American Society for Clinical InvestigationActa Medica Okayama2379-370810242025Enhancement of drug delivery through fibroblast activation protein–targeted near-infrared photoimmunotherapye195776ENSeitaroNishimuraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTasukuMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYasushigeTakedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTatsuyaTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHijiriMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceMasaakiAkaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTerukiKobayashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencePeter L.ChoykeMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIHHisatakaKobayashiMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIHToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceThe tumor microenvironment plays a key role in cancer progression and therapy resistance, with cancer-associated fibroblasts (CAFs) contributing to desmoplasia, extracellular matrix (ECM) remodeling, and elevated interstitial fluid pressure, all of which hinder drug delivery. We investigated fibroblast activation protein–targeted (FAP-targeted) near-infrared photoimmunotherapy (NIR-PIT) as a strategy to improve drug penetration in CAF-rich tumors. In clinical esophageal cancer samples, FAP expression strongly correlated with increased collagen I, hyaluronic acid, and microvascular collapse. CAF-rich 3D spheroids demonstrated elevated ECM deposition and significantly impaired drug uptake compared with CAF-poor models. FAP-targeted NIR-PIT selectively reduced CAFs, reduced ECM components, and restored drug permeability. In vivo, FAP-targeted NIR-PIT enhanced the accumulation of panitumumab and Abraxane in CAF-rich tumors and improved antitumor efficacy when combined with chemotherapy. These findings highlight FAP-targeted NIR-PIT as a promising therapeutic approach to remodel the tumor stroma and overcome drug resistance in desmoplastic solid tumors.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669417202025Tertiary Lymphoid Structures Are Associated with Favorable Clinical Outcomes and Negatively Correlated with Cancer-Associated Fibroblasts in Esophageal Cancer3351ENTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroNomaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeitaroNishimuraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasushigeTakedaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHijiriMatsumotoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuyaTakahashiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKentoKawasakiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasaakiAkaiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoakiMaedaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoruKikuchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeTanabeDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiTazawaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuhiroShirakawaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+ B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2072-664316242024Association Between Change in Prognostic Nutritional Index During Neoadjuvant Therapy and Dental Occlusal Support in Patients with Esophageal Cancer Under Neoadjuvant Therapy: A Retrospective Longitudinal Pilot Study4383ENReikoYamanaka-KohnoDepartment of Preventive Dentistry, Division of Dentistry, Okayama University HospitalYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamiInoue-MinakuchiDepartment of Oral Rehabilitation and Regenerative Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAyaYokoiDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuMoritaDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaisukeEkuniDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: A high prognostic nutritional index (PNI) is associated with good prognosis in patients with esophageal cancer. However, nutritional status often decreases during neoadjuvant therapy. Functional tooth units (FTUs) provide an index for the status of posterior occlusal support. We have previously reported that low PNI is related to low FTUs. Objectives: The purpose of this study was to retrospectively examine whether the status of occlusal support relates to changes in PNI during neoadjuvant therapy in patients with esophageal cancer. Methods: This study included 34 patients who underwent neoadjuvant therapy before esophagectomy (32 men, 2 women; age, 36-82 years) in 2012 at Okayama University Hospital. Patients were divided into the good occlusal support group (FTUs >= 11, n = 18) or poor occlusal support group (FTUs < 11, n = 16), and changes in PNI during neoadjuvant therapy were investigated. Results: PNI decreased significantly after neoadjuvant therapy, particularly in the good occlusal support group, and became more dispersed after neoadjuvant therapy. Decreases in PNI after neoadjuvant therapy showed a significant positive correlation with good occlusal support by multiple regression analysis (p = 0.03). The proportions of patients provided with nutritional intervention (p = 0.02) or early dental intervention (p = 0.04) were lower in the good occlusal support group than in the poor occlusal support group. Conclusions: Even in patients with esophageal cancer with good occlusal support experienced significant declines in PNI during neoadjuvant therapy, potentially due to delayed nutritional and dental interventions. Early multidisciplinary interventions are thus recommended for all patients, regardless of preoperative dental or nutritional status.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama2198-77931012024Gastro-tracheal fistula following esophageal cancer surgery through the retrosternal route: a case report252ENSeitaroNishimuraDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazuhiroNomaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKentoKawasakiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasashiHashimotoDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakuyaKatoDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNaoakiMaedaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunsukeTanabeDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasuhiroShirakawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground 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.Nature PortfolioActa Medica Okayama2045-23221412024Perioperative gum-chewing training prevents a decrease in tongue pressure after esophagectomy in thoracic esophageal cancer patients: a nonrandomized trial23886ENReikoYamanaka-KohnoDepartment of Preventive Dentistry, Division of Dentistry, Okayama University HospitalYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceAyaYokoiDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKazuyoshiShimizuDepartment of Anesthesiology and Resuscitology, Okayama University HospitalToshiharuMituhashiCenter for Innovative Clinical Medicine, Okayama University HospitalYoshihideNakamuraDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSoutoNanbaDental Clinic, Kurashiki Medical Check-Up CenterYurikaUchidaDepartment of Preventive Dentistry, Division of Dentistry, Okayama University HospitalTakayukiMaruyamaDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityManabuMoritaDepartment of Oral Health Sciences, Takarazuka University of Medical and Health CareDaisukeEkuniDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTongue pressure (TP) decreases significantly after esophagectomy in esophageal cancer patients (ECPs). Meanwhile, 2 weeks of gum-chewing training (GCT) significantly increased TP in healthy university students. We examined whether perioperative GCT would decrease the proportion of patients exhibiting a decline in TP at 2 weeks postoperatively, and prevent postoperative complications, in thoracic ECPs (TECPs). This was a single-center interventional study, and nonrandomized study with a historical control group (HCG). TECPs who underwent first-stage radical esophagectomy were recruited. Thirty-two patients of 40 in the gum-chewing group (GCG) were completed perioperative GCT in 3 times daily. Propensity score matching was performed with covariates related to TP including preoperative age, sex, body mass index, and the repetitive saliva swallowing test result, and yielded a matched cohort of 25 case pairs. Eleven GCG patients [44.0%] exhibited significantly lower TP at 2 weeks postoperatively than before esophagectomy was significantly fewer than that of 19 patients [76.0%] in the HCG. The median number of fever days (> 38 degrees C) in the 2 weeks after esophagectomy in the GCG was significantly fewer than those in the HCG. Perioperative GCT may prevent postoperative TP decline and postoperative dysphagia-related complications after esophagectomy.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama2198-77931012024Subtotal esophagectomy and concurrent reconstruction with free jejunal flap for primary esophageal cancer after pancreatoduodenectomy128ENKazuyaMoriwakeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTasukuMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground 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.Springer Science and Business Media LLCActa Medica Okayama0340-700472112023PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer37873802ENKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushigeTakedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHijiriMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeitaroNishimuraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaakiAkaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTerukiKobayashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813522023令和４年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞）5860ENYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama2198-7793912023Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report119ENTasukuMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaMoriwakeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground 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.Nature PortfolioActa Medica Okayama2045-23221212022Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment20152ENHiroakiSatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaakiAkaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTerukiKobayashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruNarusakaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKomotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiKatsuraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisatakaKobayashiMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, BethesdaToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama2198-7793812022Verrucous carcinoma of the esophagus with complete response after chemoradiotherapy128ENMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiSakuramaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground : 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.The Japanese Society of Internal MedicineActa Medica Okayama0918-29186182022Clinicopathological Characteristics of Superficial Barrett's Adenocarcinoma in a Japanese Population: A Retrospective, Multicenter Study11151123ENKentaHamadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromitsuKanzakiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiMiyaharaDepartment of Internal Medicine, Hiroshima City HospitalMasahiroNakagawaDepartment of Internal Medicine, Hiroshima City HospitalHirokazuMouriDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalMotowoMizunoDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalSakumaTakahashiDepartment of Gastroenterology, Kagawa Prefectural Central HospitalShinichiroHoriDepartment of Endoscopy, National Hospital Organization Shikoku Cancer CenterJunichiroNasuDepartment of Internal Medicine, Okayama Saiseikai General HospitalTakaoTsuzukiDepartment of Internal Medicine, Japanese Red Cross Society Himeji HospitalJiroMiyaikeDepartment of Internal Medicine, Saiseikai Imabari HospitalRyutaTakenakaDepartment of Internal Medicine, Tsuyama Chuo HospitalKenjiYamauchiDepartment of Gastroenterology, Mitoyo General HospitalSayoKobayashiDepartment of Internal Medicine, Fukuyama City HospitalTatsuyaToyokawaDepartment of Gastroenterology, National Hospital Organization Fukuyama Medical CenterMasafumiInoueDepartment of Gastroenterology, Japanese Red Cross Okayama HospitalMamoruNishimuraDepartment of Internal Medicine, Okayama City HospitalMinoruMatsubaraDepartment of Internal Medicine, Sumitomo Besshi HospitalJunTomodaDepartment of Internal Medicine, Akaiwa Medical Association HospitalYasushiYamasakiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama Gut Study GroupObjective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations. <br>
Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER). <br>
Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 <br>
Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 mu m experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005). <br>
Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0959-80491532021Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (Telomelysin) with radiotherapy in oesophageal cancer patients unfit for standard treatments98108ENYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiKoujimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKuniakiKatsuiDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuKanazawaDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoUrataOncolys BioPharma, Inc.ToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments.<br>
<br>
Methods: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy.<br>
<br>
Results: Of the 13 patients, 7, 3 and 3 patients were treated with 10(10), 10(11) and 10(12) virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8 thorn cells and increased PD-L1 expression.<br>
<br>
Conclusion: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments. (C) 2021 Elsevier Ltd. All rights reserved.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2196-3002622019Recent Changes and Improvements in Multidisciplinary Perioperative Management From a Nutritional Perspective: Dental Specialty Should Be Considered Important7075ENYoshihikoSogaDivison of Hospital Dentistry, Okayama University HospitalYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakakoAshiwaDivision of Nursing, Okayama University HospitalHiroshiMorimatsuPerioperative Management Center, Okayama University Hospital,Purpose of review<br>
Recently, multidisciplinary strategies on accelerated recovery postoperatively have been provided, and management of the perioperative period has changed and improved dramatically. We summarize the enhanced recovery after surgery (ERAS®) protocol and its outcomes from a nutritional perspective. We established the perioperative management center (PERiO), much of whose work contents conform to ERAS®, but intensive dental staff involvement is characteristic. We also summarize its outcomes.<br>
<br>
Recent findings<br>
ERAS® is a multimodal perioperative care pathway designed to achieve early recovery for patients undergoing a major surgery. Nutrition is a key pillar for patient-care. Throughout the perioperative period, oral nutrition is suggested as well as possible. Good outcomes have been reported by a meta-analysis of randomized controlled trials. However, dental staff are not regarded as part of the professional team. PERiO reported good outcomes of care bundles and suggested the importance of dental staff contribution. The Japanese social insurance system began to cover involvements of dental staff for perioperative oral management since 2012. Analysis of the nationwide administrative claims database in Japan concluded that preoperative oral care by a dentist significantly reduced postoperative complications in patients undergoing cancer surgery.<br>
<br>
Summary<br>
Currently, dental staff are not regarded as key professionals of ERAS®, although dental staff can contribute to good outcomes in the perioperative period and PERiO, and consequently the Japanese universal health insurance coverage system covering involvements of dental staff for perioperative oral management showed good outcomes. Therefore, further clinical studies involving the dental specialty should be considered important for perioperative management from nutritional perspectives.No potential conflict of interest relevant to this article was reported.Nature ResearchActa Medica Okayama2045-23221112021Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer1693ENRyoichiKatsubeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTerukiKobayashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiKomotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroakiSatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHisatakaKobayashiMolecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of HealthToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama1612-90591812020Association of dental occlusal support with the Prognostic Nutritional Index in patients with esophageal cancer who underwent esophagectomy4955ENReikoYamanaka-KohnoDivision of Hospital Dentistry, Central Clinical Department, Okayama University HospitalYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamiInoue-MinakuchiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyaYokoiDepartment of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMisatoMuroDivision of Hospital Dentistry, Central Clinical Department, Okayama University HospitalHirotakaKosakiDivision of Hospital Dentistry, Central Clinical Department, Okayama University HospitalShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuMoritaDepartment of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground</br>
The Prognostic Nutritional Index is useful for predicting surgical risk and overall survival based on preoperative immunological and nutritional status in patients undergoing digestive organ cancer surgery. The purpose of this study was to examine the association between the Prognostic Nutritional Index and dental status in patients with esophageal cancer who underwent esophagectomy.</br>
Methods</br>
This retrospective case–control study included 73 patients who underwent resection of esophageal cancer (69 males, 4 females; age 36–83). General and dental status were evaluated. The Prognostic Nutritional Index was calculated based on the serum albumin concentration and the total lymphocyte count, and subjects were divided into two groups based on index scores: a higher group, characterized by scores ≥ 45 (n = 54); and a lower group, characterized by scores < 45 (n = 19). Univariate analysis and multiple logistic regression analyses were used to compare between groups.</br>
Results</br>
Total protein, C-reactive protein, the number of sound and total decayed, missing and filled teeth, and the rate of patients with poor dental occlusal support showed significant differences between the lower and higher Prognostic Nutritional Index groups (p < 0.05). Stepwise logistic regression analysis by backward selection approach showed that low total protein, few sound teeth, and poor status of dental occlusal support were significantly associated with the lower Prognostic Nutritional Index (p = 0.007, 0.042, and 0.009, respectively).</br>
Conclusion</br>
Dental status, especially dental occlusal support and the number of sound teeth, showed a positive relationship with the Prognostic Nutritional Index in esophageal cancer patients who underwent esophagectomy.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812922017POEM (Per-Oral Endoscopic Myotomy) を施行した 食道アカラシアの1例115121ENYuusakuSugiharaDepartment of Gastroenterology and Hepatology, Okayama University HospitalKeitaHaradaDivision of Endoscopy, Okayama University HospitalRyoKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKenjiYamauchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalShihoTakashimaDepartment of Gastroenterology and Hepatology, Okayama University HospitalDaisukeTakeiDivision of Endoscopy, Okayama University HospitalToshihiroInokuchiaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Okayama University HospitalSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University HospitalSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University HospitalShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University HospitalKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University HospitalYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University HospitalNoriakiManabeDepartment of Clinical Pathology and Laboratory Medicine, Kawasaki Medical SchoolHaruhiroInoueDigestive Diseases Center, Showa University Koto Toyosu HospitalHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Hospital Esophageal achalasia is a disorder of the lower esophageal sphincter muscle. Patients present with dysphagia, chest pain, vomiting, and aspiration. Esophageal achalasia had traditionally been treated with esophageal achalasia balloon dilatation and the Heller-Dor method, but in recent years, the use of per-oral endoscopic myotomy (POEM) has increased. Our patient, a 39-yr-old male, began experiencing dysphagia 4 years prior to his referral to our hospital. Based on the results of esophagogastroduodenoscopy, esophageal radiography and high-resolution manometry, we made the diagnosis of esophageal achalasia (Chicago classification type I) . After informed consent from the patient and his family and approval from our hospital's ethics committee were obtained, we performed a POEM. The patient was discharged on the 4th day post-surgery. At the 1-year post-operative examination, no worsening of symptoms and no relapse were observed. POEM is an excellent treatment method for esophageal achalasia from the perspective of therapeutic effect and prevention of invasion. We recommend that it be considered as the first-choice treatment for achalasia. However, accessibility to the procedure itself is limited due to the few adequately trained operators worldwide. POEM should thus be performed by an expert operator at a high-volume center.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7122017Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer127133ENYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical SciencesKuniakiKatsuiDepartment of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorihisaKatayamaDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuKanazawaDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/54981Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581291201740年経過した食道アカラシア術後の食道拡張・下部食道狭窄症に 対して胸腔鏡下食道亜全摘が著効した1例4144ENYukiKatsuraDepartment of Gastroenterological Surgery, Okayama University HospitalYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University HospitalShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University HospitalNaomiMaedaDepartment of Gastroenterological Surgery, Okayama University HospitalKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Hospital When planning surgery for achalasia, it is important to plan for adequate myotomy and prevention of reflux. However, achalasia may recur if the procedure was inadequate or in patients with a long-term course. The present case is a 68-year-old woman who underwent myotomy of the lower esophageal sphincter 40 years ago, but recently reported difficulty in swallowing. Dilatation of the thoracic esophagus and stenosis of the abdominal esophagus were identified by examination, and the patient was diagnosed with recurrence of achalasia. After percutaneous endoscopic gastrostomy was performed to recover nutritional status, thoracoscopic esophagectomy was carried out. The patient'spost-operative course was uneventful and oral intake was enabled. At the time of writing, there has been no re-recurrence. There is no standard therapy for post-operative recurrence of achalasia. We believe that thoracoscopic esophagectomy for the recurrence of achalasia is a safe and minimally invasive alternative to conventional surgery.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812832016集学的治療により長期生存が得られた食道神経内分泌癌の2 例207212ENTatsuhiroGotodaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesYoshiyasuKonoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesKouMiuraDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesHiromitsuKanzakiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesYoshiroKawaharaDepartment of Endoscopy, Okayama University HospitalTakehiroTanakaDepartment of Pathology, , Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, , Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesYasuhiroShirakawadDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesMasahiroTabataDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesMitsuneTanimotoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Esophageal neuroendocrine carcinoma （ECC） is rare and has a poor prognosis when presenting with vascular invasion and distant metastasis from an early stage. Multidisciplinary therapy with surgery, chemotherapy, and radiation therapy may prolong survival in patients with advanced ECC, but there is as yet no standard therapy for advanced ECC. We treated two patients who have achieved long-term survival （＞ 4 years） who underwent multidisciplinary therapy, including chemotherapy, for ECC. Our experience with these two cases suggests that multidisciplinary therapy, including chemotherapy, may be effective for treating ECC at an advanced stage.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7032016Recurrence after Endoscopic Curative Resection of Mucosal Gastric Cancer Associated with an Adjacent Neoplastic Precursor Lesion213216ENSatoruKikuchiDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsushiKubotaDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaKuwadaDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuyaKagawaDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroShirakawaDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahikoNishizakiDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/54421A 69-year-old man underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) at the lesser curvature in the angle of stomach. Histological examination revealed tub1, pM, ly0, v0, pLM(-), pVM(-), and the resection was considered curative. The scar after ESD was followed by esophagogastroduodenoscopy (EGD) and biopsy. Twenty months later, EGD showed an ulcerative lesion in the vicinity of the ESD scar, and histological examination of the biopsy specimen showed adenocarcinoma. A distal gastrectomy with lymph node dissection was then performed. Postoperative pathology showed tub1, pM, pN0, ly0, v0, and Stage 1A. Skip lesions were seen in the specimen resected by ESD, and the histological review confirmed so-called “dysplasia-like atypia” (DLA) between the lesions. It has been reported recently that in DLA, the dysplasia-like change involves only the bases of the pits, without upper pit or surface epithelium involvement, and it is said that the rate of DLA is higher in gastric cancer patients. We speculated that a precancerous lesion close to the resected cancer developed into a local recurrence.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6932015Prone-Position Thoracoscopic Ligation of the Thoracic Duct for Chyle Leak Following Radical Neck Dissection in a Patient with a Right Aortic Arch173176ENYasuhiroShirakawaKazuhiroNomaToshiakiOharaHajimeKashimaNaoakiMaedaShunsukeTanabeShunsukeKagawaToshiyoshiFujiwaraCase Report10.18926/AMO/53524A chyle leak can occur as a complication after neck or chest surgery. Such a leak prolongs the hospital stay and is sometimes life-threatening. The treatment options are conservative management, interventional radiologic embolization, and surgery. Thoracoscopic ligation of the thoracic duct has emerged as a promising and definitive treatment. The case of a 65-year-old Japanese male patient with a rare congenital right aortic arch (typeVB1 of Edwardʼs classification) and a severe chyle leak that occurred after a total pharyngolaryngo-esophagectomy (TPLE) is described. The chyle leak was successfully managed by thoracoscopic ligation of the thoracic duct via a left-side approach with the patient in the prone position.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1525-00162014Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal CancerENSatoruKikuchiHiroyukiKishimotoHiroshiTazawaYuuriHashimotoShinjiKurodaMasahikoNishizakiTakeshiNagasakaYasuhiroShirakawaShunsukeKagawaYasuoUrataRobert M HoffmanToshiyoshiFujiwaraCurrently, 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.Academic Press Inc Elsevier ScienceActa Medica Okayama0022-480417822012Jejunal interposition reconstruction with a stomach preserving esophagectomy improves postoperative weight loss and reflux symptoms for esophageal cancer patients700707ENEijiYamadaYasuhiroShirakawaTomokiYamatsujiLeonSakumaMunenoriTakaokaTakakoYamadaKazuhiroNomaKazufumiSakuramaYasuhiroFujiwaraShunsukeTanabeTakeshiNagasakaToshiyoshiFujiwaraYoshioNaomotoBackground: Conventional reconstruction after an esophagectomy uses a gastric tube, which commonly causes several postoperative complaints such as gastric acid reflux in long-term survival cases. Intestinal interposition between the remnant esophagus and the stomach is an option to reduce complaints, and in this study, the advantages of jejunal interposition reconstruction with a stomach preserving esophagectomy (SPE) were assessed.
Materials and methods: Eleven cases of jejunal interposition with an SPE and 16 cases with gastric tube reconstruction as a control were subject to a comparison of operation time, amount of bleeding, postoperative quality of life, and endoscopic findings.
Results: The SPE group had a longer operation time (SPE: 560 +/- 121 min, control 414 +/- 83 min, P = 0.038), whereas there was no significant difference in blood loss. Postoperative weight loss was significantly recovered in the SPE group (SPE versus control = 94.0 +/- 5.4% versus 87.5 +/- 4.7% at 3 mo, P = 0.017; 97.2 +/- 7.5% versus 85.0 +/- 5.2% at 6 mo, P = 0.010), and there was a significant decrease in the occurrence of reflux symptoms such as heartburn, odynophagia, and cough when jejunal interposition with an SPE was done. Furthermore, reflux esophagitis and Barrett's epithelium were found in six out of 12 cases (50%) of the control group by postoperative endoscopy, while no cases in the SPE group had either condition (P < 0.01).
Conclusions: This reconstruction method is a promising option to improve postoperative quality of life, mainly due to the long-term elimination of reflux esophagitis, which assists in the recovery of postoperative weight loss.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1078-043219232013A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stem-like Cells in S/G(2)/M Phases64956505ENShuyaYanoHiroshiTazawaYuuriHashimotoYasuhiroShirakawaShinjiKurodaMasahikoNishizakiHiroyukiKishimotoFutoshiUnoTakeshiNagasakaYasuoUrataShunsukeKagawaRobert M.HoffmanToshiyoshiFujiwaraPurpose: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem-like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem-like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem-like cells.
Experimental Design: We established CD133(+) cancer stem-like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem-like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem-like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI).
Results: CD133(+) gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133(+) cancer stem-like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G(0)-G(1) to S/G(2)/M phases and subsequent cell death in quiescent CD133(+) cancer stem-like cells by mobilizing cell-cycle-related proteins. FUCCI enabled visualization of quiescent CD133(+) cancer stem-like cells and proliferating CD133(-) non-cancer stem-like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133(+) cancer stem-like cells maintained stemness by remaining in G(0)-G(1) phase. We showed that OBP-301 mobilized quiescent cancer stem-like cells in tumor spheres and xenografts into S/G(2)/M phases where they lost viability and cancer stem-like cell properties and became chemosensitive.
Conclusion: Oncolytic adenoviralinfection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem-like cells.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6822014Assistant-Based Standardization of Prone Position Thoracoscopic Esophagectomy111117ENYasuhiroShirakawaKazuhiroNomaNaoakiMaedaRyoichiKatsubeShunsukeTanabeToshiakiOharaKazufumiSakuramaToshiyoshiFujiwaraOriginal Article10.18926/AMO/52407Thoracoscopic esophagectomy in the prone position (TEPP) might enable solo-surgery in cases requiring resection of the esophagus and the surrounding lymph nodes due to the associated advantages of good exposure of the surgical field and ergonomic considerations for the surgeon. However, no one approach can be for all patients requiring extensive lymphadenectomy. We recently developed an assistant-based procedure to standardize exposure of the surgical field. Patients were divided into 1 of 2 groups:a pre-standardization group (n＝37) and a post-standardization group (n＝28). The thoracoscopic operative time was significantly shorter (p＝0.0037) in the post-standardization group (n＝28;
267±31min) than in the pre-standardization group (n＝37;301±53min). Further, learning curve analysis using the moving average method showed stabilization of the thoracoscopic operative time after the standardization. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the 2 groups. There were also no significant differences in the complication rate. Assistant-based surgery and standardization of the procedure resulted in a well-exposed and safe surgical field. TEPP decreased the operative time, even in patients requiring extensive lymphadenectomy.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0195-67018542013Multicentred surgical site infection surveillance using partitioning analysis282288ENY.FujiwaraT.YamadaY.NaomotoT.YamatsujiY.ShirakawaS.TanabeK.NomaT.KimuraH.AokiH.MatsukawaM.KimuraY.NonakaH.SasakiT.OnodaY.OtawaM.TakaokaT.FukazawaY.OhnoT.FujiwaraBackground: Surgical site infection (SSI) is an ongoing major public health problem throughout the world that increases healthcare costs. Utilizing a methodology that can help clinicians to continuously collect data about SSIs, analyse it and implement the feedback into routine hospital practice has been identified as a top national priority in Japan.
Aim: To conduct an intervention study through 'operations research' using partitioning at multiple facilities, and to reduce the incidence and consequences of SSI.
Methods: The Setouchi SSI Surveillance Group, which consists of seven institutes, started SSI surveillance in 2006. Until May of 2008, there were four surveillance periods (A-D). In all, 3089 patients underwent gastrointestinal surgery and were followed up for 30 days after their operations. Twenty-six factors that have been reported to be related to SSI were evaluated for all patients. The top three factors from each surveillance period were determined and then actual practice improvements were planned for each subsequent period.
Findings: The total SSI occurrence was 6.9% for period A, 6.3% for period B, 6.4% for period C and 3.9% for period D. Comparing periods A and D, there was a statistical significance in the decrease of SSI occurrence (P = 0.012).
Conclusion: Using the results and partitioning analysis of active SSI surveillance to contribute to action plans for improving clinical practice was effective in significantly reducing SSIs.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014食道原発悪性黒色腫の１切除例4548ENNaoakiMaedaYasuhiroShirakawaTakeshiKoujimaToshiakiOharaShunsukeTanabeKazuhiroNomaKazuhumiSakuramaToshiyosiFujiwara We report the case of a 61-old-man with a primary malignant melanoma of the esophagus, an extremely rare and highly aggressive malignancy. He presented with dysphagia, and we performed an upper gastrointestinal endoscopy that detected a tumor in the thoracic part of the esophagus. The biopsy showed malignant melanoma. PET/CT, endoscopy and an esophagogram showed that a 70-mm scaled type 2+1 tumor in the thoracic esophagus and no metastases. We diagnosed a cT3cN0cM0 cStage II tumor. We then performed a subtotal esophagectomy with two-field lymph node dissection and esophagogastrostomy via a retrosternal route. The pathological examination of the resected specimens confirmed that the type 2+1 tumor was PMME (pT2N0M0 pStage II). We administered six courses of postoperative adjuvant chemotherapy with dacarbazine, and the patient has had no recurrence for 17 months after the surgery.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014術前DCF療法が著効した食道原発内分泌細胞癌の１切除例3943ENNaoakiMaedaYasuhiroShirakawaTakeshiKoujimaToshiakiOharaShunsukeTanabeKazuhiroNomaKazuhumiSakuramaToshiyosiFujiwara Esophageal endocrine cell carcinoma is extremely rare. We report a case of esophageal endocrine cell carcinoma showing histological complete response to neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (DCF). A 66-year-old man had been experiencing epigastralgia, and a type 2 tumor in the thoracic part of esophagus was detected by upper endoscopy. The biopsy showed endocrine cell carcinoma. PET/CT, endoscopy and an esophagogram showed that the patient had a 70-mm scaled type 2 tumor in the middle thoracic esophagus, and they also revealed lymph node metastases (no. 106recR). We diagnosed a cT3cN1cM0 cStage III tumor. With two courses of DCF treatment, both the primary tumor and lymph node metastases showed a partial response. We performed a subtotal esophagectomy with three-field lymph node dissection. The pathological examination of the resected specimens revealed no malignant cells in the esophagus or lymph nodes, and we concluded that the pathological effect of the DCF treatment was Grade 3.No potential conflict of interest relevant to this article was reported.Landes BioscienceActa Medica Okayama1538-40471432013Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice230236ENToshioNishikawaMunenoriTakaokaToshiakiOharaYasukoTomonoHuifangHaoXiaohongBaoTakuyaFukazawaZhigangWangKazufumiSakuramaYasuhiroFujiwaraTakayukiMotokiYasuhiroShirakawaTomokiYamatsujiNoriakiTanakaToshiyoshiFujiwaraYoshioNaomotoEsophageal squamous cell carcinoma (ESCC) remains one of the most aggressive cancers with poor prognosis regardless of a several reports that indicate a better therapeutic efficacy using some new chemotherapeutic agents. Recent drug development has contributed to an improved specificity to suppress mTOR activity by which many types of malignancies can be explosively progressed. Temsirolimus (CCI-779, TricelTM) is one of recently synthesized analogs of rapamycin and has provided better outcomes for patients with renal cell carcinoma. In this study, we experimentally evaluated an efficacy of targeting mTOR by temsirolimus for ESCC treatment, with an assessment of its survival advantage using an advanced ESCC animal model.
First, we confirmed that the expression of phosphorylated mTOR was increased in 46 of 58 clinical ESCC tumor tissues (79.3%) and appeared to get strengthened with tumor progression. All of ESCC cell lines used in this study revealed an increase of mTOR phosphorylation, accompanied with the upregulation of hypoxia inducible factor-I alpha (HIF-1 alpha), one of the critical effectors regulated by mTOR. Temsirolimus treatment apparently suppressed the activation of mTOR and its downstream effectors, resulting in the reduced ability of ESCC cell proliferation. Finally, the weekly administration of temsirolimus significantly diminished the size of subcutaneous tumors (vehicle, 3261.6 +/- 722.0; temsirolimus, 599.2 +/- 122.9; p = 0.007) in nude mice and effectively prolonged orthotopic esophageal cancer-bearing mice (median survival periods: control, 31 d; temsirolimus, 43 d; p = 0.0024).
These data suggests that targeting mTOR by temsirolimus may become a therapeutic alternative for esophageal cancer, with a contribution to a better outcome.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0340-700461112012Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells19051916ENRyosukeYoshidaHiroshiTazawaYuuriHashimotoShuyaYanoTeppeiOnishiTsuyoshiSasakiYasuhiroShirakawaHiroyukiKishimotoFutoshiUnoMasahikoNishizakiShunsukeKagawaToshiyoshiFujiwaraTrastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812422012小細胞癌成分を含む食道癌肉腫の１切除例145148ENShunsukeTanabeYasuhiroShirakawaNaoakiMaedaToshiakiOharaKazuhiroNomaKazufumiSakuramaHiroyukiYanaiTomokiYamatsujiYoshioNaomotoToshiyoshiFujiwaraWe experienced a case of esophageal carcinosarcoma with a component of small cell carcinoma. The patient was a 73-year-old man. We administered chemotherapy of CDDP+VP-16, and performed an operation after 2 courses of this chemotherapy. Subtotal esophagectomy and reconstruction with the small intestine was performed. More than three years after resection, he remains alive and recurrence-free. There are few cases of esophageal carcinosarcoma and small cell carcinoma. We report this rare case herein.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812322011テロメラーゼ依存的腫瘍融解アデノウイルス製剤による 放射線感受性増強作用103109ENShinjiKurodaToshiyaFujiwaraYasuhiroShirakawaYasumotoYamasakiSyuyaYanoFutoshiUnoHiroshiTazawaYuuriHashimotoYuichiWatanabeKazuhiroNomaYasuoUrataShunsukeKagawaToshiyoshiFujiwaraDNA修復機能阻害は放射線感受性を増強させるため，DNA修復に関与する因子の阻害剤は放射線増感剤となり得る．我々の開発したテロメラーゼ依存的腫瘍融解アデノウイルス製剤OBP-301（テロメライシン）は，アデノウイルスE1B55kDaタンパクを介して細胞のDNA修復に重要な役割を果たすMRN複合体（Mre11，Rad50，NBS1）を分解する機能を有する．このMRN複合体の分解によりATM（ataxia-telangiectasia mutated）の活性化が抑制され結果的にDNA修復機構が阻害される．我々はOBP-301と放射線との併用が強力な相乗効果を生み出すことをマウスの皮下腫瘍モデルおよび食道癌同所性モデルにおいて証明した．これらの結果はOBP-301が将来有望な放射線増感剤となり得ることだけでなく，E1B55kDaタンパクを産生する腫瘍融解アデノウイルス製剤と放射線との併用が悪性腫瘍に対する有力な治療戦略となり得ることを示す．No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812212010Focal adhesion kinase (FAK) と Insulin-like growth factor-I receptor (IGF-IR) に対するデュアルチロシンキナーゼ阻害剤の食道腺癌における抗腫瘍効果1725ENNobuyukiWatanabeMunenoriTakaokaKazufumiSakuramaYasukoTomonoShinjiHatakeyamaOsamuOhmoriTakayukiMotokiYasuhiroShirakawaTomokiYamatsujiMinoruHaisaJunjiMatsuokaDavid G.BeerHitoshiNagatsukaNoriakiTanakaYoshioNaomotoNo potential conflict of interest relevant to this article was reported.岡山大学医学部保健学科Acta Medica Okayama1345-09481512004インピーダンス咽頭図(IPG)を用いた加齢による嚥下機能減退の定量的評価法17ENToshimasaKusuharaTakaoNakamuraKeikoMoriYoshitakeYamamotoYasuhiroShirakawaYoshioNaomoto10.18926/15189インピーダンス咽頭図(Impedance Pharyngography, 以下IPG)は嚥下活動中の頸部電気インピーダンスを測定するもので,嚥下機能評価を簡便かつ無侵襲に行うことができる手法である｡IPG波形は嚥下機能を反映するものであるが嚥下機能の減退による波形への影響はその原因により様々である｡すなわち嚥下機能の状態が異なる被験者のIPG波形を直接比較･診断することは測定者の主観に依存することになり客観性に欠ける｡本研究では,まず青年健常者のNormal IPGをもとに嚥下機能が反映される波形の特徴を評価するパラメータとして,咽頭通過時間,インピーダンス変化率,類似度,嚥下音タイミングの4つを採用し,IPCを定量的に評価する手法を提案した｡また,この評価法を高齢者のIPGに適用し,青年健常者に比べて嚥下活動に関与する器官が円滑に活動を履行する能力に減退が生じる様子を定量的に示した｡No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812112009中国四国広域プロ養成プログラム ―チーム医療を担うがん専門医療人の育成―www.chushiganpro.jp2933ENJunjiMatsuokaYoshioNaomotoMasahiroTabataYasuhiroShirakawaKatsuyukiHottaMitsuneTanimotoNoriakiTanakaNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811632005ヒトの大腸癌細胞におけるTNFとINF-αの併用刺激によるApoptosisの増強のメカニズム, 特にNF-κBが誘導するFasの発現の増強を介した新しいシグナル伝達について―岡山大学医学賞（林原賞）を受賞して―221228ENNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811812006早期診断し得た食道癌術後静脈血栓塞栓症の2例4145ENTakashiKanazawaNobuyukiWatababeYoshioNaomotoMasahikoKobayashiYasuhiroShirakawaTomokiYamatsujiNaoyaKobayashiTohsiyoshiFujiwaraNagahideMatsubaraHiromiIwagakiJunjiMatsuokaNoriakiTanakaWe encountered two cases of pulmonary embolism (PE)/venous thrombs (DVT) after surgery for esophageal cancer. The first case was a 58-year-old male. He underwent a subtotal esophagectomy and reconstruction using the stomach via the subcutaneus route. His postoperative course was stable; however, 13 days after the operation､ he had an elevated fever and pulmonary thrombi were observed on CT-scan screening. Scintigraphy confirmed the thrombi. An inferior vena cava filter (IVCF) was inserted and anti-coagulation therapy using heparin was started. His fever subsided, and 35 days after the operation, the thrombi disappeared. He was discharged thereafter and is being followed up using warfarin. The second case was a 74-year-old male. He also underwent subtotal esophagectomy and reconstruction using the stomach via the subcutaneus route. A central line was inserted via right femoral vein; however, the artery was injured and pressurization to the vessel was needed. His post-operative course was stable and symptom-free; however, ultrasound screening detected DVT in his right femoral vein. IVCF was mserted and anti-coagulation therapy was begun, thrombi disappeared 8 days after the therapy.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811822006気管冷却下に施行した縦隔リンパ節転移に対するラジオ波焼灼療法105108ENNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811922007食道扁平上皮癌の発癌過程におけるDNAメチル化の役割113117ENTatsuhiroIshiiJunMurakamiKenjiNotoharaHiromiSasamotoTakeshiKambaraYasuhiroShirakawaYoshioNaomotoMamoruOuchidaKenjiShimizuR. JassJeremyNagahideMatsubaraNoriakiTanakaNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155812012008X 消化管がんに対する現代の標準的治療 〜外科的治療を中心に〜5561ENYoshioNaomotoTomokiYamatsujiYasuhiroShirakawaMunenoriTakaokaYasuhiroFujiwaraShunsukeTanabeNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2001Topological Analysis of p21WAF1/CIP1 Expression in Esophageal Squamous DysplasiaENNo potential conflict of interest relevant to this article was reported.