively, and examined the effects of LM.4T1 cells on the behaviors of HM.4T1 cells using the cell scratch assay, sphere-forming assay, sphere invasion assay, RT-qPCR, and western blotting in vitro. We also examined the contribution of LM.4T1 cells to the lung metastasis of HM.4T1 cells and TME in vivo. To identify a critical factor which may be responsible for the effects by LM.4T1 cells, we analyzed the data obtained from the GEO database. Results Co-injection of LM.4T1 cells significantly augmented lung metastases by HM.4T1 cells. LM.4T1-derived exosomes promoted the migration and invasion of HM.4T1 cells in vitro, and blocking the secretion of exosome abrogated their effects on HM.4T1 cells. Analyses of data obtained from the GEO database suggested that Wnt7a might be a critical factor responsible for the enhancing effects. In fact, a higher level of Wnt7a was detected in LM.4T1 cells, especially in exosomes, than in HM.4T1 cells, and deletion of Wnt7a in LM.4T1 cells significantly decreased the lung metastasis of HM.4T1 cells. Further, treatment with Wnt7a increased the spheroid formation by HM.4T1 cells via activation of the PI3K/Akt/mTOR signaling pathway. Finally, infiltration of alpha SMA-positive fibroblasts and angiogenesis was more prominent in tumors of LM.4T1 cells and deletion of Wnt7a in LM.4T1 cells markedly reduced angiogenesis. Conclusions We demonstrated, for the first time, that a low metastatic subclone can enhance lung metastasis of highly metastatic subclone via exosomal Wnt7a and propose Wnt7a as a molecular target to treat TNBC patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives 479 483 EN Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reimi Sogawa Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Kayoko Hasuoka Department of Nursing, Okayama University Hospital Shuta Tomida Department of Center for Comprehensive Genomic Medicine, Okayama University Hospital Biobank, Okayama University Hospital Mashu Futagawa Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Yusaku Urakawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Kochi Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report /10.18926/AMO/63908 A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient’s daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer 399 408 EN Yukiko Kajiwara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Iwamoto Departments of Breast and Endocrine Surgery, Okayama University Hospital Yidan Zhu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Kochi Departments of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Departments of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Departments of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Departments of Breast and Endocrine Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63894 According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2－) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatmentgene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Effects of Tanden Breathing on Constipation: A Randomized Controlled Trial 391 398 EN Hiroshi Habu Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akiko Tokinobu Department of Epidemiology and Public Health, Ehime University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63893 Tanden breathing, an ancient health technique, involves expiratory abdominal pressure breathing is practiced in Japan. In this study we examined the ability of Tanden breathing to relieve constipation. The study was designed as a stratified-block randomized controlled trial enrolling 20 participants. Nineteen were female and one was male, none were elderly. During the 6-week intervention period, the participants performed video-guided Tanden breathing about 10 min once day. We evaluated constipation using the Constipation Assessment Scale (CAS). There were significant differences in the mean CAS score between time points (baseline, 3 weeks after baseline, 6 weeks after baseline), groups (intervention and control), and their interaction (time×group) using repeated-measures analysis of variance. The control group showed no change in the mean CAS score; the mean CAS scores of the intervention group changed from 7.2 at baseline to 3.9 at 3 weeks and 3.1 at 6 weeks after baseline. A regression analysis of the difference in the mean CAS between baseline and 6 weeks later showed that the CAS of the intervention group was 4.3 points lower than that of the control group (95% confidence interval, 2.5-6.1). The results suggested that Tanden breathing is effective in relieving constipation among young women. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus 359 371 EN Sumie Hiramatsu-Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review /10.18926/AMO/63887 Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4426 12 8 2022 Robotic Mediastinal Tumor Resections: Position and Port Placement 1195 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science This study aimed to determine the optimal position and port placement during robotic resection for various mediastinal tumors. For anterior mediastinal tumors, total or extended thymectomy is commonly performed in the supine position using the lateral or subxiphoid approach. Although it is unclear which approach is better during robotic thymectomy, technical advantages of subxiphoid approach are beneficial for patients with myasthenia who require extended thymectomy. Partial thymectomy is performed in the supine position using a lateral approach. Superior, middle, and posterior mediastinal tumors are resected in the decubitus position using the lateral approach, whereas dumbbell tumor resection, which requires a posterior approach, can be performed in the prone position. The position and port placement should be chosen depending on the size, location, and aggressiveness of the tumor. In this study, we describe how to choose which of these different robotic approaches can be used based on our experience and previous reports. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2022 2022 Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast EN Kosuke Ochi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yin Min Thu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumiaki Takatsu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shimpei Tsudaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yidan Zhu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Nakata Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuaki Takeda Departments of Pharmacy, Okayama University Hospital Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiharu Okamoto Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction. No potential conflict of interest relevant to this article was reported.

ELSEVIER Acta Medica Okayama 2059-7029 7 4 2022 Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study (vol 6, 100191, 2021) EN K. Hotta Center for Innovative Clinical Medicine, Okayama University Hospital S. Saeki Department of Respiratory Medicine, Kumamoto University Hospital M. Yamaguchi Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center D. Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center A. Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital K. Tanaka Department of Respiratory Medicine, Kyushu University Hospital K. Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center K. Gemba Department of Respiratory Medicine, Chugoku Central Hospital M. Shiojiri Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Y. Kato Center for Innovative Clinical Medicine, Okayama University Hospital T. Ninomiya Department of Respiratory Medicine, Okayama University Hospital T. Kubo Department of Respiratory Medicine, Okayama University Hospital J. Kishimoto Center for Clinical and Translational Research, Kyushu University Hospital Y. Shioyama Clinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu University K. Katsui Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences J. Sasaki Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine K. Kiura Department of Respiratory Medicine, Okayama University Hospital K. Sugio Department of Thoracic and Breast Surgery, Oita University No potential conflict of interest relevant to this article was reported.

AME Publishing Company Acta Medica Okayama 2072-1439 2022 Lung recruitment after cardiac arrest during procurement of atelectatic donor lungs is a protective measure in lung transplantation EN Eito Niman Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshio Shiotani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Toji Department of Diagnostic Pathology, Okayama University Hospital Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model. Methods: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised. Results: The post-transplant PaO2/FiO(2) ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AlT group. Conclusions: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure. No potential conflict of interest relevant to this article was reported.