Wiley Acta Medica Okayama 0012-1592 68 3 2026 A Simple Method for RNA-Seq of Manually Isolated Chromatophores in Oryzias Fishes e70044 EN Makoto Goda Institute of Photonics Medicine, Hamamatsu University School of Medicine Asuka Miyagi Institute of Photonics Medicine, Hamamatsu University School of Medicine Keisuke Sugiwaka Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Masakatsu Watanabe Cellular and Structural Physiology Institute (CeSPI) and Graduate School of Pharmaceutical Sciences, Nagoya University Manabu Bessho‐Uehara Frontier Research Institute for Interdisciplinary Science, Tohoku University Masahiko Hibi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Atsushi Toyoda Comparative Genomics Laboratory, National Institute of Genetics Rieko Tanaka World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Satoshi Ansai Ushimado Marine Institute, Okayama University Hisashi Hashimoto Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University RNA sequencing (RNA-seq) has become an essential tool for analyzing gene expression and exploring cell type–specific transcriptomes. However, sample preparation and quality control remain challenging, as current approaches typically rely on dissecting tissues containing mixed cell populations or using flow cytometry to isolate fluorescently labeled cells. Here we present a simple and reliable method for RNA-seq of chromatophores (pigment cells) by manually isolating cells based on their natural pigmentation. We analyzed four chromatophore types―melanophores, xanthophores, iridophores, and leucophores―in medaka (Oryzias latipes). Remarkably, as few as 100 cells per type yielded reasonably high-quality transcriptomes sufficient to identify differentially expressed genes (DEGs). Furthermore, this method was successfully applied to a non-model medaka species, O. woworae, which shares the same four chromatophore types. Our approach enables efficient, low-cost, and cross-species transcriptome analysis of chromatophores without requiring transgenic markers or flow cytometry. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma 3303 EN Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Lan Inoki Department of Urology, Faculty of Medicine, Kindai University Mamoru Hashimoto Department of Urology, Faculty of Medicine, Kindai University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Kazumasa Komura Department of Urology, Kawasaki University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University JK-FOOT study group Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO–IO and IO–tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO–IO and IO–TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO–IO and IO–TKI. In bone metastases (n = 80), OS tended to favor IO–TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO–TKI (P = 0.011). IO–TKI may be a more appropriate first-line option than IO–IO for mRCC with bone or liver metastases, while efficacy is similar for other sites. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 24 1 2026 TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan EN Hiroyuki Wakiguchi Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Kunio Hashimoto Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences Masato Yashiro Department of Pediatrics, Okayama University Hospital Kenichi Nishimura Department of Pediatrics, Yokohama City University Graduate School of Medicine Takasuke Ebato Department of Pediatrics, Kitasato University Keiji Akamine Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center Yoji Uejima Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center Tomomi Sato Clinical Education Center for Physicians, Shiga University of Medical Science Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Junko Yasumura Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital Fumiko Okazaki Department of Pediatrics, Yamaguchi University Graduate School of Medicine Toshitaka Kizawa Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital Ryuhei Yasuoka Department of Pediatrics, Hamamatsu University School of Medicine Tomoaki Ishikawa Department of Pediatrics, Nara Medical University Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Yuji Fujita Department of Pediatrics, Dokkyo Medical University Naohiro Itoh Department of Pediatrics, Faculty of Medical Sciences, University of Fukui Asami Takasaki Department of Pediatrics, School of Medicine, University of Toyama Nodoka Sakurai Department of Pediatrics, NTT East Medical Center Sapporo Kazuo Suzuki Suzuki Kids Clinic Tasuku Tamai Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Naoki Hirano Department of Public Health and Epidemiology, Faculty of Medicine, Oita University Nami Okamoto Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.<br> Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.<br> Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively.<br> Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-5370 80 2025 Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial 103078 EN Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Motoko Yamaguchi Department of Hematological Malignancies, Mie University Graduate School of Medicine Yachiyo Kuwatsuka Department of Advanced Medicine, Nagoya University Hospital Kosei Matsue Division of Hematology/Oncology, Internal Medicine, Kameda Medical Center Keijiro Sato Department of Hematology, Nagano Red Cross Hospital Shigeru Kusumoto Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences Hirokazu Nagai Department of Hematology, National Hospital Organization Nagoya Medical Center Jun Takizawa Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine Noriko Fukuhara Department of Hematology and Rheumatology, Tohoku University Hospital Koji Nagafuji Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine Kana Miyazaki Department of Hematology and Oncology, Mie University Graduate School of Medicine Eiichi Ohtsuka Department of Hematology, Oita Prefectural Hospital Akinao Okamoto Department of Hematology, Fujita Health University School of Medicine Yasumasa Sugita Department of Hematology, Oami Municipal Hospital Toshiki Uchida Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Satoshi Kayukawa Department of Clinical Oncology, Nagoya Memorial Hospital Atsushi Wake Department of Hematology, Toranomon Hospital Kajigaya Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Yukio Kondo Department of Internal Medicine, Toyama Prefectural Central Hospital Akiko Meguro Division of Hematology, Tochigi Cancer Center Yoshihiro Kin Department of Hematology, Daini Osaka Police Hospital Yosuke Minami Department of Hematology, National Cancer Center Hospital East Daigo Hashimoto Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine Takahiro Nishiyama Division of Hematology, Ichinomiya Municipal Hospital Satoko Shimada Department of Pathology and Clinical Laboratories, Nagoya University Hospital Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Masataka Okamoto Department of Hematology, Fujita Health University School of Medicine Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Hitoshi Kiyoi Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Ritsuro Suzuki Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine Shigeo Nakamura Department of Pathology and Clinical Laboratories, Nagoya University Hospital Tomohiro Kinoshita Department of Hematology and Cell Therapy, Aichi Cancer Center Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi).<br> Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165).<br> Findings With a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1).<br> Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients.<br> Funding This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-9861 779 2026 Comparison of bioavailability of quercetin and its structural analogs in mice 110775 EN Nozomi Maeda Graduate School of Environmental and Life Science, Okayama University Atsushi Hashimoto Graduate School of Environmental and Life Science, Okayama University Ryosei Morita Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Flavonoids are thought to provide beneficial effects on health. However, there are still uncertainties regarding their bioavailability. In this study, we investigated the bioavailability of 6 flavonoids, galangin, kaempferol, quercetin, myricetin, fisetin, and luteolin, by oral administration to mice. Analysis of plasma concentrations of free flavonoids after deconjugation by LC-MS/MS revealed that all flavonoids were rapidly absorbed after administration. Among 6 flavonoids, kaempferol and fisetin showed high absorbed amounts in blood plasma. With the LogP value of the two flavonoids as the maximum value, the amount absorbed decreased for both lower and higher LogP values. The results of the tissue distribution of galangin, kaempferol, and quercetin suggested that the order of fastest movement from the stomach to the small intestine was kaempferol > quercetin > galangin. In addition, the amount of kaempferol and quercetin distributed in the liver was greater than that of galangin. These results suggest that the bioavailability of flavonoids varies with the slight structural differences, possibly due to differences in their rapid accessibility to the small intestine that is the primary site of absorption and metabolism within the body. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702) EN Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A–E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically “cold” pancreatic tumors into “hot” tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte–macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-445X 15 2 2026 A Study on the Development of an Image Classification System for Urban Sprawl Areas in Japan 275 EN Ryota Hemmi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takehito Ujihara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ryosuke Ando National Institute for Land and Infrastructure Management, Ministry of Land, Infrastructure Transport and Tourism Seiji Hashimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University In Japan, unlike in many other countries, urbanization has progressed while original rural road structures have been retained, leading to distinctive urban sprawl areas with intermingling residential lots and farmland. Currently, much of Japan’s urban areas consist of urban sprawl areas, posing considerable challenges for infrastructure development. However, for such urban sprawl areas in Japan, it is difficult to say that methods have been established to identify their spatial distribution based on quantitative evaluation. Therefore, for this study, we used machine learning to investigate a system that extracts sprawling urban areas from aerial photographs divided into meshes. In the system’s design, we prioritized precision to ensure the reliable detection of urban sprawl areas. Consequently, the accuracy of identifying sprawl areas achieved precision of 0.81, recall of 0.63, and an F-score of 0.71. Examination of the classification results of sprawl areas revealed that most misclassifications occurred near class boundaries. By contrast, areas with particularly high levels of urban sprawl showed few misclassifications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals 17 30 EN Hideki Yano Department of Nursing, Faculty of Human Health Sciences, Niimi University Yoko Takahata Graduate School of Health Sciences, Okayama University Takeshi Yamaguchi Faculty of Nursing, Shikoku University Shinya Saito Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/70069 This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scale’s construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior 9 16 EN Kentaro Sugahara Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Yorimasa Yamamoto Innoshima General Hospital Original Article 10.18926/AMO/70068 Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 Perioperative Multidisciplinary Intervention Led to Complete Minimally Invasive Transthoracic Esophagectomy for a Patient With Severe Lung Dysfunction: A Case Report e97931 EN Makoto Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Risk factors for postoperative pneumonia after esophagectomy include smoking, severe lung dysfunction, and sarcopenia. Heavy smokers often have chronic obstructive pulmonary disease (COPD), which is associated with poor physical activity and low muscle strength. Sarcopenia is also associated with decreased physical function and malnutrition. These factors lead to a close relationship between COPD and sarcopenia. This report describes the case of a 74-year-old man who presented with dysphagia and was diagnosed with advanced esophageal cancer with lymph node metastasis. Preoperative respiratory function testing showed a forced expiratory volume in one second (FEV1) of 0.76 L because of his past smoking and COPD. Multidisciplinary intervention was started, along with neoadjuvant chemotherapy. Preoperative management improved his physical function. Robot-assisted thoracoscopic subtotal esophagectomy with the patient in the prone position was performed with curative resection and no severe postoperative complications. The perioperative multidisciplinary intervention improved physical functions and enabled safe robot-assisted thoracoscopic esophagectomy for the patient with severe lung dysfunction in the prone position. This case highlights that not only respiratory status but also physical parameters should be taken into account when considering whether a patient can tolerate surgery safely. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Report e70066 EN Masashi Hashimoto 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 Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 1 2025 Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING 10 EN Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Katayama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunya Hanzawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. 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.

Springer Science and Business Media LLC Acta Medica Okayama 0312-5963 64 12 2025 Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach 1811 1825 EN Walaa Yousef Bassyouni Mahdy Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Joji Department of Pharmacy, Kobe University Hospital Mari Hashimoto Department of Pharmacy, Kobe University Hospital Ruka Nakasone Department of Pediatrics, Graduate School of Medicine, Kobe University Kazumichi Fujioka Department of Pediatrics, Graduate School of Medicine, Kobe University Kotaro Itohara Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Ikuko Yano Department of Pharmacy, Kobe University Hospital Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.<br> Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.<br> Methods A PBPK model was developed and validated against the observed values in the literature. The model’s predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.<br> Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.<br> Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. 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 A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS 1720 EN Ryoichi Nakamura Department of Neurology, Aichi Medical University School of Medicine Genki Tohnai Division of ALS Research, Aichi Medical University School of Medicine Naoki Atsuta Department of Neurology, Aichi Medical University School of Medicine Yumi Matsuda Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Satoru Morimoto Keio University Regenerative Medicine Research Center, Kawasaki Daisuke Ito Department of Neurology, Nagoya University Graduate School of Medicine Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Mitsuya Morita Division of Neurology, Department of Internal Medicine, Jichi Medical University Ikuko Iwata Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Tomoko Nakazato Department of Neurology, Juntendo University School of Medicine Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine Takehisa Hirayama Department of Neurology, Toho University Faculty of Medicine Osamu Kano Department of Neurology, Toho University Faculty of Medicine Asako Tamura Department of Neurology, Mie University Graduate School of Medicine Naoki Suzuki Department of Neurology, Tohoku University Graduate School of Medicine Masashi Aoki Department of Neurology, Tohoku University Graduate School of Medicine Kazumoto Shibuya Department of Neurology, Graduate School of Medicine, Chiba University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Masaya Oda Department of Neurology, Vihara Hananosato Hospital Rina Hashimoto Department of Neurology, NHO Higashinagoya National Hospital Ikuko Aiba Department of Neurology, NHO Higashinagoya National Hospital Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Bokuda Department of Neurology, Tokyo Metropolitan Neurological Hospital Toshio Shimizu Department of Neurology, Tokyo Metropolitan Neurological Hospital Yoshio Ikeda Department of Neurology, Gunma University Graduate School of Medicine Kazuko Hasegawa Division of Neurology, NHO Sagamihara National Hospital Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Takanori Yokota Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo Kazuaki Kanai Department of Neurology, Fukushima Medical University School of Medicine Yu-ichi Noto Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Ryuji Kaji Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Hirohisa Watanabe Department of Neurology, Fujita Health University Tomoko Konishi Division of ALS Research, Aichi Medical University School of Medicine Mikiko Hasegawa Division of ALS Research, Aichi Medical University School of Medicine Hozuki Fukaya Division of ALS Research, Aichi Medical University School of Medicine Jun-ichi Niwa Department of Neurology, Aichi Medical University School of Medicine Manabu Doyu Department of Neurology, Aichi Medical University School of Medicine Yohei Okada Department of Neurology, Aichi Medical University School of Medicine Shiho Nakamura Keio University Regenerative Medicine Research Center, Kawasaki Fumiko Ozawa Keio University Regenerative Medicine Research Center, Kawasaki Hideyuki Okano Keio University Regenerative Medicine Research Center, Kawasaki Masahiro Nakatochi Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Gen Sobue Division of ALS Research, Aichi Medical University School of Medicine Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10−9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Perioperative Team Management Was Beneficially Associated with Prolonged Postoperative Hospital Stays after Long Lower-Abdominal Surgeries 445 449 EN Junya Matsumi Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Original Article 10.18926/AMO/69847 Our hospital began a PERIO program (perioperative patient management by a multi-disciplinary team from multiple departments) in 2016 to improve patient outcomes. We retrospectively analyzed the clinical effects of the PERIO program regarding the postoperative hospital stay (PHS) in the patients aged ≥ 18 years who underwent long lower-abdominal surgery at our hospital during the period April 2019 to March 2023. We excluded the cases of patients whose general anesthesia use was < 8 h, those for whom another surgery was performed simultaneously at another site, and emergency surgeries. The outcome was prolonged PHS, defined as exceeding the scheduled number of days specified in the patient’s clinical pathway. Among the 480 patients, prolonged PHS was observed for 270 patients (56.3%). In a multivariate logistic regression using advanced age, sex, high-risk general state, surgery requiring colon resection, serious adverse events (SAEs), and PERIO use, the following were associated with prolonged PHS: advance age (odds ratio [OR] 4.91, 95% confidence interval [CI]: 2.68-8.99, p=0.01), surgery requiring colon resection (OR 4.91, 95%CI: 2.68-8.99, p<0.001), SAE (OR 18.7, 95%CI: 7.22-48.2, p<0.001), and PERIO (OR 0.25, 95%CI: 0.13-0.47, p<0.001). The use of the PERIO program was thus beneficially associated with PHS after long lower-abdominal surgery. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2189-7948 26 4 2025 Video review by utilizing asynchronous video communication platform 375 378 EN Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiko Mitsuda Kato & Namiki-dori Hospital Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Kato Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mano Soshi BonBon, Inc Masaya Higuchi Harvard Medical School Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadayuki Hashimoto Department of Emergency Medicine, Brigham and Women's Hospital Background: Video review is widely recognized as an effective method for teaching communication; however, it can increase educators' workload and learners' stress.<br> Methods: We utilized Tsucom, an online platform developed by BonBon, Inc., which enables asynchronous video communication instead of traditional styles. An 11-min and 42-s consultation video from a fifth-year resident was uploaded, and 10 physicians provided 30 text-based feedback.<br> Results: In this pilot survey, the utility and ease of use were rated 4.4 and 4.1 out of 5, respectively.<br> Conclusions: While asynchronous online video reviews provided flexibility and greater participation, challenges remain, and further trials and evaluations were deemed necessary. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0305-182X 2025 Is Pain Intensity Related to Psychosocial Factors in Chronic Non‐Nociceptive Orofacial Pain Patients? EN Akiko Kawase Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Fumika Hashimoto Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Midori Inoue Department of Dental Anesthesiology, Okayama University Hospital Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Aki Kawauchi Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Shigeru Maeda Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In order to understand the psychological aspects of chronic pain, it is important to consider the relationships between pain and psychosocial factors in patients with chronic pain. While psychosocial factors are known to affect pain intensity in temporomandibular disorders, few studies have evaluated them in patients with other types of chronic orofacial pain.<br> Objective: The purpose of the present study was to evaluate the relationships between pain intensity and patient characteristics, diagnostic categories and psychosocial factors in chronic non-nociceptive orofacial pain patients.<br> Methods: In a retrospective, cross-sectional study, we collected information from the medical records of 123 patients with chronic non-nociceptive orofacial pain. Pain intensity was measured using the Brief Pain Inventory (BPI) total score. Analysis of the correlations among the variables revealed several strong correlations. Principal component analysis identified two components: the psychological distress and self-efficacy/quality of life (QOL) components. Multiple linear regression analyses of the overall study population and each ICOP pain category were also performed.<br> Results: In the overall sample, higher BPI scores were significantly associated with a greater psychological distress component and lower self-efficacy/QOL component. The pain category was not a significant predictor of the BPI score. In the subgroup analyses, both components were significant predictors of the BPI score in myofascial orofacial pain; whereas, only the self-efficacy/QOL component was in idiopathic orofacial pain.<br> Conclusion: The results indicated that pain intensity in chronic non-nociceptive orofacial pain is related to the self-efficacy/QOL psychosocial factor component. These findings suggest that assessing psychosocial factors may be clinically important for the diagnosis and treatment of chronic orofacial pain. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0929-1903 2025 p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis EN Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kajiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoyuki Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara 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 Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy 38590 EN Chiaki Yagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Kadowaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Yoshida Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masaki Sakamoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Hamada Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoma Sugimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Ohtani Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kumon Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 32 11 2025 Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study 1677 1685 EN Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Lan Inoki Department of Urology, Kindai University Faculty of Medicine Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Yosuke Hirasawa Department of Urology, Tokyo Medical University Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takeshi Hashimoto Department of Urology, Tokyo Medical University Kazumasa Komura Department of Urology, Osaka Medical and Pharmaceutical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Yoshio Ohno Department of Urology, Tokyo Medical University Ryoichi Shiroki Department of Urology, Fujita-Health University School of Medicine Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy.<br> Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment.<br> Results: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio.<br> Conclusions: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study 27684 EN Hiroyuki Tominaga Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hirofumi Shimada Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hiromi Sasaki Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Noboru Taniguchi Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medical University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medical University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Kousei Miura Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Eiki Shirasawa Department of Orthopaedic Surgery, Kitasato University School of Medicine Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Atsushi Kimura Department of Orthopaedics, Jichi Medical University Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hiroshi Moridaira Department of Orthopaedic Surgery, Dokkyo Medical University Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Shuji Watanabe Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Matsumoto Department of Orthopaedic Surgery, Nihon University School of Medicine Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Hidenori Suzuki Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University The usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1752-8054 18 10 2025 Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study e70318 EN Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Takehiro Kawashiri Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Keisuke Mine Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Noriko Hida Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University Kenji Momo Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University Masanobu Uchiyama Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Mami Uchida Department of Pharmacy, Fukuoka University Hospital Mamoru Tanaka Division of Pharmacy, Ehime University Hospital Noriaki Hidaka Division of Pharmacy, Ehime University Hospital Hideki Yasui Center for Clinical Research, Hamamatsu University Hospital Masahiro Ueda Faculty of Pharmaceutical Sciences, Setsunan University Ryohei Fujii Department of Pharmacy, Kansai Medical University Hospital Misaki Hashimoto Department of Pharmacy, Kansai Medical University Hospital Yasutaka Sakamoto Department of Pharmacy, Yokohama City University Hospital Kana Uyama Department of Pharmacy, Yokohama City University Hospital Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Yuki Hanai Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University Ayaka Tsuboya Department of Pharmacy, Kawasaki Municipal Tama Hospital Keisuke Suzuki Innovation Center for Translational Research, National Center for Geriatrics and Gerontology Naoya Kamiyama Asahikawa Medical University Hospital Hiromi Hagiwara Nagoya City University Hospital Naoto Okada Pharmacy Department, Yamaguchi University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2376-7839 11 5 2025 Vanishing White Matter Disease With EIF2B2 c.254T >A Variant e200293 EN Toshiyuki Kakumoto Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Ryo Tokimura Department of Neurology, Graduate School of Medicine, The University of Tokyo Yoko Tsuboyama Department of Neurology, Graduate School of Medicine, The University of Tokyo Yasufumi Hayashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Atsushi Iwata Department of Neurology, Graduate School of Medicine, The University of Tokyo Meiko Hashimoto Maeda Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Shimizu Department of Neurology, Graduate School of Medicine, The University of Tokyo Wataru Gonoi Department of Radiology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Objectives<br> Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.<br> Methods<br> We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant.<br> Results<br> A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance.<br> Discussion<br> This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1367-2223 28 1 2024 Can online interactions reduce loneliness in young adults during university closures in Japan? The directed acyclic graphs approach e12658 EN Kohei Kambara Doshisha University Akihiro Toya Hiroshima University Sumin Lee Hiroshima University Haruka Shimizu Nishikyushu Univ. Junior College Kazuaki Abe Hiroshima University Jun Shigematsu Toyama University Qingyuan Zhang Hiroshima University Natsuki Abe Hiroshima Bunkyo University Ryo Hayase Chubu University Nobuhito Abe Kyoto University Ryusuke Nakai Kyoto University Shuntaro Aoki Fukushima Medical University Kohei Asano Kyoto University Ryosuke Asano Kurume University Makoto Fujimura Fukuoka Jo Gakuin University Ken’ichiro Fukui Kwassui Women's University Yoshihiro Fukumoto Kansai Medical University Kaichiro Furutani Kansai University Koji Hasegawa Komazawa University Hirofumi Hashimoto Osaka Metropolitan University Mikoto Hashimoto Chukyo Gakuin University Hiroki Hosogoshi Kansai University Hiroshi Ikeda Kyushu University Toshiyuki Ishioka Kobe University Chiharu Ito University of Human Environments Suguru Iwano Fukushima Medical University Masafumi Kamada Shujitsu Junior College Yoshihiro Kanai Tohoku Gakuin University Tomonori Karita Ehime University Yu Kasagi Rissho University Emiko S. Kashima La Trobe University Juri Kato Kanazawa Institute of Technology Yousuke Kawachi Tohoku University Jun‐ichiro Kawahara Hokkaido University Masanori Kimura Graduate School of Business Administration, Kobe University Yugo Kira Kurume University Yuko Kiyonaga (Sakoda) Kyushu Kyoritsu University Hiroshi Kohguchi Ryutsu Keizai University Asuka Komiya Hiroshima University Keita Masui Otemon Gakuin University Akira Midorikawa Chuo University Nobuhiro Mifune Kochi University of Technology Akimine Mizukoshi Asahi University Kengo Nawata Fukuoka University Takashi Nishimura Hiroshima International University Daisuke Nogiwa Seikei University Kenji Ogawa Hokkaido University Junko Okada Prefectural University of Hiroshima Aki Okamoto Okayama University Reiko Okamoto Osaka University Kyoko Sasaki Kanagawa University of Human Services Kosuke Sato Kurume University Hiroshi Shimizu Kwansei Gakuin University Atsushi Sugimura Tokai University Yoko Sugitani Sophia University Hitomi Sugiura Kindai University Kyoko Sumioka Okayama University Bumpei Sunaguchi Graduate School of Business Administration, Kobe University Masataka Takebe Otsuma Women's University Hiroki C. Tanabe Nagoya University Ayumi Tanaka Doshisha University Masanori Tanaka Hokkai‐Gakuen University Junichi Taniguchi Tezukayama University Namiji Tokunaga Ehime Prefectural University of Health Sciences Ryozo Tomita Musashino University Yumiko Ueda Asahi University Tomomi Yamashita Jumonji University Kazuho Yamaura Ritsumeikan University Masao Yogo Doshisha University Kenji Yokotani Tokushima University Ayano Yoshida Tohoku Fukushi University Hiroaki Yoshida Shinshu University Katsue Yoshihara Fukuoka Institute of Technology Junior College Ayumi Yoshikawa Osaka Dental University Faculty of Nursing Kuniaki Yanagisawa Kobe University Ken'ichiro Nakashima Hiroshima University As a countermeasure to the increased loneliness induced by the COVID-19 pandemic-related university closures, universities provided students with online interaction opportunities. However, whether these opportunities contributed to reducing loneliness during the university closures remains unclear, as previous studies have produced contradictory findings. We conducted a nationwide cross-sectional survey. Data were collected on demographics, social environment, social support, interactions, health and loneliness from 4949 students from 60 universities across Japan. We used psychological network and Directed Acyclic Graphs (DAGs) to examine the effect of online interactions on loneliness during university closures during COVID-19. The results showed that the frequency of online interactions with friends did not exert a significant influence on loneliness during university closures. A comparative examination of the DAGs further illuminated that the social environment exhibited fewer pathways for interpersonal interactions and social support during these closure periods. The psychosocial pathways influencing young adults' loneliness show variations contingent on the university's closure status. Notably, the impact of heightened online interactions with friends on loneliness appears to be less pronounced among young adults in the context of university closure. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2731-0590 4 9 2025 Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC–CXCL1–CXCR2 axis 1135 1151 EN Jin Komuro Department of Cardiology, Keio University School of Medicine Hisayuki Hashimoto Department of Cardiology, Keio University School of Medicine Toshiomi Katsuki Department of Cardiology, Keio University School of Medicine Dai Kusumoto Department of Cardiology, Keio University School of Medicine Manami Katoh Department of Frontier Cardiovascular Science, Graduate School of Medicine Toshiyuki Ko Department of Frontier Cardiovascular Science, Graduate School of Medicine Masamichi Ito Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Mikako Katagiri Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Masayuki Kubota Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Shintaro Yamada Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Takahiro Nakamura Department of Cardiology, Keio University School of Medicine Yohei Akiba Department of Cardiology, Keio University School of Medicine Thukaa Kouka Department of Cardiology, Keio University School of Medicine Kaoruko Komuro Department of Cardiology, Keio University School of Medicine Mai Kimura Department of Cardiology, Keio University School of Medicine Shogo Ito Department of Cardiology, Keio University School of Medicine Seitaro Nomura Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Issei Komuro Department of Frontier Cardiovascular Science, Graduate School of Medicine Keiichi Fukuda Department of Cardiology, Keio University School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Ieda Department of Cardiology, Keio University School of Medicine Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage. This HF-specific CF population highly expresses the transcription factor Myc. Deleting Myc in CFs improves cardiac function without reducing fibrosis. MYC directly regulates the expression of the chemokine CXCL1, which is elevated in HF-specific CFs and downregulated in Myc-deficient CFs. The CXCL1 receptor, CXCR2, is expressed in cardiomyocytes, and blocking the CXCL1–CXCR2 axis mitigates HF. CXCL1 impairs contractility in neonatal rat and human iPSC-derived cardiomyocytes. Human CFs from failing hearts also express MYC and CXCL1, unlike those from controls. These findings reveal that HF-specific CFs contribute to HF via the MYC–CXCL1–CXCR2 pathway, offering a promising therapeutic target beyond cardiomyocytes. No potential conflict of interest relevant to this article was reported.

Izmir Akademi Dernegi Acta Medica Okayama 2792-0232 5 2 2025 Metaverse Support Groups for LGBTQ+ Youth: An Observational Study on Safety, Self-Expression, and Early Intervention 156 167 EN Joe Hasei Okayama University Yosuke Matsumoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceu-tical Sciences, Okayama University This study explored whether metaverse-based support groups could address social isolation and suicide risks among LGBTQ+ youths by providing enhanced anonymity, avatar-based self-expression, and improved accessibility. Over one year, 53 individuals aged 14–23 participated in regular online sessions facilitated via the "cluster" metaverse platform by a non-profit LGBTQ+ organization. Each 90-minute session included voice and text-based interactions within a specially designed single-floor virtual space featuring conversation areas and a designated "safe area" for emotional regulation. Post-session questionnaires (5-point Likert scales) captured demographics, avatar preferences, self-confidence, and perceived safety, self-expression, and accessibility; responses were analyzed with Pearson's chi-squared test and Mann–Whitney U tests (α=0.05). Results indicated that 79.2% of participants selected avatars aligned with their gender identity, reporting high satisfaction (mean = 4.10/5) and minimal discomfort (mean = 1.79/5). Social confidence was significantly higher in the metaverse compared with real-world settings (p<0.001), particularly among those with lower real-world confidence, who exhibited an average gain of 2.08 points. Approximately half of all first-time participants were aged 16 years or younger, which suggested the platform’s value for early intervention. Additionally, the metaverse environment was rated significantly higher in safety/privacy (3.94/5), self-expression (4.02/5), and accessibility (4.21/5) compared with the real-world baseline, and 73.6% reported they felt more accepted virtually. However, some participants who had high confidence offline experienced mild adaptation challenges (mean decrease of 0.58 points), which highlighted that metaverse-based support may be more effective as a complement to in-person services rather than a replacement. Overall, these findings demonstrate that metaverse-based support groups can reduce psychological barriers for LGBTQ+ youth by facilitating safe and affirming virtual environments. The metaverse may help alleviate emotional distress and prevent further severe outcomes, such as suicidal ideation by providing early intervention, especially for adolescents unable to access conventional in-person services. Further research should examine its integration with existing clinical, community, and educational resources to ensure comprehensive, long-term support. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8049 37 1 2025 Fan-Shaped Pneumatic Soft Actuator that Can Operate Bending Motion for Ankle-Joint Rehabilitation Device 43 53 EN So Shimooka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirosato Yokoya Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Shun Shiomi Department of Rehabilitation Medicine, Okayama University Hospital Takenori Uehara Department of Orthopaedic Surgery, NHO Okayama Medical Center Takahiro Hirayama Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsushi Kamegawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University Nowadays, owing to declining birthrates and an aging population, patients and the elderly requiring rehabilitation are not getting enough physical activity. In addressing this issue, devices for rehabilitating them have been researched and developed. However, rehabilitation devices are almost exclusively used for patients who can get up, rather than those who are bedridden. In this study, we aim to develop a rehabilitation device that can provide passive exercise for bedridden patients. The ankle joint was selected as the target joint because the patients who have undergone surgery for cerebrovascular disease remain bedridden, and early recovery in the acute stage is highly desirable. We proposed and tested a fan-shaped pneumatic soft actuator (FPSA) that can expand and bend stably at angles when supply pressure is applied as an actuator for a rehabilitation device to encourage patient exercise. However, the previous FPSA’s movement deviates from the arch of the foot owing to increased supply pressure. In the ideal case, FPSA should push the arch of the foot in an arc motion. This study proposes and tests the FPSA that can operate a bending motion to provide passive exercise to the ankle joint using tensile springs and a winding mechanism powered by a servo motor. The proposed FPSA has a significant advantage of exhibiting no hysteresis in its pressure-displacement characteristics. The configuration and static analytical model of the improved FPSA are described. No potential conflict of interest relevant to this article was reported.

American Physiological Society Acta Medica Okayama 1040-0605 329 1 2025 Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension L183 L196 EN Satomi Imakiire Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keiji Kimuro Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keimei Yoshida Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kohei Masaki Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Ryo Izumi Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Misaki Imabayashi Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Takanori Watanabe Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Tomohito Ishikawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kazuya Hosokawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Shouji Matsushima Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Toru Hashimoto Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keisuke Shinohara Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Shunsuke Katsuki Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Tetsuya Matoba Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Katsuya Hirano Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Hiroyuki Tsutsui Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kohtaro Abe Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-κB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-κB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH.<br> NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-κB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Mimicking Contralateral Pneumothorax during Thoracoscopic Bullectomy Associated with Intraoperative Hyperinflation of a Large Bulla in an Obese Patient 311 315 EN Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Yutaka Hirano Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Case Report 10.18926/AMO/69159 A 55-year-old obese Japanese male with left pneumothorax presented to our hospital. Bilateral pulmonary emphysema was confirmed. Persistent air leakage was observed, and a thoracoscopic bullectomy was performed. Although the thoracoscopic bullectomy was completed uneventfully, pre-extubation chest X-ray imaging indicated hyper-lucency occupying the right upper part of the thoracic cavity, suggesting right-sided pneumothorax. CT imaging indicated a right-upper-lobe expanded bulla. Extubation was performed, and the hyperinflated bulla gradually deflated. Careful management of bulla expansion and respiratory status may be necessary for patients with obesity and large bullae, especially in one-lung ventilation cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Outcome of Decompression Surgery Following Rapid Neurological Deterioration in Patients with Spinal Cord Injury Without Radiographic Evidence of Trauma (SCIWORET) 261 267 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Miyake Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69151 Cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) increase the likelihood of spinal cord injury without radiographic evidence of trauma (SCIWORET). Opinions regarding the optimal timing for surgery in such cases vary, however. We retrospectively investigated the demographics and outcomes of patients with SCIWORET who underwent surgery shortly after experiencing rapid neurological deterioration, and we matched patients who underwent standby surgery for CSM or OPLL. Although the optimal timing of surgery for SCIWORET remains unclear, our findings suggest that early stage surgery for SCIWORET may yield favorable neurological improvements. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Study of Periprosthetic Femoral Stem Fractures in Hip Arthroplasty for Femoral Neck Fracture 253 259 EN Yoshiaki Miyake Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Toru Takagi Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Taizo Konishiike Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Original Article 10.18926/AMO/69150 This study investigated the risk factors for bone fragility and perioperative periprosthetic femoral stem fractures in patients undergoing hip arthroplasty for femoral neck fractures. The records of 215 patients (42 male, 173 female; mean age, 84.4 years) were analyzed to assess correlations among periprosthetic fracture rates and sex, age, body mass index (BMI), Dorr classification, femoral stem fixation type (cemented/cementless), and bone mineral density (BMD) of the contralateral proximal femur. The overall prevalence of perioperative periprosthetic fractures was 4.7%. All patients with periprosthetic fractures were female, and all but one were ≥ 80 years of age. Fracture rates were higher in patients with lower BMI, although this difference was not significant. The fracture rates were 0%, 4.7%, and 7.9% for Dorr types A, B, and C, respectively, and 0% and 5.3% for patients who received cemented and cementless stems, respectively. The findings indicated that female patients, those of advanced age, those with lower BMI, and those with Dorr type C had lower BMDs. Although BMD was significantly lower in patients who received cemented stems compared to those who received cementless stems, no fractures were observed in the former group, suggesting that the use of cemented stems is safe for this high-risk population. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 24 2024 A Preliminary Survey of Rheumatologists on the Management of Late-onset Rheumatoid Arthritis in Japan 3299 3306 EN Satoshi Takanashi Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Yuko Kaneko Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Yutaka Kawahito Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takashi Kida Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takahiko Sugihara Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine Toshihisa Kojima National Hospital Organization Nagoya Medical Center, Orthopaedic Surgery and Rheumatology Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Michinori Ishitoku Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Shintaro Hirata Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Motomu Hashimoto Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine Toshihiko Hidaka Miyazaki-Zenjinkai Hospital Asami Abe Department of Rheumatology, Niigata Rheumatic Center Hajime Ishikawa Department of Rheumatology, Niigata Rheumatic Center Hiromu Ito Kurashiki Central Hospital Mitsumasa Kishimoto Department of Nephrology and Rheumatology, Kyorin University School of Medicine Kazuo Matsui Department of Rheumatology, Teine Keijinkai Hospital Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Isao Matsushita Department of Rehabilitation Medicine, Kanazawa Medical University Akira Onishi Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University Akio Morinobu Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Keiichiro Nishida Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuji Asai Department of Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine Eiichi Tanaka Division of Rheumatology, Department of Internal Medicine, Tokyo Women&apos;s Medical University School of Medicine Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, Tokyo Women&apos;s Medical University School of Medicine Masayo Kojima Department of Public Health, Nagoya City University Graduate School of Medical Sciences Objective We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice.<br> Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses.<br> Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation.<br> Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-0105 10 1 2025 Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine 158 EN Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanto Suemori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naohiro Okada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kajiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Inoue Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoyuki Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Hospital Yasuo Urata Oncolys BioPharma, Inc Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Survival days of patients with metastatic spinal tumors of lung cancer requiring surgery: a prospective multicenter study 24117 EN Takuya Takahashi Department of Orthopedic Surgery, Institute of Science Tokyo Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Satoshi Kato Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kanazawa University Hiroyuki Tominaga Department of Orthopedic Surgery Graduate School of Medical and Dental Sciences, Kagoshima University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Masayuki Ishihara Department of Orthopaedic surgery, Kansai Medical University Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Toru Funayama Department of Orthopaedic Surgery Institute of Medicine, University of Tsukuba Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Toshitaka Yoshii Department of Orthopedic Surgery, Institute of Science Tokyo Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Surgery for metastatic spinal tumors has improved postoperative activities of daily living. A few studies reported on prognostic factors assessed in large multicenter prospective studies for metastatic spinal tumors of lung cancer origin. This study aimed to determine preoperative prognostic factors in patients undergoing surgery for metastatic spinal tumors associated with lung cancer. This prospective registry study included 74 patients diagnosed and operated with metastatic spine tumors derived from lung cancer in 39 high-volume cancer centers. We examined the postoperative survival period and the preoperative factors related to postoperative survival time. We conducted univariate and multivariate Cox regression analyses to determine preoperative prognostic factors. The mean postoperative survival period was 343 days. Multivariate Cox regression analysis revealed a higher feeding score of vitality index, indications for molecularly targeted therapy, and a higher mobility score of Barthel index as independent factors associated with postoperative survival time in metastatic spinal tumors derived from lung cancer. Patients with indications for molecular-targeted therapy and good vitality exhibited longer survival. These results may help in surgical selection for patients with metastatic spinal tumors derived from lung cancer. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2192-5682 15 4 2024 Effects of Palliative Surgical Treatment for Spinal Metastases on the Patient’s Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study 2286 2299 EN Naoki Segi Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Sadayuki Ito Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Jun Ouchida Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Yuki Shiratani Department of Orthopaedic Surgery, Chiba University Hospital Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Hiroyuki Tominaga Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medial University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medial University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Takashi Hirai Department of Orthopedic Surgery, Tokyo Medical and Dental University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kota Watanabe Department of Orthopaedic Surgery, Keio University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Chiba University Hospital Study Design: Prospective multicenter study.<br> Objectives: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments.<br> Methods: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper–middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared.<br> Results: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 ± 0.291; thoracic, 0.321 ± 0.292; and TL/L/S, 0.376 ± 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 ± 0.233; thoracic, 0.513 ± 0.252; and TL/L/S, 0.624 ± 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 ± 25.8; thoracic, 54.7 ± 24.5; and TL/L/S, 61.7 ± 21.9).<br> Conclusions: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1550-4131 37 2 2025 Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring 395 412.e6 EN Na Yao Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Kenichiro Kinouchi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Manami Katoh Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Kousha Changizi Ashtiani Department of Computer Science, University of California Sherif Abdelkarim Department of Computer Science, University of California Hiroyuki Morimoto Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences Takuto Torimitsu Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Takahide Kozuma Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Akihide Iwahara Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Shotaro Kosugi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Jin Komuro Department of Cardiology, Keio University School of Medicine Kyosuke Kato Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Shun Tonomura Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Toshifumi Nakamura Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Arata Itoh Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Shintaro Yamaguchi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Jun Yoshino Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Junichiro Irie Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Hisayuki Hashimoto Department of Cardiology, Keio University School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University Akiko Satoh Department of Integrative Physiology, Institute of Development, Aging and Cancer, Tohoku University Yohei Mikami Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine Shusaku Uchida Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences Takatoshi Ueki Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences Seitaro Nomura Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Pierre Baldi Department of Computer Science, University of California Kaori Hayashi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Hiroshi Itoh Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy 27163 EN Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Kazumasa Komura Department of Urology, Osaka Medical and Pharmaceutical University Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Kiyoshi Takahara Department of Urology, Fujita Health University School of Medicine Takuhisa Nukaya Department of Urology, Fujita Health University School of Medicine Lan Inoki Department of Urology, Kindai University Faculty of Medicine Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Takeshi Hashimoto Department of Urology, Tokyo Medical University Yosuke Hirasawa Department of Urology, Tokyo Medical University Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuma Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyohei Kurose Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Kimura Department of Urology, The Jikei University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Ryoichi Shiroki Department of Urology, Fujita Health University School of Medicine Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Yoshio Ohno Department of Urology, Tokyo Medical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23–4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39–5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Development of a unique tissue-engineered in vitro vascular model with endothelial layer-inverted vascular tissue structure using a cell self-aggregation technique EN Shingo HASHIMOTO 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 Promising Effectiveness of Combined Chemotherapy and Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Real-World Prospective Observational Study (CS-Lung-003) 167 176 EN Nobuhiro Kanaji Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University Kazuya Nishii Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Yukari Tsubata Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Mika Nakao Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Takae Okuno Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Sachi Okawa Department of Allergy and Respiratory Medicine, Okayama University Hospital Kenji Takata Department of Allergy and Respiratory Medicine, Okayama University Hospital Masahiro Kodani Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University Masahiro Yamasaki Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Kazunori Fujitaka Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Tetsuya Kubota Department of Respiratory Medicine and Allergology, Kochi University Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Naoki Watanabe Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital CS-Lung-003 Investigator Original Article 10.18926/AMO/68724 This prospective observational study investigated the clinical status of patients with advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy+an immune checkpoint inhibitor (chemo + IO) as first-line treatment in a real-world setting. The cases of 98 patients treated with chemo + IO were prospectively collected and analyzed for effectiveness and safety. The response rate to chemo + IO was 46.9%, and the disease control rate was 76.5%. The median progression-free survival and overall survival (OS) in the total population were 5.2 and 22.3 months, respectively. The patients positive for PD-L1 (≥ 1%) showed significantly longer OS than the negative group (<1%) (median 26.7 vs. 18.7 months, p=0.04). Pre-existing interstitial lung disease (ILD) was associated with shorter OS than the absence of ILD (median 9.0 vs. 22.6 months, p<0.01). Immunerelated adverse events (irAEs) were observed in 28 patients (28.6%). The most frequent irAE was ILD (n=11); Grade 1 (n=1 patient), G2 (n=5), G3 (n=4), and only a single patient with a G5 irAE. In this CS-Lung-003 study, first-line chemo + IO in a real-world setting showed good effectiveness, comparable to that observed in international clinical trials. In real-world practice, chemo + IO is a promising and steadfast strategy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring 139 144 EN Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Hospital Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Hospital Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Hospital Yohei Mizusawa Department of Gastroenterological Surgery, Okayama University Hospital Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Hospital Yuhei Kondo Department of Gastroenterological Surgery, Okayama University Hospital Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Hospital Yukinori Tanoue Department of Gastroenterological Surgery, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Hospital Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Case Report 10.18926/AMO/68654 In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Local-structure insight into the improved superconducting properties of Pb-substituted La(O, F)BiS2: a photoelectron holography study 8366 EN Yajun Li Graduate School of Natural Science and Technology, Okayama University Yusuke Hashimoto Nara Institute of Science and Technology (NAIST) Noriyuki Kataoka Graduate School of Natural Science and Technology, Okayama University Zexu Sun Nara Institute of Science and Technology (NAIST) Sota Kawamura Nara Institute of Science and Technology (NAIST) Hiroto Tomita Nara Institute of Science and Technology (NAIST) Taro Setoguchi Graduate School of Natural Science and Technology, Okayama University Soichiro Takeuchi Nara Institute of Science and Technology (NAIST) Shunjo Koga Nara Institute of Science and Technology (NAIST) Kohei Yamagami Japan Synchrotron Radiation Research Institute (JASRI) Yoshinori Kotani Japan Synchrotron Radiation Research Institute (JASRI) Satoshi Demura Department of Physics, College of Science and Technology(CST), Nihon University Kanako Noguchi Tokyo University of Science Hideaki Sakata Tokyo University of Science Tomohiro Matsushita Nara Institute of Science and Technology (NAIST) Takanori Wakita Graduate School of Natural Science and Technology, Okayama University Yuji Muraoka Graduate School of Natural Science and Technology, Okayama University Takayoshi Yokoya Graduate School of Natural Science and Technology, Okayama University Pb-substituted La(O, F)BiS2 (Pb-LaOFBiS2) exhibits improved superconducting properties and a resistivity anomaly around 100 K that is attributed to a structural transition. We have performed temperature(T)-dependent photoelectron holography (PEH) to study dopant incorporation sites and the local structure change across the anomaly. The PEH study of Pb-LaOFBiS2 provided evidence for the dominant incorporation sites of Pb and F: Pb atoms are incorporated into the Bi sites and F atoms are incorporated into the O site. No remarkable difference in the local structures around Pb and Bi atoms was observed. Across the temperature of the resistivity anomaly (T*), photoelectron holograms of Bi 4f changed. Comparisons of holograms with those of non-substituted LaOFBiS2 sample, as well as simulated holograms, suggested that (1), above T*, the tetragonal structure of Pb-LaOFBiS2 is different from the tetragonal structure of LaOFBiS2 and (2), below T*, the tetragonal structure still remains in Pb-LaOFBiS2. We discuss a possible origin of the difference in the structure above T* and the implication of the result below T*, which are necessary ingredients to understand the physical properties of Pb-LaOFBiS2. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-445X 14 2 2025 Interchangeability of Cross-Platform Orthophotographic and LiDAR Data in DeepLabV3+-Based Land Cover Classification Method 217 EN Shijun Pan Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University Takashi Kojima TOKEN C. E. E. Consultants Co., Ltd. Yutaro Hashimoto Graduate School of Environmental and Life Science, Okayama University Riverine environmental information includes important data to collect, and the data collection still requires personnel's field surveys. These on-site tasks still face significant limitations (i.e., hard or danger to entry). In recent years, as one of the efficient approaches for data collection, air-vehicle-based Light Detection and Ranging technologies have already been applied in global environmental research, i.e., land cover classification (LCC) or environmental monitoring. For this study, the authors specifically focused on seven types of LCC (i.e., bamboo, tree, grass, bare ground, water, road, and clutter) that can be parameterized for flood simulation. A validated airborne LiDAR bathymetry system (ALB) and a UAV-borne green LiDAR System (GLS) were applied in this study for cross-platform analysis of LCC. Furthermore, LiDAR data were visualized using high-contrast color scales to improve the accuracy of land cover classification methods through image fusion techniques. If high-resolution aerial imagery is available, then it must be downscaled to match the resolution of low-resolution point clouds. Cross-platform data interchangeability was assessed by comparing the interchangeability, which measures the absolute difference in overall accuracy (OA) or macro-F1 by comparing the cross-platform interchangeability. It is noteworthy that relying solely on aerial photographs is inadequate for achieving precise labeling, particularly under limited sunlight conditions that can lead to misclassification. In such cases, LiDAR plays a crucial role in facilitating target recognition. All the approaches (i.e., low-resolution digital imagery, LiDAR-derived imagery and image fusion) present results of over 0.65 OA and of around 0.6 macro-F1. The authors found that the vegetation (bamboo, tree, grass) and road species have comparatively better performance compared with clutter and bare ground species. Given the stated conditions, differences in the species derived from different years (ALB from year 2017 and GLS from year 2020) are the main reason. Because the identification of clutter species includes all the items except for the relative species in this research, RGB-based features of the clutter species cannot be substituted easily because of the 3-year gap compared with other species. Derived from on-site reconstruction, the bare ground species also has a further color change between ALB and GLS that leads to decreased interchangeability. In the case of individual species, without considering seasons and platforms, image fusion can classify bamboo and trees with higher F1 scores compared to low-resolution digital imagery and LiDAR-derived imagery, which has especially proved the cross-platform interchangeability in the high vegetation types. In recent years, high-resolution photography (UAV), high-precision LiDAR measurement (ALB, GLS), and satellite imagery have been used. LiDAR measurement equipment is expensive, and measurement opportunities are limited. Based on this, it would be desirable if ALB and GLS could be continuously classified by Artificial Intelligence, and in this study, the authors investigated such data interchangeability. A unique and crucial aspect of this study is exploring the interchangeability of land cover classification models across different LiDAR platforms. 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.<br> 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.<br> 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.<br> 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.

Elsevier Acta Medica Okayama 2210-2612 126 2025 Laparoscopic resection for oesophageal duplication cyst: A case report 110572 EN Tomohiro Hamazaki 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 Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Oesophageal duplication cyst is a congenital malformation and rare tumour, clinically manifesting as dysphagia, epigastric pain, or respiratory distress. Duplicate cysts associated with abscess formation or mediastinal penetration and malignancies have been reported, necessitating surgical resection. <br> Presentation of case: A 55-year-old woman had chest discomfort for 1 year. Preoperative imaging, including computed tomography (CT), upper gastrointestinal endoscopy, and endoscopic ultrasound, revealed a tumour extending from the anterior wall to the lesser curvature of the near the oesophagogastric junction (OGJ) and a suspected mural nodule within the tumour. Contrast-enhanced CT revealed a cystic nodule on the wall of the lesser curvature of the OGJ, with an unclear boundary between the cystic nodule and the oesophageal wall. Magnetic resonance imaging showed an isointense signal on T1-weighted imaging and hyperintensity on T2weighted imaging. Laparoscopic lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed to the confirm mucinous cyst. Pathological findings revealed a cystic lesion in the muscularis propria of the OGJ filled with mucinous components and lined with multilayered columnar epithelial cells. The cyst was diagnosed as a duplicate without malignancy. <br> Discussion: Since the border between the cyst and the oesophageal walls was unclear, and the cyst potentially contained a malignant component, instead of cystectomy, lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed with oesophagogastric anastomosis using the double-flap technique, tailored specifically for OGJ cancer. <br> Conclusions: Oesophageal duplication cysts are rare. Lower oesophagectomy and proximal gastrectomy are selective surgical approaches for cyst duplication at the OGJ. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Traumatic Neuroma Arising from Surgical Trauma during Conversion from Laparoscopic to Open Cholecystectomy 459 464 EN Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, 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 Case Report 10.18926/AMO/67872 Traumatic neuroma is an abnormal proliferation of injured nerves resulting from trauma or surgery. We present a case of traumatic neuroma arising in the cystic duct after cholecystectomy. A 66-year-old man was referred to our department due to a biliary tumor. He had undergone cholecystectomy 20 years prior. Cholangioscopy showed an elevated lesion covered with smooth mucosa. Histological examination revealed normal bile duct mucosa. Although benign disease was suspected, the possibilities of malignant disease could not be excluded. Extrahepatic bile duct resection was planned to include intraoperative rapid-freezing of a biopsy specimen followed by histopathological examination. These intraoperative histology results showed proliferation of nerve and fibrous tissue only, resulting in the diagnosis of traumatic neuroma, so no lymph nodes were removed. To avoid excessive surgical intervention, histopathological examination of an intraoperative rapid-frozen biopsy specimen may be important for diagnosing traumatic neuroma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Partial versus Radical Nephrectomy for Small Renal Cancer: Comparative Propensity Score-Matching Analysis of Cardiovascular Event Risk 429 437 EN Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67868 Although partial nephrectomy (PN) is preferred over radical nephrectomy (RN) for preserving renal function in patients with cT1 renal cancer, its impact on cardiovascular events (CVe) remains controversial. This study aimed to compare PN and RN in regard to the occurrence of CVe, including cerebrovascular events and exacerbation of hypertension (HT). We retrospectively analyzed 418 consecutive patients who underwent PN or RN for cT1 renal cancer. Propensity score-matching analysis was used to adjust for imbalances between patients who underwent PN and RN, leaving 102 patients in each group. The 5-year probability of cumulative CVe incidence was 6% in the PN group and 12% in the RN group (p=0.03), with a median follow-up of 73.5 months. The statistical significance was retained after propensity score matching for patients without preoperative proteinuria (p=0.03). For all CVe including cerebrovascular events and exacerbation of HT analyzed, PN provided a lower probability of occurrence than RN in patients with small renal cancers. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer EN Kazuma IWATA 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 Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus EN Masashi HASHIMOTO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 6 2 2023 Disease and Injury Trends following Heavy Rains in Western Japan in 2018 129 137 EN Chiaki Hashimoto Department of Epidemiology, Graduate School of Medicine, Density and Pharmaceutical Sciences Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Density and Pharmaceutical Sciences Okayama University Kazuharu Murakami Mabi Memorial Hospital Shigeru Suganami Association of Medical Doctors of Asia Introduction: Torrential rains occurred in Okayama in western Japan in July 2018, forcing local residents to evacuate. Few studies have reported early-phase disease and injury trends among patients following torrential rains. Thus, in this study, we assessed the illness and injury trends among patients who visited temporary medical facilities located in the areas affected by the 2018 torrential rains; these facilities opened 10 d after the disaster.<br> Methods: We evaluated the trends among patients who visited a medical clinic located in the area in western Japan affected by heavy rains in 2018. We reviewed medical charts related to 1,301 outpatient visits and conducted descriptive analyses.<br> Results: More than half of the patients were over 60 years old. The patients experienced mild injuries (7.9% of total visits) as well as common diseases such as hypertensive diseases (30%), diabetes mellitus (7.8%), acute upper respiratory infections (5.4%), skin diseases (5.4%), and eye diseases (4.8%). Hypertensive diseases were the main cause of a visit in any week. Eye problems were the second-highest reason for a visit in the first week, but there was a relative decrease from the first to the third week. Additionally, the proportion of injuries and skin diseases increased from the first to the second week, from 7.9% to 11.1% for injuries, and from 3.9% to 6.7% for skin diseases.<br> Conclusions: The types of diseases changed on a weekly basis. Older adults needed medical support for longer than other age groups. Prior preparedness such as earlier deployment of such temporary clinics can help mitigate the damage to the victims. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 74 1 2024 Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity 12 EN Tomoko Ohtani Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 10 1 2024 Gastro-tracheal fistula following esophageal cancer surgery through the retrosternal route: a case report 252 EN Seitaro Nishimura Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Noma Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kawasaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuya Kato Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Naoaki Maeda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Tanabe Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiro Shirakawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Gastro-tracheal fistula is a rare but serious complication after esophageal surgery, often requiring long-term treatment and invasive procedures. Gastro-tracheal fistula usually occurs through the posterior mediastinal route and rarely through the retrosternal route. No previous reports have described gastro-tracheal fistula after retrosternal route reconstruction was cured by conservative treatment.<br> Case presentation A 70-year-old man with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy in the prone position and gastric tube reconstruction through the retrosternal route with neck anastomosis after neoadjuvant chemotherapy. Despite anastomotic leakage on postoperative day 10, his general condition was stable, and he was managed conservatively with antibiotics and gastric tube decompression. On day 29, he presented with high fever and a gastro-tracheal fistula was observed by esophagography. Conservative management was continued because the patient remained stable. On day 48, esophagography showed that the fistula was undetectable. The patient was able to take fluids orally. He progressed well on an oral diet and was transferred to a different hospital.<br> Conclusions A gastro-tracheal fistula, although rare, can occur after retrosternal route reconstruction. When a patient is stable, gastro-tracheal fistula after retrosternal route reconstruction may be cured by conservative treatment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Pediatric Severe Febrile Thrombocytopenia Syndrome: A Case Report and Literature Review 401 405 EN Yusuke Toyota Department of Pediatrics, NHO Iwakuni Clinical Center Kazuhiro Uda Department of Pediatrics, NHO Iwakuni Clinical Center Komei Shirabe Yamaguchi Prefectural Institute of Public Health and Environment Tadashi Moriwake Department of Pediatrics, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/67664 Severe febrile thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease that is endemic in parts of eastern Asia. Few pediatric cases have been reported. We describe a case of SFTS in a seven-year-old girl who presented with prolonged fever and gastrointestinal symptoms. Leukopenia and thrombocytopenia on hematology, and a history of outdoor activity led us to diagnose SFTS, although the patient had no tick bite marks. We also review the literature and discuss the characteristics of pediatric SFTS. Physicians should consider SFTS in the differential diagnosis of fever with thrombocytopenia in children living in endemic areas. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital 371 376 EN Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Miyoshi Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University I Putu Bayu Mayura Department of Clinical Microbiology, Faculty of Medicine, Udayana University Shuma Tsuji Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Original Article 10.18926/AMO/67657 Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control. 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.<br> 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.<br> 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).<br> 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 A Multidisciplinary Approach to Hip Fractures: Evaluating Outcomes on Mortality and Secondary Hip Fractures 237 243 EN Osamu Muraoka Department of Orthopedic Surgery, Niigata Prefectural Tokamachi Hospital Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Tatsuya Kuraishi Department of Orthopedic Surgery, Niigata Prefectural Tokamachi Hospital Makoto Imai Department of Orthopedic Surgery, Niigata Prefectural Tokamachi Hospital Takashi Fukuhara Department of Orthopedic Surgery, Niigata Prefectural Tokamachi Hospital Toshifumi Yoshimine Department of Internal Medicine, Niigata Prefectural Tokamachi Hospital Original Article 10.18926/AMO/67198 Fracture liaison services (FLS) have been introduced in Japan and several other countries to reduce medical complications and secondary fractures. We aimed to evaluate the effects of the implementation of an FLS approach on patient outcomes during hospitalization at our hospital and over a 2-year follow-up post-injury. This retrospective cohort study included patients ≥ 60 years admitted to our hospital for hip fragility fractures between October 1, 2016, and July 31, 2020. Patient groups were defined as those treated before (control group, n=238) and after (FLS group, n=196) establishment of the FLS protocol at our institution. The two groups were compared in terms of time to surgery, length of hospital stay, and the incidence of complications after admission, including secondary hip fracture and mortality rates. The follow-up period was 24 months. FLS focuses on early surgery within 48 h of injury and assessing osteoporosis treatment before injury to guide post-discharge anti-osteoporosis medication. FLS reduced the length of hospital stay (p<0.001) and the prevalence of complications after admission (p<0.001), particularly cardiovascular disease, and it increased adherence to anti-osteoporosis medication. These FLS effects resulted in lower secondary hip fracture and mortality rates at 12 and 24 months post-injury. FLS for fragility hip fractures can improve patient outcomes during hospitalization and over a 2-year follow-up period. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 10 1 2024 Subtotal esophagectomy and concurrent reconstruction with free jejunal flap for primary esophageal cancer after pancreatoduodenectomy 128 EN Kazuya Moriwake 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 Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tasuku Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological 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 Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Pancreatoduodenectomy and subtotal esophagectomy are widely considered the most invasive and difficult surgical procedures in gastrointestinal surgery. Subtotal esophagectomy after pancreatoduodenectomy is expected to be extremely difficult due to complicated anatomical changes, and selecting an appropriate intestinal reconstruction method will also be a difficult task. Therefore, perhaps because the method is considered impossible, there have been few reports of subtotal esophagectomy after pancreatoduodenectomy.<br> Case presentation A 73-year-old man with a history of pancreatoduodenectomy was diagnosed with superficial thoracic esophageal squamous cell carcinoma. Definitive chemoradiation therapy was recommended at another hospital; however, he visited our department to undergo surgery. We performed the robot-assisted thoracoscopic subtotal esophagectomy. There were some difficulties with the reconstruction: the gastric tube could not be used, the reconstruction was long, and the organs reconstructed in the previous surgery had to be preserved. However, the concurrent reconstruction was achieved with the help of a free jejunal flap and vascular reconstruction. All reconstructions from the previous surgery, including the remnant stomach, were preserved via regional abdominal lymph node dissection. After reconstruction, intravenous indocyanine green showed that circulation in the reconstructed intestines was preserved. On postoperative day 1, no recurrent nerve paralysis was observed during laryngoscopy. The patient could start oral intake smoothly 2 weeks after surgery and did not exhibit any postoperative complications related to the reconstruction. The patient was transferred to another hospital on postoperative day 21.<br> Conclusions Owing to the free jejunal flap interposition method, we safely performed one stage subtotal esophagectomy and concurrent reconstruction, preservation of the remnant stomach, and pancreaticobiliary reconstruction in patients with a history of pancreatoduodenectomy. We believe that this method is acceptable and useful for patients undergoing complicated reconstruction. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2210-2612 117 2024 Surgical repair for a parahiatal hernia with an esophageal hiatal hernia: A case report and literature review 109565 EN Yosuke Takahashi 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 Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction and importance: A parahiatal hernia (PH) is a rare diaphragmatic hernia (DH) adjacent to but separated from the esophageal hiatus. The surgical repair for PH needs primary suture closure or complicated hernioplasty and the addition of an anti-reflux procedure. This report describes a case of PH with a symptomatic esophageal hiatal hernia managed using three-dimensional (3D) laparoscopy. <br> Case presentation: A 65-year-old woman with back pain and breathlessness was referred to our hospital for a DH. Computed tomography showed a diaphragmatic defect on the left side of the esophageal hiatus. Upper gastrointestinal endoscopy and 24-hour esophageal impedance-pH monitoring showed a symptomatic esophageal hiatal hernia. Laparoscopic repair for both hernias was performed using 3D laparoscopy. The DH orifice was located in the left crus of the diaphragm, and it was separated from the esophageal hiatus. These findings showed that this DH was a PH. The PH was repaired with primary suturing, and a hiatoplasty was performed. Toupet fundoplication was performed with a 270 degrees posterior wrap of the gastric fornix. The patient has remained asymptomatic a year after surgery without any complications. <br> Clinical discussion: 3D laparoscopy provides significant advantages in surgeries requiring precise suturing. PH repairs require complex procedures, including mesh repair or suturing. Approximately 44 % of PH cases also necessitate fundoplication. 3D laparoscopy was useful for the present case. <br> Conclusions: A rare PH and a symptomatic type 1 hiatal hernia were repaired with 3D laparoscopy, which is helpful for PH treatment in cases requiring complicated procedures. 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.<br> 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.<br> 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.<br> 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.

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.<br> 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.<br> 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).<br> 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.

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.

Springer Science and Business Media LLC Acta Medica Okayama 1612-9059 20 3 2023 Outcomes of solitary postoperative recurrence of esophageal squamous cell carcinoma diagnosed with FDG-PET/CT and treated with definitive radiation therapy 548 556 EN Hiroki Ihara Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yoshio Department of Proton Beam Therapy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichi Sugiyama Department of Proton Beam Therapy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Hashimoto Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Akagi Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hiraki Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Surgical resection of esophageal cancer is frequently performed to achieve a complete cure. However, the postoperative recurrence rate is 36.8–42.5%, leading to poor prognosis. Radiation therapy has been used to treat recurrences; solitary recurrence has been proposed as a prognostic factor for radiation therapy, though its significance is unclear. 18F-fluorodeoxyglucose positron emission tomography is a highly accurate diagnostic modality for esophageal cancer. This retrospective study aimed to analyze the outcomes of solitary postoperative recurrences of esophageal squamous cell carcinoma diagnosed with 18F-fluorodeoxyglucose positron emission tomography and treated with definitive radiation therapy.<br> Methods We examined 27 patients who underwent definitive radiation therapy for single or multiple postoperative recurrences of esophageal squamous cell carcinoma between May 2015 and April 2021. 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed within 3 months before the commencement of radiation therapy. Kaplan–Meier, univariate, and multivariate analyses were performed to examine the overall survival and identify potential prognostic factors.<br> Results The 1-, 2-, and 3-year overall survival rates were 85.2%, 62.6%, and 47.3%, respectively, and solitary recurrence was the only significant factor associated with overall survival (P = 0.003). The 1-, 2-, and 3-year overall survival rates in patients with solitary recurrence were 91.7%, 80.2%, and 80.2%, respectively, and in patients with multiple recurrences they were 80.0%, 50.3%, and 25.1%, respectively. Multivariate analysis also showed solitary recurrence as a significant factor for overall survival.<br> Conclusions When diagnosed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography, solitary recurrence appears to have a more favorable prognosis than multiple recurrences. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression 151 161 EN Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Mochizuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida 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 Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66924 Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD 123 134 EN Kyosuke Saeki Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Taiga Kuroi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Division of Transfusion, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66915 Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano 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 Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-0836 626 7999 2024 Oxygen-evolving photosystem II structures during S1–S2–S3 transitions 670 677 EN Hongjie Li Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Eriko Nango Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Shigeki Owada Japan Synchrotron Radiation Research Institute Daichi Yamada Department of Picobiology, Graduate School of Life Science, University of Hyogo Kana Hashimoto Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Fangjia Luo Japan Synchrotron Radiation Research Institute Rie Tanaka RIKEN SPring-8 Center Fusamichi Akita Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Koji Kato Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Jungmin Kang RIKEN SPring-8 Center Yasunori Saitoh Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Shunpei Kishi Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Huaxin Yu Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Naoki Matsubara Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Hajime Fujii Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Michihiro Sugahara Japan Synchrotron Radiation Research Institute Mamoru Suzuki Institute for Protein Research, Osaka University Tetsuya Masuda Division of Food and Nutrition, Faculty of Agriculture, Ryukoku University Tetsunari Kimura Department of Chemistry, Graduate School of Science, Kobe University Tran Nguyen Thao Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Shinichiro Yonekura Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Long-Jiang Yu Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Takehiko Tosha RIKEN SPring-8 Center Kensuke Tono Japan Synchrotron Radiation Research Institute Yasumasa Joti Japan Synchrotron Radiation Research Institute Takaki Hatsui Japan Synchrotron Radiation Research Institute Makina Yabashi Japan Synchrotron Radiation Research Institute Minoru Kubo Department of Picobiology, Graduate School of Life Science, University of Hyogo So Iwata RIKEN SPring-8 Center Hiroshi Isobe Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Kizashi Yamaguchi Center for Quantum Information and Quantum Biology, Osaka University Michihiro Suga Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1,2,3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4,5,6,7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 130 7 2024 Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus 1187 1195 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Ohtani Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).<br> Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).<br> Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.<br> Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 Bundling of collagen fibrils influences osteocyte network formation during bone modeling 22028 EN Mana Hashimoto Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruka Takahashi Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaori Tabata-Okubo Department of Orthodontics, Okayama University Hospital Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Kazuaki Tokunaga Nikon Corporation Haruka Matsumori Nikon Corporation Yoshihito Ishihara Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Kaku Division of Bio‑prosthodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences, Niigata University Tadahiro Iimura Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University Toru Hara Research Center for Structural Materials, National Institute for Materials Science Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 0021-4922 62 12 2023 Photoelectron holographic evidence for the incorporation site of Se and suppressed atomic displacement of the conducting layer of La(O,F)BiSSe 125001 EN YaJun Li Engineering Research Center of Integrated Circuit Packaging and Testing, Ministry of Education, Tianshui Normal University ZeXu Sun Nara Institute of Science and Technology (NAIST) Noriyuki Kataoka Graduate School of Natural Science and Technology, Okayama University Taro Setoguchi Graduate School of Natural Science and Technology, Okayama University Yusuke Hashimoto Nara Institute of Science and Technology (NAIST) Soichiro Takeuchi Nara Institute of Science and Technology (NAIST) Shunjo Koga Nara Institute of Science and Technology (NAIST) Kazuhisa Hoshi Department of Physics, Tokyo Metropolitan University Yoshikazu Mizuguchi Department of Physics, Tokyo Metropolitan University Tomohiro Matsushita Nara Institute of Science and Technology (NAIST) Takanori Wakita Graduate School of Natural Science and Technology, Okayama University Yuji Muraoka Graduate School of Natural Science and Technology, Okayama University Takayoshi Yokoya Graduate School of Natural Science and Technology, Okayama University La(O,F)BiS2-xSex is a layered material that is considered to be a candidate exotic superconductor as well as a promising thermoelectrical material. We performed soft X-ray photoelectron holography to study the Se incorporation site and the local atomic arrangement of the conducting layer. A comparison of the experimental holograms with the simulated holograms indicates that Se atoms preferentially occupy the S sites in the conducting Bi–S plane of La(O,F)BiS2. A comparison between the state-of-the-art holographic reconstructions of La(O,F)BiSSe and La(O,F)BiS2 suggests that Se substitution suppresses the displacement of S atoms in La(O,F)BiS2. These results provide photoelectron holographic evidence for the Se incorporation site and the Se-induced suppression of in-plane disorder. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males 635 645 EN Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Kazunori Okamura Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Masaki Hasegawa Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Satoshi Tanaka Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Shusaku Kanai Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Original Article 10.18926/AMO/66156 In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis 545 552 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shouichi Tanaka Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Takao Tsuzuki Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Koji Miyahara Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital Shin Negishi Department of Gastroenterology, Kagawa Prefectural Central Hospital Shogen Ohya Kawaguchi Medical Clinic Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65978 To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries 499 509 EN Yuji Hatakeyama Department of Orthopaedic Surgery, Akita Red Cross Hospital Michio Hongo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Tadato Kido Department of Orthopaedic Surgery, Akita Rosai Hospital Masakazu Urayama Department of Orthopaedic Surgery, Ogachi Central Hospital Yuji Kasukawa Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Hiroshi Sasaki Department of Orthopaedic Surgery, Noshiro Kousei Medical Center Toshiaki Aizawa Department of Orthopaedic Surgery, Kitaakita Municipal Hospital Daisuke Kudo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Ryota Kimura Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Yuichi Ono Department of Orthopaedic Surgery, Akita Red Cross Hospital Fumihito Kasama Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65972 This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Childcare and Child Development in Japan 479 490 EN Akiko Murata Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Miyaji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/65970 For decades, the notion has persisted in developed countries that exclusive care by the mothers is best for the development of children up to 3 years of age. To examine the veracity of this “myth of the first three years” in Japan, we examined the effects of childcare facility use for children younger than 3 years on their development using the cohorts of the Longitudinal Survey of Newborns in the 21st Century conducted in Japan. Of the 47,015 respondents to the survey, we studied the children of 5,508 mothers with university/professional education to evaluate the relationships between primary early (< 2.5 years) childcare providers during weekday daytime hours and specific development indices for the ages of 2.5, 5.5, and 8 years. At the age of 2.5 and 5.5 years, children attending childcare facilities were judged as having more advanced developmental behaviors by their parents, such as being able to compose a two-word sentence (adjusted odds ratio [aOR]: 0.22) or to express emotions (aOR: 0.81), compared with those cared for by mothers. However, at the age of 8 years, children who attended childcare facilities as infants < 2.5 years showed more aggressive behavior in interrupting people (aOR: 1.20) and causing disturbances in public (aOR: 1.26) than those cared for by mothers (after adjustment for numerous child and parental factors). Although these results are generally consistent with previous studies, issues potentially involved with problem behavior such as quality of childcare require further investigation, as does the case of children of mothers with more modest educational attainment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 An Assessment Rubric for a Resident Training Program in Surgery: A Single-Institution Experience 451 460 EN Atsushi Okita Department of Surgery, Okayama City Hospital Kazunori Tsukuda Department of Surgery, Okayama City Hospital Hideo Ino Center for Education in Medicine and Health Science, Okayama University Ema Mitsui Department of Surgery, Okayama City Hospital Nanami Ikeya Department of Surgery, Okayama City Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Nobuji Yokoyama Department of Surgery, Okayama City Hospital Aubra Bulin Discovery Program for Global Learners, Okayama University Original Article 10.18926/AMO/65967 Using a Collaborative Action Research model, our research team established a one-month clinical resident training program for first- and second-year clinical residents. We created and implemented an assessment rubric to assess the residents’ progress toward independent practice in surgery, and thereby, to evaluate the program itself. The program included training in three areas: basic techniques and procedures in the operating room, surgical ward management, and academic activities. The rubric measured the residents’ performance according to three achievement levels: Level 1 (demonstration), Level 2 (active help) and Level 3 (passive help). The program and rubric implementation began in June 2019 and continued until March 2020, when the program outcomes and shortcomings were analyzed. Among nineteen clinical residents, a total of nine clinical residents participated in the study. Most participants reached achievement Level 3 for their performance of basic techniques in the operating room. Finally, we discussed ideas for improvement and drafted plans for an improved rubric to complete the action research cycle. Our research team found the rubric to be a useful tool in evaluating the status of the new clinical resident training program. 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.<br> 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.<br> 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.<br> 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.

MDPI Acta Medica Okayama 2071-1050 15 18 2023 The Relationship between the Evaluation of Public Transport Services and Travel-Based CO2 Emissions from Private Transport Modes in Regional and Metropolitan Areas in Japan 13296 EN Shreyas Pradhan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takehito Ujihara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Seiji Hashimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Promoting public transport use is expected to contribute to reducing CO2 emissions in the transport sector. Using Okayama City and Central Tokyo as representative case studies of regional and metropolitan areas in Japan, this study examines the impact of the evaluation of the 'hard' and 'soft' attributes of rail and bus services on the overall evaluation. This study then explores the relationship between the overall evaluation and usage frequency of rail and bus services, as well as the relationship between the usage frequency and travel-based CO2 emissions from private transport modes. Furthermore, this study investigates whether the emissions cause differences in the evaluation of the 'hard' and 'soft' attributes of public transport services. The findings suggest prioritising an improvement in 'hard' rather than 'soft' attributes in order to reduce emissions through the use of public transport in regional areas. However, in metropolitan areas, no relationship was found between the evaluation of public transport services and emissions, presumably because of the lower ownership rate of private cars that residents can use freely and the markedly higher level of rail and bus services. This study provides a methodological reference for analysing the potential to reduce travel-based emissions from private transport modes by enhancing public transport service contents. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 A Case of Acute Zonal Occult Outer Retinopathy in which Oct en Face Imaging Was Useful for Diagnosis and Follow-up 433 437 EN Ryuki Ono Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65756 A 23-year-old woman presented with a 1-month history of visual abnormalities in her right eye. A visual field test revealed temporal abnormalities in the right eye. Optical coherence tomography revealed an indistinct ellipsoid zone (EZ) on the B-scan image and hyporeflective areas in the EZ layer on the en face image in the right eye. We diagnosed the patient with acute zonal occult outer retinopathy. Visual field tests and B-scan images improved to almost normal at 6 months, but hyporeflective areas remained on the en face images. Thus, en face images may be more sensitive at detecting abnormalities in the outer retina than other modalities. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia 395 405 EN Marko Pavlovic University Hospital Center Mostar, University of Mostar Dragan Babic University Hospital Center Mostar, University of Mostar Pejana Rastovic University Hospital Center Mostar, University of Mostar Jurica Arapovic University Hospital Center Mostar, University of Mostar Marko Martinac Health Care Center Mostar, University of Mostar Sanja Jakovac University Hospital Center Mostar, University of Mostar Romana Barbaric University Hospital Center Mostar, University of Mostar Original Article 10.18926/AMO/65750 We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=−0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=−0.258, t=−2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=−0.247, p=0.019) and antipsychotic treatment duration (ρ=−0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 9 1 2023 Adenocarcinoma arising from widespread heterotopic gastric mucosa in the cervicothoracic esophagus: a case report 132 EN Shohei Nogi 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 Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological 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 Yasuhiro Shirakawa Department of Surgery, Hiroshima City Hiroshima Citizens Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis.<br> Case presentation　A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months.<br> Conclusions　Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM. 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).<br> 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.<br> 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.<br> 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.

Springer Acta Medica Okayama 2198-7793 9 1 2023 Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report 119 EN Tasuku Matsumoto 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 Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological 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 Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT.<br> Case presentation　A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment.<br> Conclusion　A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Oncolytic virus–mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer EN Hiroyuki ARAKI 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 Inhibiting S100A8/A9 attenuates airway obstruction in a mouse model of heterotopic tracheal transplantation EN Dai SHIMIZU Graduate School 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 134 3 2022 令和３年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 142 144 EN Yoshihiko Kakiuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Withdrawal from Hemodialysis in a Patient with IgD Type Multiple Myeloma: A Case-based Review 221 225 EN Hiroki Iriyoshi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Ken-ei Sada Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Atsushi Miyauchi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Hirotaka Yamamoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Daisuke Hashimoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shigeru Nojima Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shingo Yamanaka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Masafumi Kawamura Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Satoshi Oka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Case Report 10.18926/AMO/65154 Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Evaluating the Coping Behavior of Children with Psychosomatic Disorders under Frustrating Situations Simulated Using the Rosenzweig Picture-Frustration Study 185 192 EN Akiko Sugihara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makiko Horiuchi Clinical Psychology section, Department of Medical Support, Okayama University Hospital Department of Medical Support Mayumi Yabe Clinical Psychology section, Department of Medical Support, Okayama University Hospital Department of Medical Support Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, 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 Original Article 10.18926/AMO/65148 Psychosomatic disorders are influenced by psychosocial factors such as interpersonal relationships. Coping behaviors, especially in frustrating situations, reflect a patient’s ability to cope with stress, and it is important to assess these behaviors for the treatment of psychosomatic diseases. This study aimed to clarify the interpersonal relationships and coping behaviors of pediatric patients with psychosomatic diseases during frustrating situations simulated using the Rosenzweig Picture-Frustration study. This retrospective study included 126 patients (41 male, 85 female) with an average age of 12.9 (6-16) years who were consulted at the Department of Pediatric Psychosomatic Medicine at Okayama University Hospital from 2013 to 2018 and underwent the P-F study. Each score was compared with a standardization sample. The mean group conformity rating did not differ significantly between the participants and healthy children. Compared with healthy children, those with psychosomatic diseases were less likely to explain their perspective. The children with psychosomatic disorders responded to frustrating situations in a sensible and age-appropriate manner. However, they were less likely to respond by explaining their perspective to protect themselves. 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.

American Chemical Society (ACS) Acta Medica Okayama 1932-7447 127 5 2023 Uniform Formation of a Characteristic Nanocomposite Structure of Biogenous Iron Oxide for High Rate Performance as the Anode of Lithium-Ion Batteries 2223 2230 EN Masakuni Takahashi Graduate School of Natural Science and Technology, Okayama University Ryo Sakuma Graduate School of Natural Science and Technology, Okayama University Hideki Hashimoto Graduate School of Natural Science and Technology, Okayama University Tatsuo Fujii Graduate School of Natural Science and Technology, Okayama University Jun Takada Graduate School of Natural Science and Technology, Okayama University Recently, Fe2O3 has been considered as an alternative anode material for lithium-ion batteries (LIBs) owing to its high theoretical capacity (approximately 1000 mA h g-1), low cost, and nontoxicity. However, its rate performance remains poor relative to that of the conventional graphite anode. In this study, Fe2O3-based anodes were prepared through the annealing of biogenous Fe2O3 (L-BIOX) samples produced by an aquatic Fe-oxidizing bacterium. The effect of the annealing temperature on the performance of the synthesized Fe2O3-based material as the anode of an LIB was investigated. Electrochemical measurements revealed that the annealed L-BIOX samples at 300-700 degrees C exhibited higher rate performances than the unannealed material. Particularly, the sample annealed at 700 degrees C exhibited the highest capacity among the synthesized materials and showed a higher performance than the previously reported Fe2O3-based anodes. It exhibited a capacity of 923 mA h g-1 even at a high current density of 2 A g-1. After annealing at 700 degrees C and discharging, the synthesized biogenous material had a uniform nanocomposite structure composed of alpha-Fe2O3 nanoparticles dispersed in an amorphous matrix of Li-Si-P oxide. To form this uniform nanostructure, the solid-state diffusion resistance of the Li+ ions in the active material was reduced, which consequently improved the rate performance of the electrode. Therefore, this study provides substantial insights into the development and improvement of the performance of novel Fe2O3-based nanomaterials as the anode of LIBs. No potential conflict of interest relevant to this article was reported.

Lippincott, Williams & Wilkins Acta Medica Okayama 0025-7974 101 50 2022 Safety and efficacy of capsule endoscopy for patients with newly diagnosed Crohn's disease: A multicenter retrospective study e32424 EN Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shiro Oka Department of Gastroenterology and Metabolism, Hiroshima University Hospital Akiko Shiotani Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School Shinichi Hashimoto Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine Sakuma Takahashi Department of Gastroenterology, Kagawa Prefectural Central Hospital Osamu Handa Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School Taro Takami Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine Tomoki Inaba Department of Gastroenterology, Kagawa Prefectural Central Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinji Tanaka Department of Gastroenterology and Metabolism, Hiroshima University Hospital Crohn's disease (CD) is a chronic inflammatory disease that develops at a young age and frequently leads to intestinal resection. Capsule endoscopy (CE) can directly and non-invasively inspect the entire small bowel mucosa. We suspected that CE could be a good diagnostic tool for detecting CD in young patients. The aim of this study was to investigate the safety and efficacy of CE in patients with newly diagnosed CD and to evaluate the CE findings, especially in the upper small bowel of young patients. We retrospectively investigated 32 patients with newly diagnosed CD from 5 institutions. Patient characteristics, clinical course, and characteristics of CE findings were analyzed. The total small intestine observation rate was 93%, and the retention rate was 3% (1/32). No abnormality was identified by ileocolonoscopy in 46% (15/32), and transition of small bowel lesions (TSL) was found in 35% (12/34) of the patients. The frequency of longitudinal ulcers and cobblestones in the upper small intestine was significantly higher in younger patients (<= 20 years). Moreover, positive findings in the upper small intestine were predominantly observed in younger patients (<= 20 years). CE for patients with newly diagnosed CD was safe and useful, especially for the detection of upper small bowel lesions in young patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 A Case Report of Non-typical Annular Pancreas Diagnosed during Laparoscopic Gastric Surgery 91 95 EN Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuch Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64368 An annular pancreas is a rare anomaly of the pancreas, defined as pancreatic tissue that totally or partly encircles the duodenum, usually the descending portion. A 76-year-old man who was diagnosed with gastric cancer cT3N0M0 Stage IIB underwent laparoscopic distal gastrectomy with D2 lymph node dissection. Intraoperatively, the dorsal half of the duodenal bulb was seen to be half surrounded by the pancreas, and a non-typical annular pancreas was diagnosed. Because of the risk to the pancreas, it was considered impossible to perform anastomosis by a linear stapler as in the usual laparoscopic procedure. Therefore, we performed laparoscopically assisted distal gastrectomy and Billroth-I reconstruction using a circular stapler, and the surgery was completed without difficulties. His postoperative course was good despite the development of a pancreatic fistula, which was an International Study Group for Pancreas Fistula biochemical leak. Some APs can be diagnosed preoperatively, but the rarer subtypes such as ours are more difficult to visualize on imaging. In gastrectomy, it is both oncologically important and technically challenging to perform lymph node dissection around the pancreas. In this case with an especially proximal pancreas, a circular stapler was considered better suited for gastroduodenal anastomosis and required a broader field than that afforded by laparoscopy. A case of non-typical annular pancreas diagnosed during laparoscopic gastric surgery is described. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Scattered Tiny Whitish Protrusions in the Stomach Are a Clue to the Diagnosis of Autoimmune Gastritis 75 80 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hamada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64365 Herein, we report two patients with autoimmune gastritis who had undergone multiple esophagogastroduodenoscopy procedures for 17 and 9 years, respectively, before their diagnosis. Instead, they had been diagnosed with and treated for Helicobacter pylori-associated gastritis. The correct diagnosis was made when scatterings of tiny whitish protrusions in the gastric mucosa were detected on esophagogastroduodenoscopy. Our findings suggest that scattered tiny whitish bumps may be a clue to the diagnosis of autoimmune gastritis. 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 Fetal Cerebellar Growth Curves Based on Biomathematics in Normally Developing Japanese Fetuses and Fetuses with Trisomy 18 645 650 EN Katsuhiko Tada Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Yasunari Miyagi Medical Data Labo Reina Komatsu Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital Naoki Okimoto Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Saya Tsukahara Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Yoko Tateishi Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Naomi Ooka Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Mizuho Yoshida Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Kazumasa Kumazawa Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Original Article 10.18926/AMO/64114 We used biomathematics to describe and compare cerebellar growth in normally developing and trisomy 18 Japanese fetuses. This retrospective study included 407 singleton pregnancies with fetuses at 14-39 weeks of gestation and 33 fetuses with trisomy 18 at 17-35 weeks. We used ultrasonography to measure fetal transverse cerebellar diameter (TCD) and anteroposterior cerebellar diameter (APCD). We hypothesized that cerebellar growth is proportional to cerebellar length at any given time point. We determined the formula L(t) ≒Keat+r, where e is Napier’s number, t is time, L is cerebellar length, and a, K, and r are constants. We then obtained regression functions for each TCD and APCD in all fetuses. The regression equations for TCD and APCD values in normal fetuses, expressed as exponential functions, were TCD(t)=27.85e0.02788t−28.62 (mm) (adjusted R2=0.997), and APCD(t)=324.29e0.00286t−322.62 (mm) (adjusted R2=0.995). These functions indicated that TCD and APCD grew at constant rates of 2.788%/week and 0.286%/week, respectively, throughout gestation. TCD (0.0153%/week) and APCD (0.000430%/week) grew more slowly in trisomy 18 fetuses. This study demonstrates the potential of biomathematics in clinical research and may aid in biological understanding of fetal cerebellar growth. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Clinical moderators of response to nalmefene in a randomized-controlled trial for alcohol dependence: An exploratory analysis EN Nozomu HASHIMOTO 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 Effects of Model-Based Iterative Reconstruction in Low-Dose Paranasal Computed Tomography: A Comparison with Filtered Back Projection and Hybrid Iterative Reconstruction 511 517 EN Hayato Tomita Department of Radiology, St. Marianna University School of Medicine Kenji Kuramochi Department of Radiology, St. Marianna University School of Medicine Atsuko Fujikawa Department of Radiology, St. Marianna University School of Medicine Hirotaka Ikeda Department of Radiology, Fujita Health University School of Medicine Midori Komita Department of Radiology, St. Marianna University School of Medicine Yoshiko Kurihara Department of Radiology, Machida Municipal Hospital Yasuyuki Kobayashi Department of Advanced Biomedical Imaging Informatics, St. Marianna University School of Medicine Hidefumi Mimura Department of Radiology, St. Marianna University School of Medicine Original Article 10.18926/AMO/64031 Iterative reconstruction (IR) improves image quality compared with filtered back projection (FBP). This study investigated the usefulness of model-based IR (forward-projected model-based iterative reconstruction solution [FIRST]) in comparison with FBP and hybrid IR (adaptive iterative dose reduction three-dimensional processing [AIDR 3D]) in low-dose paranasal CT. Twenty-four patients with paranasal sinusitis who underwent standard-dose CT (120 kV) and low-dose CT (100 kV) scanning before and after medical treatment were enrolled. Standard-dose CT scans were reconstructed with FBP (FBP120), and low-dose CT scans with FBP (FBP100), AIDR 3D, and FIRST. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in three anatomical structures and effective doses were compared using Mann–Whitney U test. Two radiologists independently evaluated the visibility of 16 anatomical structures, overall image quality, and artifacts. Effective doses in lowdose CT were significantly reduced compared with those in standard-dose CT (0.24 vs 0.43 mSv, p<0.001). FIRST achieved significantly higher SNR (p<0.01, respectively) and CNR (p<0.001, respectively) of evaluated structures and significant improvement in overall image quality (p<0.001), artifacts (p<0.001), and visibility related to muscles (p<0.05) compared to FBP120, FBP100, and AIDR 3D. FIRST allowed radiation-dose reduction, while maintaining objective and subjective image quality in low-dose paranasal CT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Current Insights into Mesenchymal Signatures in Glioblastoma 489 502 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomotsugu Ichikawa Department of Neurological Surgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Review 10.18926/AMO/64024 Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2372-7705 27 2022 Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer 3 13 EN Hiroyuki Araki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kajiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adeno-carcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telo-merase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracel-lular adenosine triphosphate and high-mobility group box pro-tein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpres-sion augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0741-238X 2022 Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study EN Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Nakajima Department of Internal Medicine, Nakashima Hospital Masami Hashimoto Hashimoto Kidney Clinic Akihiko Nakamura Osafune Clinic Tomokazu Nunoue Nunoue Clinic Kazuharu Murakami Murakami Clinic Takeshi Hosoya Hosoya Clinic Kiichi Komoto Innoshima General Hospital Takashi Taguchi Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Takaaki Akasaka Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Kazuhito Shiosakai Data Intelligence Department, Daiichi Sankyo Co., Ltd. Kotaro Sugimoto Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Introduction<br> Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment.<br> <br> Methods<br> In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR < 30, 30 to < 300, and 300 to < 1000 mg/gCr). Esaxerenone was initiated at 1.25 mg/day and followed by incremental dose escalation based on BP and serum potassium level monitoring. The treatment period was 12 weeks. The primary endpoint was change in morning home systolic BP/diastolic BP (SBP/DBP) from baseline to end of treatment (EOT). Secondary endpoints included achievement rate of target BP, change in UACR from baseline, and safety.<br> <br> Results<br> In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (− 11.6/− 5.2 mmHg, both p < 0.001) and in all UACR subcohorts (all p < 0.001). The target BP achievement rate was 38.5%. Significant reductions in bedtime home and office BPs were also shown in the total population and all UACR subcohorts. UACR significantly improved from baseline to EOT in the total (− 50.9%, p < 0.001) and all UACR subcohorts (all p < 0.001). Incidence of serum potassium elevation as drug-related treatment emergent adverse events was 2.7%. The change from baseline in estimated glomerular filtration rate (eGFR) was − 4.8 mL/min/1.73 m2.<br> <br> Conclusion<br> Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Molecular-targeted Therapy for Metastatic Renal Cell Carcinoma As First-line Therapy: A Single Institution 13-year Experience 465 472 EN Kensuke Bekku Department of Urology, Hiroshima City Hiroshima Citizens Hospital Takuji Tsugawa Department of Urology, Hiroshima City Hiroshima Citizens Hospital Kazuma Tsuboi Department of Urology, Hiroshima City Hiroshima Citizens Hospital Gaku Noda Department of Urology, Hiroshima City Hiroshima Citizens Hospital Yousuke Inoue Department of Urology, Hiroshima City Hiroshima Citizens Hospital Wataru Murao Department of Urology, Hiroshima City Hiroshima Citizens Hospital Shin Ebara Department of Urology, Hiroshima City Hiroshima Citizens Hospital Original Article 10.18926/AMO/63906 We aimed to identify the role of first-line monotherapy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in patients with metastatic RCC. Eligible patients were categorized into three groups (favorable, intermediate, and poor risk) according to the International Metastatic RCC Database Consortium risk criteria. Overall survival (OS) was the primary endpoint. Survival was compared using the log-rank test. A total of 108 patients were retrospectively analyzed. The numbers of patients in the favorable-, intermediate-, and poor-risk groups were 32 (30%), 66 (61%), and 10 (9%), repestively. The median OS values in the entire cohort was 36 months (95% confidence interval [CI] 29-53). The median OS in the favorable, intermediate, and poor risk groups were 94 months (95% CI: 43-Not reached), 30 months (95% CI: 20-38), and 8 months (95% CI: 0-Not reached), respectively (p<0.05). Prior nephrectomy, clear cell histology, clinical T stage ≤2, no metastasis at the time of diagnosis, nivolumab beyond first-line therapy, and objective response to VEGFR-TKIs were factors significantly prolonging OS on univariate analysis. VEGFR-TKI monotherapy as first-line therapy was an effective treatment option for patients with metastatic clear cell RCC with favorable risk. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 Verrucous carcinoma of the esophagus with complete response after chemoradiotherapy 128 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological 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 Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Sakurama 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background : Verrucous carcinoma of the esophagus (VCE) is a rare tumor that is difficult to diagnose. In most cases, biopsies show nonspecific inflammatory and hyperkeratotic changes and do not show malignant findings. Most VCEs are slowly growing, locally advanced tumors with few metastases. Treatments for VCE are the same as for normal esophageal cancer, involving combined chemotherapy, surgical resection, and radiation therapy. However, it has been reported that VCE has a poor response to radiation or chemoradiotherapy (CRT). A case of VCE with complete response (CR) after CRT is presented. <br> Case presentation : A 70-year-old man was found to have white, irregular esophageal mucosa 4 years earlier. He had been followed up as an outpatient as having candidal esophagitis. However, his tumor grew gradually, and biopsy was performed by endoscopic mucosal resection (EMR). He was finally diagnosed with VCE. He had no metastases to distant organs, but some lymph node metastases were suspected. The tumor invaded his left bronchus. The esophagostomy and gastrostomy were constructed as emergent procedures. The patient then underwent definitive CRT. 4 weeks after the end of CRT, two-stage esophagectomy was performed. First, he underwent esophagectomy with thoracic lymph node dissection. A latissimus dorsi flap was patched to the bronchus after primary suture of the hole. 6 weeks later, reconstruction of the gastric tube was performed through the antethoracic route. The pathological findings showed CR to CRT, with no proliferative cancer cells in the specimen. The patient has had no recurrence for three and half years after the resection. <br> Conclusions : We presented a locally advanced VCE that achieved CR to CRT. In cases that have some difficulty for local resection, CRT might be an appropriate treatment for VCE. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Rhabdomyolysis with Multiple Electrolyte Imbalances under Proton Pump Inhibitor Treatment after Total Thyroidectomy 339 342 EN Akihiko Yano Department of General Medicine, Kochi Health Sciences Center Ken-ei Sada Department of General Medicine, Kochi Health Sciences Center Tsutomu Sawada Department of General Medicine, Kochi Health Sciences Center Hideki Ito Department of General Medicine, Kochi Health Sciences Center Hiroko Yano Department of General Medicine, Kochi Health Sciences Center Tatsuya Ikeda Department of General Medicine, Kochi Health Sciences Center Case Report 10.18926/AMO/63745 A 90-year-old man presented with muscle weakness, difficulty concentrating, and dysphagia. About eighteen months prior to presentation, lansoprazole had been initiated to prevent stress ulcers; he also had a history of total thyroidectomy due to papillary thyroid cancer ten years prior. Laboratory findings were as follows: K 2.4 mEq/L, Ca 3.7 mg/dL, Mg 1.3 mg/dL, CK 5386 U/L, and intact PTH (iPTH) 14 pg/mL. Rhabdomyolysis with multiple electrolyte imbalances under proton pump inhibitor (PPI) treatment was diagnosed. We initiated intravenous hydration and electrolyte supplementation with discontinuation of PPI. After discontinuing PPI, the patient’s serum magnesium, potassium, and calcium levels normalised with oral vitamin D and calcium supplementation. PPIs can cause hypocalcaemia and hypokalaemia via hypomagnesemia; hypocalcaemia is also a common postoperative complication of thyroidectomy. Careful monitoring of electrolyte levels is required in patients with long-term PPI treatment, especially in post-thyroidectomy cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Successful Treatment of Atypical Femoral Fracture with Bowed Femur Using Contralateral Intramedullary Nail Combined with Early Daily Teriparatide 333 338 EN Manabu Akagawa Department of Orthopedic Surgery, Omagari Kosei Medical Center Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroyuki Tsuchie Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yuji Kasukawa Department of Orthopedic Surgery, Akita University Graduate School of Medicine Takashi Kawaragi Department of Orthopedic Surgery, Omagari Kosei Medical Center Itsuki Nagahata Department of Orthopedic Surgery, Omagari Kosei Medical Center Masazumi Suzuki Department of Orthopedic Surgery, Omagari Kosei Medical Center Takayuki Yoshikawa Department of Orthopedic Surgery, Omagari Kosei Medical Center Toshiki Abe Department of Orthopedic Surgery, Omagari Kosei Medical Center Yoichi Shimada Department of Orthopedic Surgery, Akita University Graduate School of Medicine Case Report 10.18926/AMO/63744 We report a case of atypical femoral fracture achieving early fracture union with combination therapy comprising contralateral nail and immediate teriparatide injection. Fracture union of atypical fractures is often delayed due to bowing deformity and bone metabolic disorders. Combination treatment that takes both problems into consideration represents a useful treatment option for atypical femoral fracture. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model EN Kohei Hashimoto 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 Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells EN Tomoya Masuda 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 2 2022 Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells 203 215 EN Tomoya Masuda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuuri Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ieda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda 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 Yasuo Urata Oncolys BioPharma Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63425 The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Relation between Prolonged Sedentary Bouts and Health-Related Quality of Life in Patients on Chronic Hemodialysis 113 119 EN Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Hiroyuki Nishi Innoshima General Hospital Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Hiroo Hashimoto Innoshima General Hospital Original Article 10.18926/AMO/63404 This study aimed to investigate the link between prolonged sedentary bouts and health-related quality of life (QOL) in patients on chronic hemodialysis (CHD). A total of 84 outpatients on CHD, aged 71.6±11.8 years, were enrolled in this cross-sectional study. Parameters for prolonged sedentary bouts [i.e., ≧ 30 min (% and bout) and ≧ 60 min (% and bout)] were measured using a triaxial accelerometer. Health-related QOL (HRQOL) was evaluated by the Euro-QOL (EQ-5D). Clinical parameters were obtained from medical records. Relatively prolonged sedentary bouts (%) were 44.0±18.2 (≧ 30 min) and 29.8±16.5 (≧ 60 min) for total days. Prolonged sedentary bouts (bouts) were 6.2±2.7 (≧ 30 min) and 2.7±1.6 (≧ 60 min) for total days. EQ-5D scores were 0.728±0.220. All prolonged sedentary bout parameters were negatively correlated with EQ-5D scores, except for prolonged sedentary bouts (≧ 60 min) (min) and relatively prolonged sedentary bouts (%) on hemodialysis days. Multiple regression analysis showed that prolonged sedentary bout parameters were an important factor in EQ-5D scores even after adjusting for confounding factors for total and non-hemodialysis days. Our results suggested that prolonged sedentary bouts were closely associated with HRQOL in patients on CHD, especially on non-hemodialysis days. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2589-0042 25 3 2022 Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer's disease 103869 EN Nanaka Kaneshiro Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Komai Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Imaoka Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsuya Ikeda Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuji Kamikubo Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine Takashi Saito Department of Neurocognitive Science, Nagoya City University Graduate School of Medical Sciences Takaomi C. Saido Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science Taisuke Tomita Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo Tadafumi Hashimoto Department of Neuropathology, Graduate School of Medicine, The University of Tokyo Takeshi Iwatsubo Department of Neuropathology, Graduate School of Medicine, The University of Tokyo Takashi Sakurai Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine Takashi Uehara Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Endosomal anomalies because of vesicular traffic impairment have been indicated as an early pathology of Alzheimer'vertical bar disease (AD). However, the mechanisms and therapeutic targets remain unclear. We previously reported thatbCTF, one of the pathogenic metabolites of APP, interacts with TMEM30A. TMEM30A constitutes a lipid flippase with P4-ATPase and regulates vesicular trafficking through the asymmetric distribution of phospholipids. Therefore, the alteration of lipid flippase activity in AD pathology has got attention. Herein, we showed that the interaction between beta CTF and TMEM30A suppresses the physiological formation and activity of lipid flippase in AD model cells, A7, and App(NLG-F/NLG-F) model mice. Furthermore, the T-RAP peptide derived from the beta CTF binding site of TMEM30A improved endosomal anomalies, which could be a result of the restored lipid flippase activity. Our results provide insights into the mechanisms of vesicular traffic impairment and suggest a therapeutic target for AD. No potential conflict of interest relevant to this article was reported.

AME Publishing Company Acta Medica Okayama 2072-1439 13 10 2021 Meticulous closure of collateral vessels in the perihilar mediastinal pleura to control intraoperative bleeding during lung transplantation for pulmonary hypertension 5658 5669 EN Haruchika Yamamoto 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 Kentaro Imanishi 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 Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinji Otani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Masaomi Yamane 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 Background: Massive blood transfusion compensating hemorrhage during lung transplantation (LT) results in primary graft dysfunction (PGD) and worse outcomes after LT. Collateral vessels in the perihilar mediastinal pleura could be the source of hemorrhage during LT in patients with pulmonary hypertension (PH). The purpose of this study was to examine the effect of closure with hemoclips of the vessels in the perihilar mediastinal pleura on the risk of intraoperative hemorrhage and outcomes after LT in patients with PH.<br> <br> Methods: We retrospectively reviewed 80 patients who underwent LT, including 13 patients with primary PH, 29 patients with secondary PH, and 38 patients with non-PH.<br> <br> Results: The median number of hemoclips was significantly higher in the primary PH group than in the non-PH group (P=0.0045) or secondary PH group (P=0.0060). The intraoperative blood loss, transfusion volume, maximum PGD grade, and the 30-day and 90-day mortality rates in the primary PH group were equivalent to those in the other two groups.<br> <br> Conclusions: Meticulous closure of collateral vessels in the perihilar mediastinal pleura during LT in patients with primary PH allowed intraoperative hemorrhage to be controlled and might be associated with acceptable mortality rate in these patients similar to that of LT in patients with other diseases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Morphological Changes and Durability of Skin and Mucosal Flaps in Intraoral and Pharyngeal Reconstructions: Long-term Follow-up and Literature Review for Potential Second Carcinomas 725 734 EN Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Ota Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Narushi Sugiyama Department of Plastic and Reconstructive Surgery, Japanese Red Cross Okayama Hospital Satoshi Onoda Department of Plastic and Reconstructive Surgery, Kagawa Rosai Hospital Takuma Makino Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiko Takeda Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Nobuyoshi Mizukawa Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Original Article 10.18926/AMO/62813 The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify the morphological changes, long-term durability, and potential for secondary carcinogenesis in such tissues. In our single-center study, the rough morphological changes in 54 cases of intraoral and pharyngeal skin and mucosal flaps were evaluated more than 10 years after flap transfer. In addition, the literature on the development of second carcinomas from skin flaps was reviewed. The mean follow-up period for transferred flaps was 148 months. The reconstruction areas and the probability of morphological changes were significantly correlated (p=0.006), especially in cases with tongue, lower gingiva, and buccal mucosal reconstruction. Free jejunal flap surfaces were well maintained, whereas tubed skin flaps showed severe morphological changes in cases with pharyngeal reconstruction. None of the flaps in our series developed second primary carcinomas. Skin flaps generally had good durability for > 10 years in intraoral environments, while mucosal flaps had better durability for pharyngeal reconstruction. Second squamous carcinomas arising from skin flaps are extremely rare; however, surgeons should take this possibility into consideration and conduct meticulous and long-term follow-up. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial 663 667 EN Takuya Sadahira Department of Urology, Okayama University Hospital Yuki Maruyama Department of Urology, Okayama University Hospital Yoshiki Hiyama Hakodate Goryoukaku Hospital Hiroyuki Kitano Hiroshima University Hospital Hiroki Yamada Jikei University Katsushika Medical Center Takayuki Goto Kyoto University Hospital Tsubasa Kondo Nagasaki University Hospital Katsumi Shigemura Kobe University Hospital Yosuke Mitsui Department of Urology, Okayama University Hospital Takehiro Iwata Department of Urology, Okayama University Hospital Kohei Edamura Department of Urology, Okayama University Hospital Motoo Araki Department of Urology, Okayama University Hospital Masami Watanabe Department of Urology, Okayama University Hospital Tadasu Takenaka Japanese Red Cross Okayama Hospital Jun Teishima Hiroshima University Hospital Yasuyoshi Miyata Nagasaki University Hospital Kiyohito Ishikawa Fujita Health University Hospital Ei-Ichiro Takaoka Internationla University of Health and Welfare Hospital Jun Miyazaki Internationla University of Health and Welfare Hospital Satoshi Takahashi Sapporo Medical University Hospital Naoya Masumori Sapporo Medical University Hospital Hiroshi Kiyota Jikei University Katsushika Medical Center Masato Fujisawa Kobe University Hospital Shingo Yamamoto Hyogo College of Medicine College Hospital Takafumi Sakuma Okayama Medical Center Norihiro Kusumi Okayama Medical Center Takaharu Ichikawa Okayama Medical Center Toyohiko Watanabe Department of Urology, Okayama University Hospital Yoshitsugu Nasu Okayama Rosai Hospital Masaya Tsugawa Okayama City General Medical Center Yasutomo Nasu Department of Urology, Okayama University Hospital Koichiro Wada Department of Urology, Okayama University Hospital Clinical Study Protocol 10.18926/AMO/62782 The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Added Diagnostic Value of Cerebrospinal Fluid Carcinoembryonic Antigen in a Patient with Leptomeningeal Carcinomatosis as the Initial Manifestation of Gastric Cancer 659 661 EN Riku Ino Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Ken-ei Sada Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Atsushi Miyauchi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Daisuke Hashimoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shigeru Nojima Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shingo Yamanaka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Masafumi Kawamura Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Case Report 10.18926/AMO/62781 A 77-year-old woman with no history of malignancy presented with anorexia and bilateral lower extremity weakness. Her consciousness level worsened daily, so we performed a lumbar puncture. Cerebrospinal fluid (CSF) analysis indicated meningitis, but three rounds of CSF cytology showed no malignant cells. The patient’s carcinoembryonic antigen (CEA) level was highly elevated in CSF, but normal in serum. Through gadolinium-enhanced brain/spinal magnetic resonance imaging and gastrointestinal endoscopy, she was diagnosed with leptomeningeal carcinomatosis (LC) from gastric cancer. CEA level in CSF facilitated the diagnosis of LC from gastric cancer because there were no malignant cells on CSF cytology. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Recurrence of Hypoglycemic Coma in a Patient with Anorexia Nervosa 631 636 EN Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mai Yamane Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reina Son 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 Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Minao Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Edahiro Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/62776 Anorexia nervosa (AN) is occasionally complicated with hypoglycemic coma, which may cause sudden death by unknown mechanisms. We present the case of a 36-year-old woman with recurrent comas and a nineteen-year history of AN. She was found in a coma with remarkable hypoglycemia (28 mg/dL). Her BMI was 11.1 kg/m2. Endocrine workup revealed extremely low serum levels of glucagon, IGF-I and insulin. Asymptomatic hypoglycemia occurred with liver injury in the refeeding process. An aberrant glucose metabolism due to liver damage might have been involved in her susceptibility to hypoglycemia. This case suggests a possible mechanism of hypoglycemic coma in AN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Multidisciplinary Approach to Reduce Postoperative Complications and Improve the Activity of Patients with Hip Fracture: A 24-month Follow-up Survey 595 600 EN Norio Imai Department of Orthopedic Surgery, Niigata Prefectural Shibata Hospital Naoto Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Ken Suda Department of Orthopedic Surgery, Niigata Prefectural Shibata Hospital Hayato Suzuki Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/62772 Multidisciplinary approaches such as fracture liaison services (FLS) have been introduced in some countries to reduce medical complications and secondary fractures in patients with fragility hip fracture. We aimed to investigate outcomes in patients with fragility hip fracture following the introduction of FLS. Patients > 50 years old who experienced fragility hip fractures between January 1, 2015 and December 31, 2017 were enrolled, and divided into a control group (without FLS; 94 patients) and FLS group (373 patients). We found that the time from injury to surgery decreased significantly from 2.42 to 1.83 days (p = 0.003), the proportion of patients who underwent surgery within 36 h of injury increased significantly (p = 0.014), and the number of cases with complications after admission decreased significantly (p = 0.004) in the FLS group. Patients with a Barthel index ≥ 80 were more common in the FLS than the control group at 6 , 12, and 24 months following injury (p = 0.046 , 0.018, and 0.048, respectively). Multiple logistic regression analysis revealed the factors associated with postoperative complications and death within 12 or 24 months after injury. Our results indicate that FLS contributed to earlier recovery, rehabilitation following surgery and rehabilitation of medical complications following admission; improved patient activity; and decreased secondary hip fractures. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 2 2021 令和２年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 90 92 EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

The American Society of Gene and Cell Therapy Acta Medica Okayama 15250016 29 10 2021 Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles 2920 2930 EN Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Tsumura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 An Elderly Male with Primary Sjögren’s Syndrome Presenting Pleuritis as the Initial Manifestation 539 542 EN Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Oka 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 Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/62409 Primary Sjögren’s syndrome (SS) is an autoimmune disease that usually affects the exocrine glands in mid-dle-aged women. Fifteen percent of SS patients experience severe systemic extraglandular complications, and pleuritis is one of the rare complications of SS. We report the case of an elderly Japanese man who initially pre-sented with a prolonged fever and chest pain and was finally diagnosed with primary SS-associated pleuritis. Of the nine reported cases of primary SS that initially presented with pleuritis, up to six cases were elderly males. This case highlights the complication of pleuritis among elderly males with primary SS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Surgical Treatment of Epiretinal Membrane 403 413 EN Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/62378 Epiretinal membrane (ERM) is a common retinal disease characterized by cellular proliferation and metaplasia that lead to the formation of a pathological fibrocellular membrane immediately superjacent to the inner retinal surface. The vast majority of ERMs are considered idiopathic. However, ERM formation can result from various primary intraocular diseases, including retinal breaks and detachment, retinal vascular diseases, and vitreoretinal inflammatory conditions. Although ERMs are generally asymptomatic or cause mild metamorphopsia and/or a modest decrease in visual acuity, some can cause severe macular distortion and macular edema, resulting in significantly impaired function. Surgical removal of ERM is the only treatment, and improvements in vitrectomy systems have enabled less invasive treatment. However, there are currently no standardized criteria for ERM surgery, and the indications for surgery are determined from the patient’s subjective symptoms. Another problem with ERM surgery is that not all patients show satisfactory postoperative recovery of visual function. Thus, further research is needed to determine the criteria for ERM surgery and methods to improve the postoperative prognosis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Predictors of Hypotension after Adrenalectomy for Pheochromocytoma 345 349 EN Kanae Koyama Department of Urology, Graduate School of Medicine, Ehime University Noriyoshi Miura Department of Urology, Graduate School of Medicine, Ehime University Ryuta Watanabe Department of Urology, Graduate School of Medicine, Ehime University Yuichiro Sawada Department of Urology, Graduate School of Medicine, Ehime University Terutaka Noda Department of Urology, Graduate School of Medicine, Ehime University Kenichi Nishimura Department of Urology, Graduate School of Medicine, Ehime University Seiji Asai Department of Urology, Graduate School of Medicine, Ehime University Tetsuya Fukumoto Department of Urology, Graduate School of Medicine, Ehime University Yutaka Yanagihara Department of Urology, Graduate School of Medicine, Ehime University Yuki Miyauchi Department of Urology, Graduate School of Medicine, Ehime University Tadahiko Kikugawa Department of Urology, Graduate School of Medicine, Ehime University Takashi Saika Department of Urology, Graduate School of Medicine, Ehime University Original Article 10.18926/AMO/62229 The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Gender Expression among Transgender Women in Japan: Support Is Needed to Improve Social Passing as a Woman 323 334 EN Michiyo Furutani Graduate School of Health Sciences, Okayama University Zhou Yu Graduate School of Health Sciences, Okayama University Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/62227 Gender expression is important for transgender women to improve their social passing as women. Herein, a questionnaire about the status of gender expression and support needs was distributed to 54 transgender women aged 17-71 in Japan. Most of the respondents noted that they had found it relatively difficult to handle physical changes and weight gain due to hormone treatment. They also found it difficult to enact and sustain practices such as a feminine use of voice and to use women-only services, whereas practicing and continuing with routine skin and hair care and feminine mannerisms were relatively easy for them. In the questionnaire regarding the support for gender transitioning, many items showed only a small percentage of the transgender women had received the support that they were looking for, and most of their needs for support were not addressed. Some of the factors that increased the respondents’ needs and achievement of gender expression as women included estrogen treatment, sex reassignment surgery, and living as a woman; these aspects met their support needs as well. Gender support professionals need to coordinate and collaborate with specialists in areas such as nutritional guidance and voice training to enable transgender women to improve the extent to which they can socially ‘pass’ as women. No potential conflict of interest relevant to this article was reported.

Oxford Univ Press Acta Medica Okayama 1461-1457 24 5 2020 Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus 367 382 EN Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuji Yada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Hashimoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes' functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Long-term Survival with a Rare Advanced Primary Gastrointestinal Malignant Melanoma Treated with Laparoscopic Surgery/Immune Checkpoint Inhibitor 231 238 EN Motochika Endo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Asano Department of Surgery, Mitoyo general Hospital Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61906 Targeted therapies for malignant melanoma have improved patients’ prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years. Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 A Case of Dual-pathology Hepatocellular Carcinoma (HCC) and Cholangiolocellular Carcinoma (CoCC) after Eradication of Hepatitis C Virus (HCV) Infection 213 218 EN Manabi Miyashita Department of Hepatology, National Hospital Organaization of Iwakuni Clinical Center Yousuke Saragai Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Tsuyoshi Fujimoto Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Shouichi Tanaka Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organaization of Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organaization of Iwakuni Clinical Center Case Report 10.18926/AMO/61903 A 75-year-old Japanese man visited our hospital for further examination of liver tumors. He had a history of successful hepatitis C virus (HCV) eradication and therapy for hepatocellular carcinoma (HCC) at another hospital. Magnetic resonance imaging (MRI) revealed two tumors in the liver. He underwent anterior inferior (S5) and posterior inferior (S6) subsegmentectomy of the liver. Microscopic examination found that one tumor was HCC while the other was cholangiolocellular carcinoma (CoCC). We experienced a rare case of liver cancer with two synchronous pathologies, HCC and CoCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Camouflage Treatment for Skeletal Maxillary Protrusion and Lateral Deviation with Classic-Type Ehlers-Danlos Syndrome 205 212 EN Mitsuhiro Hoshijima Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriaki Kawanabe Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yamashiro Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61902 We herein report the case of a 19-year-old female with a transverse discrepancy, skeletal Class II malocclusion, severe crowding with concerns of classic-type Ehlers-Danlos syndrome (EDS), aesthetics problems and functional problems. The main characteristics of classic EDS are loose-jointedness and fragile, easily bruised skin that heals with peculiar “cigarette-paper” scars. The anteroposterior and transverse skeletal discrepancies can generally be resolved by maxilla repositioning and mandibular advancement surgery following pre-surgical orthodontic treatment. However, this patient was treated with orthodontic camouflage but not orthognathic surgery because of the risks of skin bruising, poor healing and a temporomandibular disorder. A satisfactory dental appearance and occlusion were achieved after camouflage treatment with orthodontic anchor screws and the use of Class II elastics, including the preservation of the stomatognathic functions. Acceptable occlusion and dentition were maintained after a two-year retention period. This treatment strategy of orthodontic camouflage using temporary anchorage, such as anchor screws and Class II elastics, may be a viable treatment option for skeletal malocclusion patients with EDS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 The Optimal Prepregnancy Body Mass Index for Lactation in Japanese Women with Neonatal Separation as Analyzed by a Differential Equation 63 69 EN Katsuhiko Tada Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Yasunari Miyagi Miyake Ofuku Clinic Kazue Nakamura Department of Neonatology, National Hospital Organization, Okayama Medical Center Moe Yorozu Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Emi Fukushima Department of Nursing, National Hospital Organization, Okayama Medical Center Kazumasa Kumazawa Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Makoto Nakamura Department of Neonatology, National Hospital Organization, Okayama Medical Center Misao Kageyama Department of Neonatology, National Hospital Organization, Okayama Medical Center Original Article 10.18926/ATM/61436 We used a differential equation to identify the biological relationship between the maternal prepregnancy body mass index (BMI) and lactation on postpartum day 4 in Japanese women with neonatal separation. This retro-spective observational study included 252 mothers (135 primiparas, 117 multiparas) whose singleton neonates were admitted to a neonatal ICU. We formulated hypotheses based on breast anatomy to analyze the relation-ship between the expressed milk obtained on postpartum day 4 and the maternal prepregnancy BMI with the following differential equation: y’(x) = k y(x)/x, where k is the constant, x is the prepregnancy BMI, and y is the expressed milk volume. The formula was then obtained as y(x) = axk, where a is the constant. The Akaike information criterion (AIC) was used to estimate the regression equation with the maximum likelihood for primiparas and multiparas. The best criteria for BMI determined by the AIC were 20.89 kg/m2 in primiparas and 20.19 kg/m2 in multiparas. These were the optimal BMI values for lactation, coinciding with the median prepregnancy BMI in the study population (20.78 kg/m2 in primiparas and 20.06 kg/m2 in multiparas). The formula based on biomathematics might help establish the biological relationship between prepregnancy BMI and breastmilk volume. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer 15 23 EN Kuniaki Katsui Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ogata Department of Radiology, Iwakuni Clinical Center Akihiro Tada Department of Radiology, Okayama Diagnostic Imaging Center Soichi Sugiyama Department of Radiology, Okayama University Hospital Kotaro Yoshio Department of Radiology, Okayama University Hospital Masahiro Kuroda Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Katsuyuki Kiura Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/61429 The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants 557 562 EN Mikako Ishiguro Department of Internal Medicine, Tsuyama Chuo Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Kenichiro Ogura Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Akira Hiratsuka Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Hiromasa Takeda Department of Internal Medicine, Tsuyama Chuo Hospital Daisuke Kawai Department of Internal Medicine, Tsuyama Chuo Hospital Hirofumi Tsugeno Department of Internal Medicine, Tsuyama Chuo Hospital Shigeatsu Fujiki Department of Internal Medicine, Tsuyama Chuo Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61217 A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Soft Tissue Myoepithelioma of the Shoulder 531 535 EN Kazuhiko Hashimoto Department of Orthopedic Surgery, Kindai University Hospital Shunji Nishimura Department of Orthopedic Surgery, Kindai University Hospital Takaaki Chikugo Department of Pathology, Kindai University Hospital Ryosuke Kakinoki Department of Orthopedic Surgery, Kindai University Hospital Masao Akagi Department of Orthopedic Surgery, Kindai University Hospital Case Report 10.18926/AMO/61213 Soft tissue myoepitheliomas are often misdiagnosed due to their rarity. Herein, we describe a case of soft tissue myoepithelioma of the shoulder. A 72-year-old woman had a suspected sarcoma on her shoulder and under-went open biopsy. She was referred to our hospital, where the tumor was widely resected and the diagnosis of myoepithelioma was histologically confirmed. No recurrence has been observed in the 3 years since the sur-gery. Careful and prompt planning is necessary for the effective treatment of myoepithelioma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Potential of Artificial Intelligence for Estimating Japanese Fetal Weights 483 493 EN Yasunari Miyagi Medical Data Labo Takahito Miyake Department of Obstetrics and Gynecology, Miyake Clinic Original Article 10.18926/AMO/61207 We developed an artificial intelligence (AI) method for estimating fetal weights of Japanese fetuses based on the gestational weeks and the bi-parietal diameter, abdominal circumference, and femur length. The AI comprised of neural network architecture was trained by deep learning with a dataset that consists of ± 2 standard devia-tion (SD), ± 1.5SD, and ± 0SD categories of the approved standard values of ultrasonic measurements of the fetal weights of Japanese fetuses (Japan Society of Ultrasonics in Medicine [JSUM] data). We investigated the residuals and compared 2 other regression formulae for estimating the fetal weights of Japanese fetuses by t-test and Bland-Altman analyses, respectively. The residuals of the AI for the test dataset that was 12.5% of the JSUM data were 6.4 ± 2.6, −3.8 ± 8.6, and −0.32 ± 6.3 (g) at −2SD, +2SD, and all categories, respectively. The residu-als of another AI method created with all of the JSUM data, of which 20% were randomized validation data, were −1.5 ± 9.4, −2.5 ± 7.3, and −1.1 ± 6.7 (g) for −2SD, +2SD, and all categories, respectively. The residuals of this AI were not different from zero, whereas those of the published formulae differed from zero. Though vali-dation is required, the AI demonstrated potential for generating fetal weights accurately, especially for extreme fetal weights. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Reality of Gastric Cancer in Young Patients: The Importance and Difficulty of the Early Diagnosis, Prevention and Treatment 461 466 EN Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/61204 Gastric cancer usually arises in middle-aged to older patients, and is rarely found in younger patients. The clin-ical characteristics, etiology, prognosis, preventive methods and treatment of gastric cancer in young patients have not been fully investigated because of its low prevalence. In this review, we discuss the current under-standing and clinical problems associated with gastric cancer in young patients. Helicobacter pylori (H. pylori), which is a major cause of gastric cancer, especially in older populations, is closely associated with gastric cancer in young patients as well as in older patients. Gastric cancer in young patients tends to be diagnosed at an advanced stage with alarm symptoms. However, young patients with advanced gastric cancer tend to have a favorable general condition and organ function, so they can tolerate intensive systematic chemotherapy. Unfortunately, the prognosis of gastric cancer in young patients with an advanced stage is not favorable. We should not take this rare disease lightly, given its poor prognosis if patients are diagnosed at an unresectable stage. The evaluation of the H. pylori infection status and performance of H. pylori eradication therapy to prevent gastric cancer in young patients as well as the development of more intensive chemotherapy regimens for unre-sectable gastric cancer in young patients are warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Study Protocol for Assessing the Efficacy of Compression Therapy Using Stockings and Sleeves to Prevent Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients 455 459 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 Kengo Kanetaka 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 Clinical Study Protocol 10.18926/AMO/60808 Taxanes are key drugs for patients with breast cancer. A major adverse effect associated with the administration of the taxane docetaxel is chemotherapy-induced peripheral neuropathy (CIPN). We are conducting a singlecenter, single-arm, open-label historical control trial to evaluate the ability of compression therapy using stockings or sleeves to prevent CIPN due to docetaxel treatment. The primary endpoint is the incidence of all-grade CIPN according to patients’ records until 3 weeks after the fourth docetaxel administration. This study’s results will clarify whether compression therapy using stockings or sleeves can prevent CIPN in breast cancer patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms 407 413 EN Masaaki Togo Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Yuko Akazawa Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Taro Akashi Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Rika Yamashita Oral Care Center, Nagasaki University Hospital Izumi Yoshitomi JCHO Isahaya General Hospital Kazuo Ohba JCHO Isahaya General Hospital Satsuki Hashimoto JCHO Isahaya General Hospital Hiroko Iwashita JCHO Isahaya General Hospital Tadafumi Kurogi Oral Care Center, Nagasaki University Hospital Yukiko Osada Dental Hygienist's Office, Department of Medical Technology, Nagasaki University Hospital Noriko Wada Dental Hygienist's Office, Department of Medical Technology, Nagasaki University Hospital Yoshifumi Imamura Department of Respiratory Medicine, Nagasaki University Hospital Keiichi Hashiguchi Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Naoyuki Yamaguchi Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Hisayoshi Kondo Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medicine Kazuhiko Nakao Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Original Article 10.18926/AMO/60800 Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 The Late Phase/Early Phase Ratio of Pancreatic CT Values as a Novel Predictor of Pancreatic Fistula after Distal Pancreatectomy 351 358 EN Masashi Utsumi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takayuki Yabuki Department of Radiology, National Hospital Organization, Iwakuni Clinical Center Seiichi Nagahisa Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Seitaro Nishimura Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yuta Une Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yuji Kimura Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Megumi Watanabe Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takashi Arataa Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Koh Katsuda Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Kohji Tanakaya Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organization, Iwakuni Clinical Center Original Article 10.18926/AMO/60374 Post-operative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). In this retrospective study, we reviewed the data from patients who underwent DP between 2008 and 2019 in our institute to determine whether the late phase/early phase ratio (L/E ratio) by preoperative computed tomography (CT) scan in the pancreas could predict POPF occurrence after DP. We examined the relationship between preoperative or intraoperative factors and the occurrence of POPF after DP using statistical methods in 23 males and 21 females with a mean age of 73. The mean L/E ratio was significantly lower in the POPF group than the non-POPF group (p=0.035). The L/E ratio had moderate diagnostic accuracy, with a calculated optimal cutoff value of 0.77. In univariate analysis, a significant association was noted between POPF and stump thickness ≥ 16.9, body mass index ≥ 27.5, and L/E ratio ≤ 0.77. In the multivariate analysis, the L/E ratio (odds ratio, 5.96; p=0.036) was an independent risk factor for POPF. Our findings suggest that the pancreatic L/E ratio may predict the occurrence of POPF after DP. This measure may be useful in preoperative risk stratification, patient counseling, and perioperative patient management, improving clinical outcomes after DP. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Immobility-reducing Effects of Ketamine during the Forced Swim Test on 5-HT1A Receptor Activity in the Medial Prefrontal Cortex in an Intractable Depression Model 301 306 EN Kei Takahashi Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ushio 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/60368 Ketamine has been clinically proven to ameliorate depression, including treatment-resistant depression. The detailed mechanism of action of ketamine in treatment-resistant depression remains unclear. We examined the effects of ketamine on the immobility times of adrenocorticotropic hormone (ACTH)-treated rats during the forced swim test, and we explored the mechanism by which ketamine acts in this model. We investigated the neuroanatomical site of action by microinjecting ketamine into the medial prefrontal cortex of rats. A significant reduction of the rats’ immobility during the forced swim test was observed after the intraperitoneal injection of ketamine in both saline- and ACTH-treated rats. The microinjection of ketamine into the medial prefrontal cortex also decreased immobility during the forced swim test in both saline- and ACTH-treated rats. The immobility-decreasing effect of intraperitoneally injected ketamine was blocked by administering WAY100635, a 5-HT1A receptor antagonist, into the medial prefrontal cortex. These findings contribute to the evidence that ketamine can be useful against treatment-resistant depressive conditions. The immobility-reducing effects of ketamine might be mediated by 5-HT1A receptor activity in the medial prefrontal cortex. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1615-5262 20 2020 Additional kernel observer: privilege escalation attack prevention mechanism focusing on system call privilege changes 461 473 EN Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Yohei Akao Graduate School of Natural Science and Technology, Okayama University. NTT Communications Corporation Ryota Yoshitani raduate School of Natural Science and Technology, Okayama University Yuichi Nakamura Hitachi Ltd. Masaki Hashimoto Graduate School of Information Security, Institute of Information Security Cyberattacks, especially attacks that exploit operating system vulnerabilities, have been increasing in recent years. In particular, if administrator privileges are acquired by an attacker through a privilege escalation attack, the attacker can operate the entire system and cause serious damage. In this paper, we propose an additional kernel observer (AKO) that prevents privilege escalation attacks that exploit operating system vulnerabilities. We focus on the fact that a process privilege can be changed only by specific system calls. AKO monitors privilege information changes during system call processing. If AKO detects a privilege change after system call processing, whereby the invoked system call does not originally change the process privilege, AKO regards the change as a privilege escalation attack and applies countermeasures against it. AKO can therefore prevent privilege escalation attacks. Introducing the proposed method in advance can prevent this type of attack by changing any process privilege that was not originally changed in a system call, regardless of the vulnerability type. In this paper, we describe the design and implementation of AKO for Linux x86 64-bit. Moreover, we show that AKO can be expanded to prevent the falsification of various data in the kernel space. Then, we present an expansion example that prevents the invalidation of Security-Enhanced Linux. Finally, our evaluation results show that AKO is effective against privilege escalation attacks, while maintaining low overhead. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children 89 94 EN Akiko Kada Clinical Research Center, NHO Nagoya Medical Center Reiji Fukano Department of Pediatrics, Yamaguchi University Graduate School of Medicine Tetsuya Mori Department of Pediatrics, St. Marianna University School of Medicine Hospital Michi Kamei Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences Fumiko Tanaka Department of Pediatrics, Saiseikai Yokohamashi Nanbu Hospital Junichi Ueyama Department of Pediatrics, Tottori University Hospital, Masahiro Sekimizu Department of Pediatrics, NHO Nagoya Medical Center Tomoo Osumi Children’s Cancer Center, National Center for Child Health and Development Takeshi Mori Department of Hematology and Oncology, Children’s Cancer Center, Kobe Children’s Hospital Yuhki Koga Department of Pediatrics, Graduate School of Medical Sciences Kyushu University Kentaro Ohki Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development Naoto Fujita Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Tetsuo Mitsui Department of Pediatrics, Yamagata University Hospital Akiko M. Saito Clinical Research Center, NHO Nagoya Medical Center Hiroya Hashimoto Clinical Research Center, NHO Nagoya Medical Center Ryoji Kobayashi Department of Pediatrics and Adolescence, Sapporo Hokuyu Hospital Clinical Study Protocol 10.18926/AMO/57959 No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 The Prevalence and Characteristics of Older Japanese Adults with Polypharmacy, Based on Regionally Representative Health Insurance Claims Data 41 48 EN Hoichi Amano Graduate School of Public Health, Teikyo University Kenichi Fujimoto Graduate School of Public Health, Teikyo University Makoto Fujimori Graduate School of Public Health, Teikyo University Natsumi Saka Department of Orthopaedic Surgery, Teikyo University School of Medicine Kyoko Nomura Graduate School of Public Health, Teikyo University Shinichi Tanihara Graduate School of Public Health, Teikyo University Original Article 10.18926/AMO/57951 We aimed to clarify the prevalence of polypharmacy among elderly individuals in Japan. We used the data obtained from a large-scale population-based representative database of health insurance claims in a single prefecture in Japan. We examined all of the outpatient and pharmaceutical health insurance claims for National Health Insurance and those for Late-stage Elderly Health Insurance in Nagasaki Prefecture, Japan between April and June 2016. When two or more claim forms were issued for a patient in a single month, we combined the data and identified the number of prescribed drugs for each person. The definition of polypharmacy is a the prescription of six or more drugs per month. We investigated the prevalence of polypharmacy among the beneficiaries of the two insurance systems. Of the 605,406 beneficiaries of the 2 insurance systems, 121,033 (20.0%) patients with polypharmacy were identified. The prevalence of polypharmacy increased with age, especially among the beneficiaries aged > 85 years, with about half of the beneficiaries having polypharmacy status. About half of the people aged > 85 years in the database had polypharmacy status. When a drug is prescribed to an elderly individual, it is necessary to consider the possibility of polypharmacy-related problems. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 Minimally Invasive Surgery for Unstable Pelvic Ring Fractures: Transiliac Rod and Screw Fixation 27 32 EN Kazukiyo Toda Department of Orthopaedic Surgery, Kobe Red Cross Hospital Yukihisa Yagata Department of Orthopaedic Surgery, Hyogo Emergency Medical Center, Takeshi Kikuchi Department of Orthopaedic Surgery, Kobe Red Cross Hospital Tomoyuki Takigawa Department of Orthopaedic Surgery, Okayama University Hospital Yasuo Ito Department of Orthopaedic Surgery, Kobe Red Cross Hospital Original Article 10.18926/AMO/57949 Pelvic fractures occur with high-energy trauma, and the patient’s clinical status is unstable. Although a number of surgical methods for unstable pelvic fractures are available, none can achieve strong fixation with minimal invasiveness. We describe a surgical transiliac rod and screw fixation (TIF) procedure that provides minimally invasive fixation using a spinal implant for unstable pelvic ring fractures, and we retrospectively analyzed the procedure’s outcomes in 27 patients with type B or C1 fractures (based on the AO/ATO classification system). Small skin incisions are made above the posterior superior iliac spines on both sides. The ilium is partially resected, and two iliac screws are inserted on each side. The spinous process of the sacral spine is then shaved, and the iliac screws are connected to 2 rods, one placed caudal to the other. Corrective manipulation is performed at the fracture site, and the rods are connected with connectors. Favorable fracture reduction, defined as a rating of ‘excellent’ or ‘good,’ was achieved in 77.8% of the patients. Transiliac rod and screw fixation (TIF) will be a useful therapeutic option for unstable pelvic ring fractures. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 15250016 28 3 2020 Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody 794 804 EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Tsumura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Morihiro Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsushi Kubota Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Aoyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Mizuguchi Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University Yasuo Urata Oncolys BioPharma Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2019 地域在住の前期及び後期高齢者の食行動に影響する要因と栄養士の役割 EN Michiko Hashimoto Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 17599660 11 2018 Chromatographic paper-based analytical devices using an oxidized paper substrate 179 184 EN Yuki Hashimoto Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University A novel detection scheme using chromatographic retention was proposed for paper-based analytical devices (PADs). Using a wax printer and an ink-jet printer, the PADs consisted of a straight-flow channel, a circular sample zone, and a band of brilliant green (BG) printed at the connection between the sample zone and the flow channel. When a constant volume of a sample solution was applied to the sample zone, the BG band formed a colored bar along the flow channel that marked the adsorption and desorption of the paper substrate according to the principles of chromatography. If the sample solution contained an anionic complex of boric acid with chromotropic acid, the anionic complex enhanced desorption of the BG from the paper substrate via the formation of an ion-pair with the BG, which resulted in an elongated colored bar. Fundamental equations for the retention behavior of the BG on the PADs were derived using a model based on chromatographic principles and ion-pairing formation. A retardation factor, Rf, was correlated with the concentration of boric acid contained in the sample solutions. To enhance the adsorption of the BG, 2,2,6,6-tetramethylpiperidine 1-oxyl was used to oxidize the paper substrate. The oxidized paper substrate shortened the colored bar of a blank solution and formed a clear boundary for the color. When the analytical conditions were optimized for pH and the concentration of chromotropic acid, the PAD permitted the measurement of boric acid for a concentration ranging from 0.3 to 3 mM. The proposed model was validated when the fitting curve was calculated using the derived equations, which resulted in good agreement with the experimental data. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 Relationship between Sedentary Behavior and All-cause Mortality in Japanese Chronic Hemodialysis Patients: A Prospective Cohort Study 419 425 EN Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Nobuyuki Miyatake 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 Kiichi Koumoto Innoshima General Hospital Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Hiroo Hashimoto Innoshima General Hospital Original Article 10.18926/AMO/57372 We investigated the relationship between sedentary behavior and all-cause mortality in patients undergoing hemodialysis. A total of 71 patients (39 men, 32 women, aged 72.1±11.7 years) were enrolled in this longitudinal study. Their sedentary behavior was measured using a tri-accelerometer that provides relative values per daily wearing time. We classified the sedentary behavior time into 2 groups (under the median: short-sedentary behavior (SB) group; over the median: long-SB group) and compared the groups’ clinical parameters. We compared the groups’ survival rates by using Kaplan-Meier curves and the log-rank test, and we performed multivariate analyses by a Cox-proportional hazard model to evaluate the relationship between the sedentary behavior and the survival rate. Twenty patients (28.2%) died during the observation period. The survival rate of the short-SB group was significantly higher than that of the long-SB group. Sedentary behavior was thus an important factor for all-cause mortality even after adjusting for confounding factors by a Cox-proportional hazard model. Sedentary behavior is closely linked to all-cause mortality, especially total days and non-hemodialysis days, and reducing sedentary behavior may be beneficial to reduce the all-cause mortality of patients on chronic hemodialysis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 Risk Factors for Low Bone Mineral Density Determined in Patients in a General Practice Setting 403 411 EN Akemi Ando Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mitsugi Honda Division of Radiology, Department of Medical Technology, Okayama University Hospital Yoshihisa Hanayama 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 Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Kataoka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/57370 Osteoporosis increases the risk of bone fractures. It is diagnosed based on an individual’s bone mineral density (BMD) or a fracture without trauma. BMD is usually measured by the dual energy X-ray absorptiometry (DXA) method. Here we investigated factors for the earliest possible prediction of decreased BMD by examining the relationships between patients’ BMD values and changes in the patients’ physical and laboratory values. We retrospectively reviewed the medical records of 149 patients who visited our department in 2014-2015 for a variety of reasons and underwent an area BMD examination by DXA. We analyzed the relationships between decreasing BMD and the patients’ gender, age, body mass index (BMI), medical background, hemoglobin, electrolytes, and thyroid function. Thirty-nine of the patients were diagnosed with osteoporosis based on their T-scores. An adjusted analysis showed that female gender, aging, and increased serum calcium level were significantly related to decreasing femoral BMD, whereas high BMI was associated with an increase in femoral BMD. Collectively the results indicate that for the early detection of low BMD, it is important for general-practice physicians to consider conducting a BMD checkup when treating female and elderly patients with a low BMI and/or elevated serum calcium level. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 13882481 104 2019 Bipolar anodic electrochemical exfoliation of graphite powders 106475 EN Hideki Hashimoto Department of Applied Chemistry, School of Advanced Engineering, Kogakuin University Yusuke Muramatsu Department of Applied Chemistry, School of Advanced Engineering, Kogakuin University Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Hidetaka Asoh Department of Applied Chemistry, School of Advanced Engineering, Kogakuin University The electrochemical exfoliation of graphite has attracted considerable attention as a method for large-scale, rapid production of graphene and graphene oxide (GO). As exfoliation typically requires direct electrical contact, and is limited by the shape and/or size of the starting graphite, treatment of small graphite particles and powders, the typical form available commercially, is extremely difficult. In this study, GO nanosheets were successfully prepared from small graphite particles and powders by a bipolar electrochemical process. Graphite samples were placed between two platinum feeder electrodes, and a constant current was applied between the feeder electrodes using dilute sulfuric acid as the electrolyte. Optical microscopy, atomic force microscopy, X-ray diffractometry, Raman spectroscopy, and X-ray photoelectron spectroscopy were employed to examine the samples obtained after electrolysis. The results obtained from these analyses confirmed that anodic electrochemical exfoliation occurs in the graphite samples, and the exfoliated samples are basically highly crystalline GO nanosheets with a low degree of oxidation (C/O = 3.6–5.3). This simple electrochemical method is extremely useful for preparing large amounts of graphene and GO from small particles of graphite. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 2 15 2018 Outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation 1901 1903 EN Yoshihiro Inamoto National Cancer Center Hospital Tomohiro Matsuda National Cancer Center Hospital Ken Tabuchi Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Saiko Kurosawa National Cancer Center Hospital Hideki Nakasone Saitama Medical Center, Jichi Medical University Hisakazu Nishimori Okayama University Hospital Satoshi Yamasaki National Hospital Organization Kyushu Medical Center Noriko Doki Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Koji Iwato Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital Takehiko Mori Keio University School of Medicine Satoshi Takahashi The Institute of Medical Science, The University of Tokyo Hiromasa Yabe Tokai University Hospital, Akio Kohno JA Aichi Konan Kosei Hospital Hirohisa Nakamae Osaka City University Toru Sakura Saiseikai Maebashi Hospital Hisako Hashimoto Kobe City Medical Center General Hospital Junichi Sugita Hokkaido University Hospital Hiroatsu Ago Shimane Prefectural Central Hospital Takahiro Fukuda National Cancer Center Hospital Tatsuo Ichinohe Research Institute for Radiation Biology and Medicine, Hiroshima University Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Takuya Yamashita St. Luke's International Hospital Japan Society for Hematopoietic Cell Transplantation Late Effects and Quality of Life Working Group To characterize the outcomes of patients who developed a particular subsequent solid cancer after hematopoietic cell transplantation (HCT), age at cancer diagnosis, survival, and causes of death were compared with the respective primary cancer in the general population, using data from the national HCT registry and population-based cancer registries in Japan. Among 31 867 patients who underwent a first HCT between 1990 and 2013 and had progression-free survival at 1 year, 713 patients developed subsequent solid cancer. The median age at subsequent solid cancer diagnosis was 55 years, which was significantly younger than the 67 years for primary cancer patients in the general population (P < .001). The overall survival probability was 60% at 3 years after diagnosis of subsequent solid cancer and differed according to cancer type. Development of most solid cancers was associated with an increased risk of subsequent mortality after HCT. Subsequent solid cancers accounted for 76% of causes of death. Overall survival probabilities adjusted for age, sex, and year of diagnosis were lower in the HCT population than in the general population for colon, bone/soft tissue, and central nervous system cancers and did not differ statistically for other cancers. In conclusion, most subsequent solid cancers occurred at younger ages than primary cancers, emphasizing the need for cancer screening at younger ages. Subsequent solid cancers showed similar or worse survival compared with primary cancers. Biological and genetic differences between primary and subsequent solid cancers remain to be determined. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Evaluation of Treatment Response in Prostate Cancer and Renal Cell Carcinoma Patients Using 11C-choline PET/CT Findings 341 347 EN Kazuhiro Kitajima Department of Radiology, Division of Nuclear Medicine and PET Center, Hyogo College of Medicine Shingo Yamamoto Department of Urology, Hyogo College of Medicine Yukako Nakanishi Department of Urology, Hyogo College of Medicine Yusuke Yamada Department of Urology, Hyogo College of Medicine Takahiko Hashimoto Department of Urology, Hyogo College of Medicine Toru Suzuki Department of Urology, Hyogo College of Medicine Shuken Go Department of Urology, Hyogo College of Medicine Akihiro Kanematsu Department of Urology, Hyogo College of Medicine Michio Nojima Department of Urology, Hyogo College of Medicine Masayuki Fujiwara Department of Radiology, Hyogo College of Medicine Hayato Kaida Department of Radiology, Kindai University Faculty of Medicine Masakatsu Tsurusaki Department of Radiology, Kindai University Faculty of Medicine Tomonori Kanda Department of Radiology, Kobe University Graduate School of Medicine Yukihisa Tamaki Department of Radiation Oncology, Shimane University School of Medicine Koichiro Yamakado Department of Radiology, Hyogo College of Medicine Original Article 10.18926/AMO/56936 We investigated the effectiveness of 11C-choline-positron emission tomography/computed tomography (PET/CT) for evaluating treatment response in patients with prostate cancer or renal cell carcinoma. We performed 34 11C-choline PET/CT scans before/after a combined total of 17 courses of treatment in 6 patients with prostate cancer and 2 with renal cell carcinoma. The 17 treatments including hormonal therapy, radiotherapy, chemotherapy, radium-223, molecular target therapy, radiofrequency ablation, transcatheter arterial embolization, and cancer immunotherapy yielded 1 (5.9%) complete metabolic response (CMR), 3 (17.6%) partial metabolic responses (PMRs), 2 (11.8%) stable metabolic diseases (SMDs), and 11 (64.7%) progressive metabolic diseases (PMDs). Target lesions were observed in bone (n=14), lymph nodes (n=5), lung (n=2), prostate (n=2), and pleura (n=1), with CMR in 4, PMR in 10, SMD in 8 and PMD in 2 lesions. SUVmax values of the target lesions before and after treatment were 7.87±2.67 and 5.29±3.98, respectively, for a mean reduction of −35.4±43.6%. The response for the 8 prostate cancer-treatment courses was PMD, which correlated well with changes in serum prostatic specific antigen (PSA) (7 of 8 cases showed increased PSA). 11C-choline-PET/CT may be an effective tool for detecting viable residual tumors and evaluating treatment response in prostate cancer and renal cell carcinoma patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Dynamic Reorganization of Microtubule and Glioma Invasion 285 297 EN Yoshihiro Otani Department of Neurosurgery, The University of Texas Health Science Center at Houston Tomotsugu Ichikawa Department of Neurosurgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi 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 Review 10.18926/AMO/56930 Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion. No potential conflict of interest relevant to this article was reported.

岡山実験動物研究会 Acta Medica Okayama 35 2019 コモンマーモセットを育てる 26 28 EN Haruna Hashimoto Advanced Science Research Center, Okayama University In mid July 2018, the common marmoset bred in Okayama University gave birth to a triplet. It is very difficult to raise three infants. We selected the most heaviest one of her siblings, and we call her “POCKE”. We brought her up on the bottle for 80 days from the birth instead of her own mother. After 81 days, she finaly weand. Now she has become attached to human, but we hope that she gets back to their original community, as a “common” marmoset. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Middle or Lower Esophageal Cancer Using Elective Nodal Irradiation: Comparison with 3D Conformal Radiotherapy 247 257 EN Kotaro Yoshio Department of Radiology, Kagawa Prefectural Central Hospital Akihisa Wakita Division of Medical Physics, Euro MediTech Co. Ltd Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Takahiro Kitayama Department of Radiology, Kagawa Prefectural Central Hospital Kento Hisazumi Department of Radiology, Kagawa Prefectural Central Hospital Daisaku Inoue Department of Radiology, Kagawa Prefectural Central Hospital Nobuhisa Tajiri Department of Radiology, Kagawa Prefectural Central Hospital Tsuyoki Shiode Department of Radiology, Kagawa Prefectural Central Hospital Shiro Akaki Department of Radiology, Kagawa Prefectural Central Hospital Susumu Kanazawa Department of Radiology, Okayama University Hospital Original Article 10.18926/AMO/56868 We investigated the feasibility of simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) using elective nodal irradiation (ENI) for middle or lower esophageal cancer and compared it with three-dimensional conformal radiotherapy (3D-CRT). The study included 15 patients. The prescribed doses included a standard dose (50.4 Gy) and a high dose (60 Gy) for the planning target volume (PTV) of the involved lesions. The objective of the whole lung volume receiving ≥ 20 Gy (V20Gy) was < 30%, and the mean lung dose (MLD) was < 20 Gy. The volumes of the lung receiving 5 Gy (V5Gy) and the heart receiving 30-50 Gy (V30-50Gy) were kept as low as reasonably achievable. As a result, SIB-VMAT showed superior dose conformity for the PTV (p<0.001). Although the lung V5Gy was significantly increased (p<0.001), the V20Gy and MLD showed no significant increase. The heart V30-50Gy showed a > 20% reduction in the mean against 3D-CRTs. Our results demonstrate the feasibility of SIB-VMAT for the treatment of middle or lower esophageal cancer with ENI. Although attention should be paid to the low-dose area of the lungs, SIB-VMAT would be a promising treatment option with improved outcomes for esophageal cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Psychiatry 189 195 EN Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ko Tsutsui Department of Neuropsychiatry, Akita University Graduate School of Medicine Takashi Kanbayashi Department of Neuropsychiatry, Akita University Graduate School of Medicine Keiko Tanaka Department of Animal Model Development, Brain Research Institute, Niigata University Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56860 Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently-discovered autoimmune disorder in which antibodies target NMDAR in the brain. The number of reported cases of anti-NMDAR encephalitis has increased rapidly. Anti-NMDAR encephalitis can be mistakenly diagnosed as psychiatric disorders because many patients present with prominent psychiatric symptoms and visit psychiatric institutions first. Thus, psychiatrists should cultivate a better understanding of anti-NMDAR encephalitis. In this review, we present the mechanisms, epidemiology, symptoms and clinical course, diagnostic tests, treatment and outcomes of patients with anti-NMDAR encephalitis. Furthermore, we discuss the diversity of clinical spectra of anti-NMDAR encephalitis, and demonstrate a differential diagnosis of psychiatric disease from the perspective of psychiatry. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2019 スメグマ菌におけるメチオニン関連遺伝子欠損株作製とその解析 EN Kazuki Hashimoto 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 73 2 2019 Clinical Characteristics of Severe Refractory Asthma Associated with the Effectiveness of Bronchial Thermoplasty 155 160 EN Daisuke Minami Department of Respiratory Medicine, Okayama Medical Center Hiroe Kayatani Department of Respiratory Medicine, Okayama Medical Center Ken Sato Department of Respiratory Medicine, Okayama Medical Center Keiichi Fujiwara Department of Respiratory Medicine, Okayama Medical Center Takuo Shibayama Department of Respiratory Medicine, Okayama Medical Center Toshiro Yonei Department of Respiratory Medicine, Okayama Medical Center Toshio Sato Department of Respiratory Medicine, Okayama Medical Center Original Article 10.18926/AMO/56651 We investigated the clinical characteristics of refractory asthma associated with the effectiveness of bronchial thermoplasty (BT). We retrospectively evaluated data from 10 patients who underwent BT between June 2016 and December 2017 at Okayama Medical Center. The following were measured before and 6 months post-BT: forced expiratory volume in 1.0 s (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) level, blood eosinophil counts (Eosi), Asthma Quality of Life Questionnaire (AQLQ) score, and preventive medication use. At baseline, the mean post-bronchodilator FEV1 was 80.9% of the predicted value (range 45.6-115.7%). All patients were being treated with moderate- or high-dose inhaled corticosteroids and long-acting β2 agonists. The AQLQ improved from 4.26±1.67 at baseline to 5.59±0.94 at 6 months post-BT (p<0.05). The %FEV1, FeNO, IgE, and Eosi did not change significantly between baseline and 6 months post-BT. No severe complications were reported. BT was effective for non-allergic and non-eosinophilic in 3 patients, and allergic or eosinophilic in 4 patients. Their AQLQ improved by > 0.5 points post-BT. For both allergic and eosinophilic asthmatics following mepolizumab, BT was not useful. BT was effective for non-allergic and non-eosinophilic or allergic asthmatics, but insufficient for both allergic and eosinophilic following mepolizumab. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Conventional-dose Versus Half-dose Sulfamethoxazole-trimethoprim for the Prophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Disease: A Non-blind, Randomized Controlled Trial 85 89 EN Yoshiyuki Abe Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Kazutoshi Fujibayashi Medical Technology Innovation Center, Juntendo University Yuji Nishizaki Medical Technology Innovation Center, Juntendo University Naotake Yanagisawa Medical Technology Innovation Center, Juntendo University Shuko Nojiri Clinical Research and Trial Center, Juntendo University Hospital Soichiro Nakano Geriatric General Medicine, Juntendo Tokyo Koto Geriatric Medical Center Kurisu Tada Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Ken Yamaji Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Naoto Tamura Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Clinical Study Protocol 10.18926/AMO/56464 Pneumocystis pneumonia (PCP) due to Pneumocystis jirovecii infection is the leading cause of fatal opportunistic infections in immunocompromised patients. We will determine whether a daily sulfamethoxazole-trimethoprim (SMX/TMP) dose of 200/40 mg was non-inferior to 400/80 mg for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. This is a randomized, open-label, multicenter controlled trial. The primary outcome is the rate of PCP prevention at 52 weeks. The secondary outcome is the discontinuation rate of SMX/TMP. The trial will evaluate the optimal dose of SMX/TMP for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Impact of Body Mass Index of Japanese Gallbladder Cancer Patients on their Postoperative Outcomes 51 59 EN Masakuni Fujii Department of Internal Medicine, Okayama Saiseikai General Hospital Kenji Fujimoto Department of Public Health, University of Occupational and Environmental Health Syuntaro Yabe Department of Internal Medicine, Okayama Saiseikai General Hospital Junichiro Nasu Department of Internal Medicine, Okayama Saiseikai General Hospital Jiro Miyaike Department of Internal Medicine, Imabari Saiseikai General Hospital Masao Yoshioka Department of Internal Medicine, Okayama Saiseikai General Hospital Junji Shiode Department of Internal Medicine, Okayama Saiseikai General Hospital Kazuhide Yamamoto Department of Internal Medicine, Okayama Saiseikai General Hospital Shinya Matsuda Department of Public Health, University of Occupational and Environmental Health Original Article 10.18926/AMO/56458 　We investigated the relationship between body mass index (BMI) and postoperative outcomes in 450 gallbladder cancer patients in Japan. We collected patient information, including sex, age, underlying disease, BMI, stage, surgery method, postoperative time to discharge, and postoperative Medicare fees, from the Japanese administrative database associated with the Diagnosis Procedure Combination system. We classified patient BMIs as underweight (BMI<18.5 kg/m2), normal (BMI≥18.5 kg/m2 and <25 kg/m2) or overweight/obese (BMI≥25 kg/m2), then investigated the relationship between these categories and two postoperative outcomes: time to discharge and postoperative Medicare fees. The median postoperative time to discharge was 12 days in all patients, and 12 days in each of the three weight groups (p=0.62, n.s.). The median postoperative Medicare fees from surgery until discharge were (USD): all patients, $5,002; underweight, $5,875; normal weight, $4,797; and overweight/obese, $5,179 (p=0.146, n.s.). A multivariate analysis with adjustment for competing risk factors revealed that BMI was not associated with increased risk of longer postoperative time to discharge (normal weight: HR 1.17, p=0.29; overweight/obese: HR 1.17, p=0.37) or higher postoperative Medicare fees (OR 0.99, p=0.86, n.s.). Thus, high BMI was not found to be a factor for poor postoperative outcomes in Japanese patients with gallbladder cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 The Role of Kallikrein-Related Peptidases in Atopic Dermatitis 1 6 EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56452 Excessive protease activity is a characteristic abnormality that affects the epidermal barrier in patients with atopic dermatitis (AD). Kallikrein-related peptidases (KLKs) are excessively expressed in AD lesions, and it is suggested that the abnormal action of KLKs is involved in the skin barrier dysfunction in AD. In other words, overexpressed KLKs disrupt the normal barrier function, and due to that breakdown, external substances that can become antigens of AD easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines. Further investigations are required to elucidate the role of KLKs in AD; this knowledge could contribute to the design of new therapeutic and prophylactic drugs for AD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 6 2018 Salmonella Osteomyelitis of the Distal Tibia in a Healthy Woman 601 604 EN Kazuhiko Hashimoto Department of Orthopedic Surgery, Kindai University Hospital Shunji Nishimura Department of Orthopedic Surgery, Kindai University Hospital Shunki Iemura Department of Orthopedic Surgery, Kindai University Hospital Masao Akagi Department of Orthopedic Surgery, Kindai University Hospital Case Report 10.18926/AMO/56379 Salmonella osteomyelitis is extremely rare; only a few cases have been reported in healthy adults. We describe a case of salmonella osteomyelitis in an otherwise healthy 20-year-old Japanese woman who presented with distal tibial pain. X-ray and magnetic resonance imaging showed a lesion suspected to be a bone cyst. Osteomyelitis was diagnosed when pus was observed during an open biopsy. The bacterial culture examination yielded salmonella. Surgical drainage and antibiotic treatment were performed, after which no recurrence was observed. To our best knowledge, this is the first report of salmonella osteomyelitis of the distal tibia in an otherwise healthy individual. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 4 2018 An Open-label Single-arm Trial of a Novel Extramedullary Guide Coordinated with 3D Surgical Assistive Software for Total Knee Arthroplasty 441 445 EN Daihei Kida Department of Orthopedic Surgery and Rheumatology, Nagoya Medical Center Hiroya Hashimoto Clinical Research Center, Nagoya Medical Center Akiko M. Saito Clinical Research Center, Nagoya Medical Center Yukari Kito Arthro Design. Ltd Kouichi Mori Department of Orthopedic Surgery and Rheumatology, Nagoya Medical Center Kenya Terabe Department of Orthopedic Surgery and Rheumatology, Nagoya Medical Center Nobunori Takahashi Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine Yasushi Tomita Department of Cardiology, Nagoya Medical Center Clinical Study Protocol 10.18926/AMO/56186 There is no assistive device for extramedullary surgery coordinated with 3D surgical assistive software for the total knee arthroplasty (TKA). We developed a novel extramedullary universal guide coordinated with 3D surgical assistive software and a novel extramedullary patient-specific assistive guide for the placement of femoral components by referring to an area not affected by cartilage or bone spurs, and filed a patent application. In this study, we visualize and reconstruct the total alignment of the lower extremity in TKA using these surgical devices, and validate their precision. A report releasing study results will be submitted in an appropriate journal. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 4 2018 Mixed HCV Infection of Genotype 1B and Other Genotypes Influences Non-response during Daclatasvir + Asunaprevir Combination Therapy 401 406 EN Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fusao Ikeda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chizuru Mori Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Takaguchi Department of Internal Medicine, Kagawa Prefectural Central Hospital Shin-ichi Fujioka Department of Internal Medicine, Okayama Saiseikai General Hospital Haruhiko Kobashi Department of Internal Medicine, Okayama Red Cross Hospital Yoichi Morimoto Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Kazuya Kariyama Department of Liver Disease Center, Okayama City Hospital Kosaku Sakaguchi Department of Internal Medicine, Fukuyama City Hospital Noriaki Hashimoto Department of Internal Medicine, Mihara Red Cross Hospital Akio Moriya Department of Gastroenterology, Mitoyo General Hospital Mitsuhiko Kawaguchi Department of Internal Medicine, Kawaguchi Medical Clinic Hirokazu Miyatake Department of Internal Medicine, Hiroshima City Hospital Hiroaki Hagihara Department of Gastroenterology, Sumitomo Besshi Hospital Junichi Kubota Department of Internal Medicine, Tajiri Hospital Hiroki Takayama Department of Gastroenterology, Tsuyama Central Hospital Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yasunaka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Iwasaki Health Service Center, Okayama University Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56178 Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 4 2018 Relationship between Sedentary Behavior and Health-Related Quality of Life in Patients on Chronic Hemodialysis 395 400 EN Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Akihiko Katayama The Faculty of Social Studies, Shikokugakuin University Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Hiroo Hashimoto Innoshima General Hospital Original Article 10.18926/AMO/56177 We explored the relationship between sedentary behavior and the health-related quality of life (HRQOL) in patients on chronic hemodialysis. A total of 60 outpatients, aged 71.1±12.0 years, were enrolled in this cross-sectional study. Sedentary behavior was measured using a tri-accelerometer and HRQOL was evaluated by the Euro-QOL questionnaire (EQ-5D). The relationship between the patients’ sedentary behavior and HRQOL was evaluated by simple and multiple correlation analyses. The relative sedentary behavior (%) for total days was 73.7±12.9% and the EQ-5D scores were 0.688±0.233. Relative sedentary behavior (%) was negatively correlated with EQ-5D scores for total days, hemodialysis days and non-hemodialysis days. The relative light-intensity physical activity (LPA) (%) and relative moderately vigorous-intensity physical activity (MVPA) (%) were correlated with EQ-5D scores. Multiple regression showed that the relative sedentary behavior (%) had a clinical impact on EQ-5D scores after adjusting for confounding factors for total, hemodialysis and non-hemodialysis days. Sedentary behavior is closely linked to HRQOL, and reducing sedentary behavior may be beneficial to improve the HRQOL of patients on chronic hemodialysis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 3 2018 Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer 289 296 EN Kazuhiro Kitajima Division of Nuclear Medicine and PET Center, Hyogo College of Medicine Shingo Yamamoto Department of Urology, Hyogo College of Medicine Soichi Odawara Division of Nuclear Medicine and PET Center, Hyogo College of Medicine Kaoru Kobayashi Department of Radiology, Hyogo College of Medicine Masayuki Fujiwara Department of Radiology, Hyogo College of Medicine Norihiko Kamikonya Department of Radiology, Hyogo College of Medicine Kazuhito Fukushima Department of Nuclear Medicine, University Hospital Wuerzburg Yukako Nakanishi Department of Urology, Hyogo College of Medicine Takahiko Hashimoto Department of Urology, Hyogo College of Medicine Yusuke Yamada Department of Urology, Hyogo College of Medicine Toru Suzuki Department of Urology, Hyogo College of Medicine Akihiro Kanematsu Department of Urology, Hyogo College of Medicine Michio Nojima Department of Urology, Hyogo College of Medicine Koichiro Yamakado Department of Radiology, Hyogo College of Medicine Original Article 10.18926/AMO/56075 We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 3 2018 Renal Function after Nephrectomy Influences the Risk of Cardiovascular Events 241 247 EN Taiki Kambara Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Tanimoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Saika Department of Urology, Hiroshima City Hospital Hideaki Hashimoto Department of Urology, Okayama Central Hospital Tadashi Oeda Department of Urology, Onomichi Municipal Hospital Tomoyasu Tsushima Department of Urology, Okayama Medical Center Shunji Hayata Department of Urology, Tottori Municipal Hospital Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Okayama Urological Research Group Original Article 10.18926/AMO/56069 We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 2 2018 Formulae Based on Biomathematics to Estimate the Standard Value of Fetal Growth of Japanese 115 119 EN Yasunari Miyagi Department of Gynecology, Miyake Ofuku Clinic Katsuhiko Tada Department of Obstetrics and Gynecology, Okayama Medical Cente Riko Takayoshi Department of Obstetrics and Gynecology, Miyake Clinic Nobutsugu Oguni Department of Obstetrics and Gynecology, Miyake Clinic Yasushi Sato Department of Obstetrics and Gynecology, Miyake Clinic Maki Shibata Department of Obstetrics and Gynecology, Miyake Clinic Machiko Kiyokawa Department of Obstetrics and Gynecology, Miyake Clinic Tadashi Hashimoto Department of Obstetrics and Gynecology, Miyake Clinic Tomoyoshi Takada Department of Obstetrics and Gynecology, Miyake Clinic Takashi Oda Department of Obstetrics and Gynecology, Miyake Clinic Takahito Miyake Department of Obstetrics and Gynecology, Miyake Clinic Original Article 10.18926/AMO/55851 We devised biomathematics-based formulae to estimate the standard values of fetal growth of Japanese after 22 weeks' gestation. The growth rates of bi-parietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal body weight (EFBW) at the time of gestation were assumed to be proportional to the product of the value at the time and the rest value of an unknown maximum value, respectively. The EFBW was also assumed to follow a multiple logistic function of BPD, AC and FL to fit the standard values of Japanese fetuses published by the Japan Society of Ultrasonics in Medicine. The Mann-Whitney test was used for statistical analysis. The values as a function of gestational day, t, were as follows: BPD(t)=99.6/(1+exp (2.725−0.01837＊t)) (mm); AC(t)=39.7/(1+exp (2.454−0.01379＊t)) (cm); FL(t)=79.6/(1+exp (2.851−0.01710＊t)) (mm); EFBW(t)=8045.1/(1+exp (6.028−0.06582＊BPD(t)−0.1469＊AC(t)+ 0.07377＊FL(t))) (g). EFBW as a function of BPD, AC and FL was as follows: EFBW=8045.1/(1+exp (4.747+ 0.02584＊BPD+0.1010＊AC−0.1416＊FL)) (g). When the BPD, AC and FL were at −2 standard deviation (SD), −1SD, mean and + 2SD, the EFBW values calculated by the formula were statistically closer to the standard values than conventional formulas with p-values of 4.871×10−7, 4.228×10−7, 9.777×10−7 and 0.028, respectively. The formulae based on biomathematics might be useful to estimate the fetal growth standard values. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 3 2017 平成28年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 163 165 EN Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 6 2017 Disseminated Nontuberculous Mycobacterial Infection in a Patient with Anti-IFN-γ Autoantibodies 547 552 EN Masakuni Tanimizu Department of Internal Medicine, Tottori Municipal Hospital Kenji Mizuno Department of Surgery, Tottori Municipal Hospital Masayuki Hashimoto Department of Radiology, Tottori Municipal Hospital Case Report 10.18926/AMO/55594 We treated a 72-year-old Japanese female with sustained high fever and overall body exhaustion. An infectious liver cyst and right lung pneumonia were suspected causes. Hepatic cystectomy and various antibiotics did not resolve symptoms. Pneumonia exacerbation and ascitic fluid retention, left lumbar spinal osteomyelitis, and peri-gastric lymph node abscess penetrating the stomach were observed. Mycobacterium avium was identified in sputum, ascites, vertebral body abscess puncture specimen, and pus mucus secretion in the stomach. We diagnosed a disseminated nontuberculous mycobacterial infection. She seemed immunocompetent, without signs of AIDS or hematological malignancy. Serum anti-IFN-γ autoantibodies tested positive and were suspected to be involved in the illness onset. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0021-8693 484 2017 F-rationality of the ring of modular invariants 207 223 EN Mitsuyasu Hashimoto Department of Mathematics, Okayama University Using the description of the Frobenius limit of modules over the ring of invariants under an action of a finite group on a polynomial ring over a field of characteristic p>0 developed by Symonds and the author, we give a characterization of the ring of invariants with a positive dual F-signature. Combining this result and Kemper's result on depths of the ring of invariants under an action of a permutation group, we give an example of an F-rational, but non-F-regular ring of invariants under the action of a finite group. No potential conflict of interest relevant to this article was reported.

Cambridge University Press Acta Medica Okayama 0027-7630 226 2017 Canonical and n-canonical modules of a Noetherian algebra 165 203 EN Mitsuyasu Hashimoto Department of Mathematics, Okayama University We define canonical and -canonical modules of a module-finite algebra over a Noether commutative ring and study their basic properties. Using -canonical modules, we generalize a theorem on -syzygy by Araya and Iima which generalize a well-known theorem on syzygies by Evans and Griffith. Among others, we prove a noncommutative version of Aoyama’s theorem which states that a canonical module descends with respect to a flat local homomorphism. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0001-8708 305 2017 The asymptotic behavior of Frobenius direct images of rings of invariants 144 164 EN Mitsuyasu Hashimoto Department of Mathematics, Okayama University Peter Symondsb University of Manchester We define the Frobenius limit of a module over a ring of prime characteristic to be the limit of the normalized Frobenius direct images in a certain Grothendieck group. When a finite group acts on a polynomial ring, we calculate this limit for all the modules over the twisted group algebra that are free over the polynomial ring; we also calculate the Frobenius limit for the restriction of these to the ring of invariants. As an application, we generalize the description of the generalized F-signature of a ring of invariants by the second author and Nakajima to the modular case. No potential conflict of interest relevant to this article was reported.

Taylor & Francis Acta Medica Okayama 0092-7872 45 4 2016 Equivariant class group. II. Enriched descent theorem 1509 1532 EN Mitsuyasu Hashimoto Department of Mathematics, Okayama University We prove a version of Grothendieck’s descent theorem on an ‘enriched’ principal fiber bundle, a principal fiber bundle with an action of a larger group scheme. Using this, we prove the isomorphisms of the equivariant Picard and the class groups arising from such a principal fiber bundle. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 20452322 7 2017 Directional cell expansion requires NIMA-related kinase 6 (NEK6)-mediated cortical microtubule destabilization; 7826 EN Shogo Takatani Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Shinichiro Ozawa Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Noriyoshi Yagi Graduate School of Biological Science, Nara Institute of Science and Technology Takashi Hotta Graduate School of Biological Science, Nara Institute of Science and Technology Takashi Hashimoto Graduate School of Biological Science, Nara Institute of Science and Technology Yuichiro Takahashi Graduate School of Natural Science and Technology/Faculty of Science, Okayama University Taku Takahashi Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Hiroyasu Motose Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University 　Plant cortical microtubules align perpendicular to the growth axis to determine the direction of cell growth. However, it remains unclear how plant cells form well-organized cortical microtubule arrays in the absence of a centrosome. In this study, we investigated the functions of Arabidopsis NIMA-related kinase 6 (NEK6), which regulates microtubule organization during anisotropic cell expansion. Quantitative analysis of hypocotyl cell growth in the nek6-1 mutant demonstrated that NEK6 suppresses ectopic outgrowth and promotes cell elongation in different regions of the hypocotyl. Loss of NEK6 function led to excessive microtubule waving and distortion, implying that NEK6 suppresses the aberrant cortical microtubules. Live cell imaging showed that NEK6 localizes to the microtubule lattice and to the shrinking plus and minus ends of microtubules. In agreement with this observation, the induced overexpression of NEK6 reduced and disorganized cortical microtubules and suppressed cell elongation. Furthermore, we identified five phosphorylation sites in β-tubulin that serve as substrates for NEK6 in vitro. Alanine substitution of the phosphorylation site Thr166 promoted incorporation of mutant β-tubulin into microtubules. Taken together, these results suggest that NEK6 promotes directional cell growth through phosphorylation of β-tubulin and the resulting destabilization of cortical microtubules. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 2 2017 家族性大腸腺腫症術後20年後に小腸癌を発症した1例 111 114 EN Yuusaku Sugihara Department of Gastroenterology and Hepatology, Okayama University Hospital Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Hospital Keita Harada Department of Gastroenterological Surgery, Okayama University Hospital Shiho Takashima Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Takei Department of Gastroenterological Surgery, Okayama University Hospital Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Hospital Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiko Mori Division of Endoscopy, Okayama University Hospital Hiroyuki Kishimoto Division of Endoscopy, Okayama University Hospital Takeshi Nagasaka Division of Endoscopy, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital A 58-year-old Japanese man visited a local clinic for the evaluation of a stomachache. He was diagnosed with intestinal obstruction. His medical history included a proctocolectomy at the age of 38 years, due to familial adenomatous polyposis (FAP). He was referred to our institution, where he underwent a computed tomography examination and endoscopy of the small intestine. The pathological diagnosis was adenocarcinoma. No invasive or metastatic lesions were observed. Therefore, partial resection of the ileum with lymphadenectomy and reconstruction of the ileostomy were performed. Pathological examination revealed that the tumor was type 2, pT3 (SS) , pN1, pPM0, pDM0, pRM0, INFb, ly1, v1, pEX0, PN0. Twenty-nine days after the surgery, the patient was diagnosed with lung metastasis and he underwent lung radiofrequency ablation. We suggest that long-term follow-up is necessary for patients after surgery for FAP, because of the risk of malignant disease developing in other organs. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 2 2017 Klebsiella pneumoniae を起因菌とした後腹膜膿瘍からの 炎症波及により腹部大動脈破裂に至った一例 107 109 EN Kenji Yamazakia Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Sakakima Department of Internal Medicine, Fujinomiya City General Hospital Yuka Nagakura Department of Internal Medicine, Fujinomiya City General Hospital Hiroyuki Hashimoto Department of Internal Medicine, Fujinomiya City General Hospital Takeshi Tashiro Department of Internal Medicine, Fujinomiya City General Hospital Masashi Miwa Department of Internal Medicine, Fujinomiya City General Hospital Katsuhiko Yonemura Department of Internal Medicine, Fujinomiya City General Hospital An 80-year-old Japanese man was admitted to our hospital in April 2016 with an acute high-grade fever and back pain. A systemic contrast-enhanced computed tomography scan disclosed a retroperitoneal abscess around his aorta. The blood culture revealed Klebsiella pneumoniae. Antibiotics (Cefotaxime 1 g i.v. q 6 hours) were administered, but the patient's symptoms worsened. The abscess then ruptured the aorta. An emergency surgical repair was done, and the patient recovered. Invasive Klebsiella pneumoniae syndrome has been detected in southeast Asia over the past two decades, and here we describe a rare case of a retroperitoneal abscess caused by Klebsiella pneumoniae that ruptured the aorta. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2017 A new occlusal surface design for artificial posterior teeth to achieve high masticatory performance EN Yuki Hashimoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2017 直交配置型FIB-SEMを用いたコラーゲン細線維の三次元形態計測 EN Mana Hashimoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 7 2017 全学教職課程における「教職論」の取組 : 学習内容の確実な定着と教師としての実践的な資質・能力の育成を目指して 175 182 EN Shintaro Kobayashi Center for Teacher Education and Development, Okayama University Takuji Hashimoto Center for Teacher Education and Development, Okayama University Hiroshi Takahata Center for Teacher Education and Development, Okayama University Shuuichi Inada Center for Teacher Education and Development, Okayama University Tomotaka Mishima Center for Teacher Education and Development, Okayama University Kayoko Soda Former Center for Teacher Education and Development, Okayama University Eiji Egi Former Center for Teacher Education and Development, Okayama University 10.18926/CTED/54942 　全学教職コア・カリキュラムの入門科目に位置付けられている「教職論」の授業については，継続的にその内容や手法に関して改善が図られてきた。平成28 年度についても，過去５年間の取組の成果を踏まえながら，特に次の４つの視点から改善内容を模索し，より実践的で参加型の授業になるように工夫をした。�@全学で導入された「60 分授業・4 学期制」に対応し，その利点を生かす。�Aワークシートの活用により，個々の受講生が個人で思考する時間を確保する。�Bペア学習・グループ学習の時間を設定し，可能な限りアクティブ・ラーニングを導入する。�C様々な課題の解決を目指して学校現場で実際に行われている取組を出来るだけ多く紹介する。これらの改善により，学習意欲の向上と学習内容の確実な定着を図った。その結果，受講終了時に実施したアンケート調査では，多くの受講生から授業の意義について肯定的な評価が得られた。 No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 7 2017 全学教職課程における「教職実践演習の取組」 : 60分授業・４学期制を柱に体系的に学べる講義づくりを目指して 81 90 EN Shuuichi Inada Center for Teacher Education and Development, Okayama University Hiroshi Takahata Center for Teacher Education and Development, Okayama University Tomotaka Mishima Center for Teacher Education and Development, Okayama University Seitaro Kobayashi Center for Teacher Education and Development, Okayama University Takuji Hashimoto Center for Teacher Education and Development, Okayama University Yasuyoshi Imai Center for Teacher Education and Development, Okayama University Masaru Kaga Graduate School of Education,Okayama University Fumio Yamane Former Center for Teacher Education and Development,Okayama University Kayoko Soda Former Center for Teacher Education and Development,Okayama University Eiji Egi Former Center for Teacher Education and Development,Okayama University Daisuke Goto Kawasaki University of Medical Welfare Shigenobu Takatsuka Center for Teacher Education and Development, Okayama University 10.18926/CTED/54933 　岡山大学における全学教職実践演習については，平成25年度の本格実施から，7課程認定学部（独自で開講する教育学部を除く）と教師教育開発センターが協働して取り組んでいる。平成28年度から岡山大学では，国立の総合大学全学部実施としては全国初となる「60分授業・4学期制」が導入された。この教育改革では，単純に現状の講義内容をそのまま詰め込むものではなく，教育方法・指導の改善を一層進め，体系的に学べる構造にする講義づくりが求められている。そこで，最初に学生の進路状況や取得見込みの教員免許状の現状を確認した。次に，教育実践力を構成する力がバランスよく形成されているか，４年生前半期に取り組んだ教育実習と全学教職実践演習後のアンケート結果をもとにその効果を検証した。これに基づいて，平成28年度以降の「60分授業・4学期制」に対応した内容を構築した。 No potential conflict of interest relevant to this article was reported.

Department of Mathematics, Faculty of Science, Okayama University Acta Medica Okayama 0030-1566 59 1 2017 Higher-dimensional absolute versions of symmetric, Frobenius, and quasi-Frobenius algebras 131 140 EN Mitsuyasu Hashimoto Department of Mathematics Faculty of Science, Okayama University 10.18926/mjou/54719 In this paper, we define and discuss higher-dimensional and absolute versions of symmetric, Frobenius, and quasi-Frobenius algebras. In particular, we compare these with the relative notions defined by Scheja and Storch. We also prove the validity of codimension two-argument for modules over a coherent sheaf of algebras with a 2-canonical module, generalizing a result of the author. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 3 2016 平成27年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 179 182 EN Kunitoshi Shigeyasu Baylor University Medical Center No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 5 2016 Relationship between Changes in Physical Activity and Changes in Health-related Quality of Life in Patients on Chronic Hemodialysis with 1-Year Follow-up 353 361 EN Akihiko Katayama Department of Hygiene, Faculty of Medicine, Kagawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Kazuhiro Ujike Innoshima General Hospital Hiroo Hashimoto Innoshima General Hospital Risa Kurato Department of Hygiene, Faculty of Medicine, Kagawa University Kiichi Koumoto Innoshima General Hospital Original Articles 10.18926/AMO/54593 In a longitudinal study, we examined the link between changes in physical activity and changes in health-related quality of life (HRQOL) in patients on chronic hemodialysis. Seventy-one patients (43 males, 28 females; aged 70.9±10.6 years) on chronic hemodialysis in September 2013 were enrolled. The data of the 43 patients whose complete measurements were taken again in September 2014 were used for the longitudinal analysis. Clinical parameters including age, height, dry weight, duration of hemodialysis, blood pressure (BP), blood triglyceride and HDL cholesterol levels, physical activity, and HRQOL were evaluated. Physical activity was measured by a tri-accelerometer, and HRQOL was evaluated by the EuroQol questionnaire (EQ-5D). In the first cross-sectional analysis, EQ-5D scores were significantly correlated with daily step counts (steps per day) on all days and non-hemodialysis days. In the second longitudinal analysis, in the women, changes in EQ-5D scores were positively correlated with changes in daily step counts on all days. In all patients, changes in EQ-5D were weakly and negatively correlated with changes in physical activity (1-3 METs: min per day) on hemodialysis days. Promoting daily physical activity may improve the HRQOL in patients on chronic hemodialysis, especially in women. No potential conflict of interest relevant to this article was reported.

ACADEMIC PRESS INC ELSEVIER SCIENCE Acta Medica Okayama 0021-8693 459 2016 Equivariant class group. I. Finite generation of the Picard and the class groups of an invariant subring 76 108 EN Mitsuyasu Hashimoto Okayama University The purpose of this paper is to define equivariant class group of a locally Krull scheme (that is, a scheme which is locally a prime spectrum of a Krull domain) with an action of a flat group scheme, study its basic properties, and apply it to prove the finite generation of the class group of an invariant subring. In particular, we prove the following. Let k be a field, G a smooth k-group scheme of finite type, and X a quasi-compact quasi-separated locally Krull G-scheme. Assume that there is a k-scheme Z of finite type and a dominant k -morphism Z→XZ→X. Let φ:X→Yφ:X→Y be a G -invariant morphism such that OY→(φ⁎OX)GOY→(φ⁎OX)G is an isomorphism. Then Y is locally Krull. If, moreover, Cl(X)Cl(X) is finitely generated, then Cl(G,X)Cl(G,X) and Cl(Y)Cl(Y) are also finitely generated, where Cl(G,X)Cl(G,X) is the equivariant class group. In fact, Cl(Y)Cl(Y) is a subquotient of Cl(G,X)Cl(G,X). For actions of connected group schemes on affine schemes, there are similar results of Magid and Waterhouse, but our result also holds for disconnected G. The proof depends on a similar result on (equivariant) Picard groups. No potential conflict of interest relevant to this article was reported.

Springer Singapore Acta Medica Okayama 0251-4184 40 3 2015 Classification of the Linearly Reductive Finite Subgroup Schemes of SL2 527 534 EN Mitsuyasu Hashimoto Department of Mathematics, Okayama University We classify the linearly reductive finite subgroup schemes G of SL2=SL(V) over an algebraically closed field k of positive characteristic, up to conjugation. As a corollary, we prove that such G is in one-to-one correspondence with an isomorphism class of two-dimensional F-rational Gorenstein complete local rings with the coefficient field k by the correspondence G↦((SymV)G) ˆ. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 アディポカイン「バスピン」の同定とメタボリックシンドロームにおける意義 103 109 EN Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 平成27年度岡山医学会賞 総合研究奨励賞（結城賞） 87 89 EN Akihiro Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 1 2016 薬物相互作用 (35―オピオイド鎮痛薬の薬物相互作用） 53 59 EN Hikaru Sada Makoto Kajizono Yoshihisa Kitamura Toshiaki Sendo No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 1 2016 回盲部潰瘍穿孔，食道潰瘍穿孔をきたした腸管Behçet 病の1 手術例 27 32 EN Yuta Tsukumo Kazuyuki Kawamoto Kosei Takagi Kai Chin Yuri Matsuba Yoshio Nagahisa Michio Okabe Yasuhiro Shirakawa Tadashi Itoh Toshiyoshi Fujiwara 　A 36-year-old Japanese man known to have incomplete Behçet’s disease (oral aphthous ulcers, genital ulcers, skin lesions, and esophageal and ileocecal ulcers) was admitted to our hospital in January 2011 for abdominal pain. We administered corticosteroids and immunosuppressants. Two months later, we performed an ileocecal resection to control gastrointestinal bleeding from the ileocecal ulcers. High fever persisted after this surgery, and upper gastrointestinal endoscopy demonstrated ulcer penetration between the lower and abdominal esophagus. Eighteen days after the initial ileocecal resection, we performed a lower esophagus resection, gastric tube reconstruction and enterostomy, during which we confirmed a 5-mm-dia. perforated site at the posterior wall of the abdominal esophagus. Postoperative anastomotic leakage and empyema occurred, but they were relieved by thoracic drainage and empyema dissection. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 1 2016 原発性十二指腸粘液癌の一例― 本邦報告16例の検討― 21 25 EN Ikumi Hamano Yusuke Matsumoto Yoshikatsu Endo Naoki Watanabe Kyouhei Kai Shizou Sato Yoji Wani 　Primary mucinous adenocarcinoma of the duodenum is rare. Here we report a case we recently encountered, and we review 16 cases reported in Japan. An 82-year-old Japanese woman was admitted to our hospital complaining of abdominal pain and heartburn. An endoscopic examination revealed a Type 2 tumor in the descending limb of the duodenum, and endoscopically obtained specimens revealed a poorly differentiated adenocarcinoma. We performed a curative pancreatoduodenectomy with lymph node resection, and the surgical specimen revealed that the duodenum was the primary site of the mucinous adenocarcinoma. The patient is currently alive ＞ 1 year after the operation without any evidence of recurrence. Of the 16 patients reviewed, all patients had advanced tumors those depth were T3-T4. 9 patients had lymph node metastasis and 4 patients had peritoneal dissemination at the time of surgery. Since mucinous adenocarcinoma of the duodenum is often progressive cancer at a diagnosis, which is tend to have a worse prognosis than other histological types. No potential conflict of interest relevant to this article was reported.

Elsevier Ireland Ltd. Acta Medica Okayama 0300-9572 85 12 2014 Feasibility study of immediate pharyngeal cooling initiation in cardiac arrest patients after arrival at the emergency room 1647 1653 EN Yoshimasa Takeda Takahisa Kawashima Kazuya Kiyota Shigeto Oda Naoki Morimoto Hitoshi Kobata Hisashi Isobe Mitsuru Honda Satoshi Fujimi Jun Onda Seishi I Tetsuya Sakamoto Masami Ishikawa Hiroshi Nakano Daikai Sadamitsu Masanobu Kishikawa Kosaku Kinoshita Tomoharu Yokoyama Masahiro Harada Michio Kitaura Kiyoshi Ichihara Hiroshi Hashimoto Hidekazu Tsuji Takashi Yorifuji Osamu Nagano Hiroshi Katayama Yoshihito Ujike Kiyoshi Morita AIM: Cooling the pharynx and upper oesophagus would be more advantageous for rapid induction of therapeutic hypothermia since the carotid arteries run in their vicinity. The aim of this study was to determine the effects of pharyngeal cooling on brain temperature and the safety and feasibility for patients under resuscitation. METHODS: Witnessed non-traumatic cardiac arrest patients (n=108) were randomized to receive standard care with (n=53) or without pharyngeal cooling (n=55). In the emergency room, pharyngeal cooling was initiated before or shortly after return of spontaneous circulation by perfusing physiological saline (5 °C) into a pharyngeal cuff for 120 min. RESULTS: There was a significant decrease in tympanic temperature at 40 min after arrival (P=0.02) with a maximum difference between the groups at 120 min (32.9 ± 1.2°C, pharyngeal cooling group vs. 34.1 ± 1.3°C, control group; P<0.001). The return of spontaneous circulation (70% vs. 65%, P=0.63) and rearrest (38% vs. 47%, P=0.45) rates were not significantly different based on the initiation of pharyngeal cooling. No post-treatment mechanical or cold-related injury was observed on the pharyngeal epithelium by macroscopic observation. The thrombocytopaenia incidence was lower in the pharyngeal cooling group (P=0.001) during the 3-day period after arrival. The cumulative survival rate at 1 month was not significantly different between the two groups. CONCLUSIONS: Initiation of pharyngeal cooling before or immediately after the return of spontaneous circulation is safe and feasible. Pharyngeal cooling can rapidly decrease tympanic temperature without adverse effects on circulation or the pharyngeal epithelium. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 平成26年度岡山医学会賞 総合研究奨励賞（結城賞） 175 178 EN Noboru Asada No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 5 2015 Abscisic acid induces ectopic outgrowth in epidermal cells through cortical microtubule reorganization in Arabidopsis thaliana 11364 EN Shogo Takatani Takashi Hirayama Takashi Hashimoto Taku Takahashi Hiroyasu Motose Abscisic acid (ABA) regulates seed maturation, germination and various stress responses in plants. The roles of ABA in cellular growth and morphogenesis, however, remain to be explored. Here, we report that ABA induces the ectopic outgrowth of epidermal cells in Arabidopsis thaliana. Seedlings of A. thaliana germinated and grown in the presence of ABA developed ectopic protrusions in the epidermal cells of hypocotyls, petioles and cotyledons. One protrusion was formed in the middle of each epidermal cell. In the hypocotyl epidermis, two types of cell files are arranged alternately into non-stoma cell files and stoma cell files, ectopic protrusions being restricted to the non-stoma cell files. This suggests the presence of a difference in the degree of sensitivity to ABA or in the capacity of cells to form protrusions between the two cell files. The ectopic outgrowth was suppressed in ABA insensitive mutants, whereas it was enhanced in ABA hypersensitive mutants. Interestingly, ABA-induced ectopic outgrowth was also suppressed in mutants in which microtubule organization was compromised. Furthermore, cortical microtubules were disorganized and depolymerized by the ABA treatment. These results suggest that ABA signaling induces ectopic outgrowth in epidermal cells through microtubule reorganization. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 4 2015 Effectiveness of Extending Treatment Duration in Therapy with Pegylated Interferon and Ribavirin for Genotype 2 Hepatitis C Virus Infection 237 244 EN Shintarou Nanba Fusao Ikeda Shin-ichi Fujioka Yasuyuki Araki Kouichi Takaguchi Noriaki Hashimoto Hiroyuki Seki Akinobu Takaki Yoshiaki Iwasaki Kazuhide Yamamoto Original Article 10.18926/AMO/53560 The effectiveness of extending treatment duration as response guided therapy was previously reported for chronic hepatitis C (CHC) genotype 1, but is still controversial for genotype 2. The present study is a retrospective cohort study to investigate the effectiveness of extending treatment duration in therapy with pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing on the timing at which patients obtained undetectable HCV RNA. A total of 306 patients who obtained undetectable HCV RNA by week 24 of treatment and completed 24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard therapy was achieved by 122 patients (51ｵ), and 89ｵ of them obtained sustained virological response (SVR), while 69ｵ of non-RVR patients achieved SVR. Non-RVR patients with undetectable HCV RNA at week 8, and insufficient adherence＜80ｵ pegylated interferon and ribavirin during the first 24 weeks, significantly improved their SVR rate by extended therapy. Among patients receiving extended therapy, drug adherences did not differ between SVR and non-SVR patients, indicating that extending treatment duration might compensate for insufficient antiviral effects due to insufficient drug adherences. This finding might be useful in creating a guideline for extending treatment duration for patients with CHC genotype 2. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 4 2015 Reactivity of CA19-9 and CA125 in Histological Subtypes of Epithelial Ovarian Tumors and Ovarian Endometriosis 227 235 EN Naohisa Nakagawa Hiromi Koda Noriko Nitta Yukie Nakahara Jiro Uno Toru Hashimoto Takashi Nakahori Masaaki Hasegawa Mikio Kataoka Original Article 10.18926/AMO/53559 Previous reports have shown that some ovarian endometrioid adenocarcinomas and ovarian clear cell adenocarcinomas derive from ovarian endometriosis (OE), and that endocervical-like mucinous borderline ovarian tumors are associated with OE. We examined the relationship between the staging and histological subtypes of OE or epithelial ovarian tumors (EOT) and the serum levels of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) to evaluate the potential of these markers for preoperative diagnosis. First, we analyzed the preoperative serum levels of CA19-9 and CA125 in 195 patients who were histopathologically diagnosed with OE or EOT. We then performed a case-control study in which 308 women were enrolled, the 195 women described above and 113 healthy women as control subjects. Serum CA19-9 and CA125 levels were found to be useful in differentiating between OE and serous adenocarcinoma, but not between OE and other EOT. Moreover, serum CA19-9 levels were useful for preoperative assessment between OE and stage I mucinous borderline ovarian tumors, with or without the interstitial infiltration. In addition, considering that the serum CA19-9 levels in stage I mucinous borderline ovarian tumors were elevated via the interstitial infiltration of leukocytes and that precancerous lesions are associated with a cancerous glycosylation disorder in the process of inflammatory carcinogenesis, the CA19-9 level may be considered a suitable biomarker for estimating drug susceptibility. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 陽子線治療 155 157 EN Kuniaki Katsui Tomoaki Okimoto Susumu Kanazawa No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 慢性移植片対宿主病に対するタミバロテン（AM80G）の医師主導臨床第�U相試験 133 137 EN Hisakazu Nishimori Yoshinobu Maeda No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 腹膜透析Update 111 115 EN Hitoshi Sugiyama No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 平成26年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 91 94 EN Shuya Yano No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 1 2015 家族性大腸腺腫症（FAP）に合併した同時性５多発大腸癌に対してリンパ節郭清を伴う腹腔鏡下大腸全摘術を施行した１例 25 29 EN Hiroshi Kato Masahiro Oishi Masahito Kodera Masao Yamamura Hideaki Ikeda Kenji Mizuno Yutaka Yamashita 　A 49-year-old Japanese man visited our hospital with chief complaints of difficulty with and bleeding during defecation. After a detailed examination, he was diagnosed with familial adenomatous polyposis (FAP) with multiple (five) colorectal cancers. The tumors were located in the right-sided, left-sided, and sigmoid colon, and the lower rectum. Regional lymph node involvement was observed, but no metastasis to other organs was detected. We, therefore, performed a laparoscopic total colectomy with superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) lymph node dissection. We were able to perform minimally invasive and cosmetically acceptable surgery using laparoscopy instead of highly-invasive open abdominal surgery. Our search of the literature revealed no reported cases of laparoscopic total colectomy with lymph node dissection for FAP with multiple colorectal cancers, making the present case the first to be reported in the literature. No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 5 2015 小中高一貫有権者教育プログラム開発の方法（１）:「選挙」をテーマとする小学校社会科の単元の開発を通して 93 100 EN Toshinori Kuwabara Bunzo Kudo Kenji Tanahashi Reio Yatabe Shigeki Koyama Kotaro Yoshimura Susumu Oshihara Tadamichi Nagata Yasuhiro Hashimoto Tatsuya Watanabe 10.18926/CTED/53239 　本研究は，市民社会に寄与し得る有権者の育成を目指し，児童・生徒の発達段階に応じた有権者教育のあり方 を追究して，小学校から高等学校までの12 年間を一貫する原理にもとづいた有権者教育プログラム開発のため の原理と方法を解明しようとするものである。そのために，第一に，子どもたちの政治に対する認識調査を行い， 子どもたちが政治的な概念についてどのような認識を持っており，それを教育によってどの程度まで変容させる ことができるかを明らかにした。そして，第二に，その調査の結果と従来の政治教育研究の成果をふまえて，有 権者教育のための小中高一貫カリキュラム・フレームワークを提示した。それに基づいて，第三に，具体的な単 元開発を行った。単元は，「選挙」，「議会」，「税金」という政治学の基本的概念をテーマとして取り上げて開発 したが，本稿では「選挙」概念をテーマとして開発した小学校社会科の単元を紹介する。 No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1525-0016 2014 Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer EN Satoru Kikuchi Hiroyuki Kishimoto Hiroshi Tazawa Yuuri Hashimoto Shinji Kuroda Masahiko Nishizaki Takeshi Nagasaka Yasuhiro Shirakawa Shunsuke Kagawa Yasuo Urata Robert M Hoffman Toshiyoshi Fujiwara Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2014 Fluorescence virus-guided capturing system of human colorectal circulating tumour cells for non-invasive companion diagnostics EN Kunitoshi Shigeyasu Hiroshi Tazawa Yuuri Hashimoto Yoshiko Mori Masahiko Nishizaki Hiroyuki Kishimoto Takeshi Nagasaka Shinji Kuroda Yasuo Urata Ajay Goel Shunsuke Kagawa Toshiyoshi Fujiwara Background Molecular-based companion diagnostic tests are being used with increasing frequency to predict their clinical response to various drugs, particularly for molecularly targeted drugs. However, invasive procedures are typically required to obtain tissues for this analysis. Circulating tumour cells (CTCs) are novel biomarkers that can be used for the prediction of disease progression and are also important surrogate sources of cancer cells. Because current CTC detection strategies mainly depend on epithelial cell-surface markers, the presence of heterogeneous populations of CTCs with epithelial and/or mesenchymal characteristics may pose obstacles to the detection of CTCs. Methods We developed a new approach to capture live CTCs among millions of peripheral blood leukocytes using a green fluorescent protein (GFP)-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401, TelomeScan). Results Our biological capturing system can image epithelial and mesenchymal tumour cells with telomerase activities as GFP-positive cells. After sorting, direct sequencing or mutation-specific PCR can precisely detect different mutations in KRAS, BRAF and KIT genes in epithelial, mesenchymal or epithelial–mesenchymal transition-induced CTCs, and in clinical blood samples from patients with colorectal cancer. Conclusions This fluorescence virus-guided viable CTC capturing method provides a non-invasive alternative to tissue biopsy or surgical resection of primary tumours for companion diagnostics. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 3 2014 膣後壁合併切除を伴う会陰アプローチが有用であった直腸巨大GISTの１切除例 217 221 EN Kazuhide Iwakawa Manabu Nishie Naoyuki Tokunaga Hideaki Miyaso Hiromi Iwagaki We report a case of giant rectal gastrointestinal stromal tumor (GIST) successfully resected by abdominoperineal resection combined with posterior vaginal wall resection. Our patient was a 79-year-old woman had been diagnosed as having von Recklinghausen disease at the age of 30 years. In 2006, a computed tomography (CT) scan revealed a tumor originating from the posterior wall of the rectum. In June 2010, she was admitted to our hospital with the chief complaint of bloody stool. A CT scan revealed a giant tumor that had increased to 9cm in size. Colonoscopy demonstrated a submucosal tumor, which was subsequently diagnosed by biopsy as a GIST. Due to the patient's continuous bleeding and abdominal pain, an emergent abdominoperineal resection was performed at that time. The tumor, which measured 8×9cm, was immunohistochemically positive for c-kit and CD34. Concomitant resection of the posterior wall of the vagina via the perineal approach provided a wide area to expose the tumor for a safe operation. The patient has been well with no sign of recurrence since the operation. This procedure is recommended as a useful approach for giant rectal GISTs or rectal cancer with invasion of the posterior pelvic wall. No potential conflict of interest relevant to this article was reported.

安全工学会 Acta Medica Okayama 0570-4480 53 5 2014 安全教育のため手の甲によるバルブ速度測定画像認識法 295 302 EN Hirotsugu MINOWA Yoshiomi MUNESAWA Kohei HASHIMOTO 　人的要因の事故を防止する為，仮想現実感を利用した訓練の実現が期待されている．仮想環境での訓練の利点は実環境に近い環境で訓練できる点にある．しかし，プラント内で基本操作であるバルブの操作をシステムへ伝えるユーザ・インタフェース（UIと省略）は現在なく，実環境に即した訓練ができない問題がある． 　そこで本研究では，仮想環境におけるバルブ開操作訓練を実現するバルブ操作UI開発のため，バルブの丸ハンドルの回転速度を測定する画像認識手法を提案する．本手法はバルブの丸ハンドルを回す手から取得した光学的自然特徴点を利用する．本バルブ開操作UIはPC，Webカメラといった一般的な製品を用い平易に実現できる利点がある． 　本手法は，評価実験で22.5-90deg/sを測定できる事を確認できたため，発火危険を想定したバルブ操作訓練のためのUIに適用できる事が明らかとなった． No potential conflict of interest relevant to this article was reported.