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講演・口頭発表等 - 大脇　哲洋

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松本正隆, 夏越祥次, 奥村浩, 内門泰斗, 瀬戸山徹郎, 佐々木健, 櫻井俊秀, 尾本至, 花園幸一, 大脇哲洋, 石神純也, 帆北修一, 野村秀洋, 愛甲孝 . HP-017-8 同時性食道胃重複癌の進行度別治療法の検討(食道(手術3),ハイブリッドポスター,第109回日本外科学会定期学術集会) . 日本外科学会雑誌 2009年2月一般社団法人日本外科学会

Matsumoto M., Kashima S., Owaki T., Iguchi S., Inoue K., Tazuma S., Maeda T. . Geographic Distribution of Regional Quota Program Graduates of Japanese Medical Schools: A Nationwide Cohort Study . Academic Medicine 2019年 Academic Medicine

記述言語：日本語

Purpose To show the practice location of graduates from two Japanese programs recruiting physicians to rural areas: a regional quota program of medical schools and a prefecture scholarship program (a prefecture is an administrative geographic division). Graduates of each program must work in a designated rural prefecture for a fixed period. Method A nationwide cohort study was conducted for three groups of participants graduating between 2014 and 2016: quota graduates without scholarship (quota alone), nonquota graduates with scholarship (scholarship alone), and quota graduates with scholarship. A questionnaire was sent via medical school or prefecture office to each potential subject to collect baseline individual data, including home prefecture and graduation year. Data were connected through physician identification number to the Physician Census 2016 of the Ministry of Health, Labour and Welfare to identify the subjects' practice location and compared with data for other physicians in the census. Comparisons were conducted with Mann-Whitney and chi-square tests. Results The proportion of physicians working in nonmetropolitan municipalities for quota alone (185/244; 75.8%), scholarship alone (305/363; 84.0%), and quota with scholarship (341/384; 88.8%) was significantly higher than for other physicians (13,299/22,906; 58.1%). Median population density of the municipalities where subjects worked for quota alone (1,042.4 persons per square kilometer), scholarship alone (613.5), and quota with scholarship (547.4) was significantly lower than that for other physicians (3,214.0). These disparities increased with number of years since graduation. Conclusions The regional quota and prefecture scholarship programs succeeded in producing physicians who practiced in rural areas of Japan.

DOI： 10.1097/ACM.0000000000002688

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Matsumoto M., Takeuchi K., Tanaka J., Tazuma S., Inoue K., Owaki T., Iguchi S., Maeda T. . Follow-up study of the regional quota system of Japanese medical schools and prefecture scholarship programmes: A study protocol . BMJ Open 2016年 BMJ Open

記述言語：日本語

Introduction: Given the shortage of physicians, particularly in rural areas, the Japanese government has rapidly expanded the number of medical school students by adding chiikiwaku (regional quotas) since 2008. Quota entrants now account for 17% of all medical school entrants. Quota entrants are usually local high school graduates who receive a scholarship from the prefecture government. In exchange, they temporarily practise in that prefecture, including its rural areas, after graduation. Many prefectures also have scholarship programmes for non-quota students in exchange for postgraduate in-prefecture practice. The objective of this cohort study, conducted by the Japanese Council for Community-based Medical Education, is to evaluate the outcomes of the quota admission system and prefecture scholarship programmes nationwide. Methods and analysis: There are 3 groups of study participants: quota without scholarship, quota with scholarship and non-quota with scholarship. Under the support of government ministries and the Association of Japan Medical Colleges, and participation of all prefectures and medical schools, passing rate of the National Physician License Examination, scholarship buy-out rate, geographic distribution and specialties distribution of each group are analysed. Participants who voluntarily participated are followed by linking their baseline information to data in the government's biennial Physician Census. Results to date have shown that, despite medical schools' concerns about academic quality, the passing rate of the National Physician License Examination in each group was higher than that of all medical school graduates. Ethics and dissemination: The Ethics Committee for Epidemiological Research of Hiroshima University and the Research Ethics Committee of Nagasaki University Graduate School of Biomedical Sciences permitted this study. No individually identifiable results will be presented in conferences or published in journals. The aggregated results will be reported to concerned government ministries, associations, prefectures and medical schools as data for future policy planning.

DOI： 10.1136/bmjopen-2016-011165

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Okumura H, Uchikado Y, Omoto I, Motomura M, Kita Y, Sasaki K, Noda M, Arigami T, Uenosono Y, Baba K, Mori S, Kijima Y, Nakajo A, Kurahara H, Maemura K, Sakoda M, Owaki T, Ishigami S, Natsugoe S . Ferredoxin Reductase Is Useful for Predicting the Effect of Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma. . Anticancer research 2015年12月

Okumura H., Uchikado Y., Omoto I., Motomura M., Kita Y., Sasaki K., Noda M., Arigami T., Uenosono Y., Baba K., Mori S., Kijima Y., Nakajo A., Kurahara H., Maemura K., Sakoda M., Owaki T., Ishigami S., Natsugoe S. . Ferredoxin reductase is useful for predicting the effect of chemoradiation therapy on esophageal squamous cell carcinoma . Anticancer Research 2015年12月 Anticancer Research

記述言語：日本語

Background: Ferredoxin reductase (Fdxr) is the mitochondrial cytochrome P-450 NADPH reductase. Fdxr overexpression increases the sensitivity of tumor cells to apoptosis in response to chemotherapy through reactive oxygen species (ROS) production. The aim of the present study was to examine the Fdxr expression in esophageal squamous cell carcinoma (ESCC) and determine if the expression is useful for predicting response to chemoradiation therapy (CRT). Materials and Methods: Fdxr expression in biopsy specimens from 50 patients before neoadjuvant CRT were immunohistochemically examined. Then, the correlation between Fdxr expression and response to CRT were analyzed. Results: Both clinically and histologically, significant correlations were found between positive Fdxr expression and favorable response to CRT. Furthermore, Fdxr was significantly correlated with postoperative outcomes and was found to be an independent prognostic factor. Conclusion: Fdxr expression was found to be closely related to the effect of CRT and could predict the CRT outcome in patients with ESCC.

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Omoto I., Matsumoto M., Okumura H., Uchikado Y., Setoyama T., Kita Y., Owaki T., Kijima Y., Shinchi H., Ishigami S., Ueno S., Natsugoe S. . Expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 in esophageal squamous cell carcinoma . Oncology Letters 2014年4月 Oncology Letters

記述言語：日本語

Lymph node metastasis is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor (VEGF)-C and its receptor, VEGF receptor-3 (VEGFR-3), are key in the process of lymphangiogenesis. The present study immunohistochemically examined the expression of VEGF-C, VEGFR-3 and D2-40 in 119 patients with ESCC, and microlymphatic vessel density (MLVD) was calculated based on D2-40 expression counts. Positive expression of VEGF-C was found to correlate significantly with depth of tumor invasion, lymphatic invasion and lymph node metastasis (P<0.001, P<0.0001 and P<0.0001, respectively). Patients with deeper tumor invasion showed higher positivity of VEGFR-3 expression (P<0.05), while patients with lymph node metastasis showed higher MLVD (P<0.05). When patients were divided into three groups according to the expression of VEGF-C and VEGFR-3, patients with coexpression of VEGF-C and VEGFR-3 exhibited poorer prognosis and higher MLVD. The VEGF-C/VEGFR-3 axis is important in tumor lymphangiogenesis.

DOI： 10.3892/ol.2014.1823

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Higo N., Okumura H., Uchikado Y., Omoto I., Sasaki K., Kita Y., Ryosuke D., Noda M., Owaki T., Ishigami S., Natsugoe S. . Expression of SOX9 is related to prognosis in patients with oesophageal squamous cell carcinoma . In Vivo 2018年7月 In Vivo

記述言語：日本語

Background: Sex-determining region Y-box 9 (SOX9) is an important transcription factor for the development and differentiation of cells and their organization. In the present study, the clinical significance of SOX9 expression in oesophageal squamous cell carcinoma was examined. Materials and Methods: SOX9 expression in surgical specimens of primary tumours were immunohistochemically investigated in 175 patients with oesophageal squamous cell carcinomas. Results: SOX9 was expressed (moderately or strongly) in 62.9% of samples. Expression of SOX9 was significantly positively correlated with depth of invasion, advanced stage, lymphatic and venous invasion, and poor prognosis. Univariate analysis showed that depth of invasion, lymph node metastasis, distant metastasis, stage, lymphatic invasion, venous invasion, and SOX9 expression were prognostic factors. Multivariate analysis indicated that depth of invasion and stage were independent prognostic factors, but SOX9 expression was not. Conclusion: SOX9 expression is related to prognosis in patients with oesophageal squamous cell carcinoma, although it is not an independent prognostic factor.

DOI： 10.21873/invivo.11316

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Okumura H., Natsugoe S., Yokomakura N., Kita Y., Matsumoto M., Uchikado Y., Setoyama T., Owaki T., Ishigami S., Aikou T. . Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma . Clinical Cancer Research 2006年6月 Clinical Cancer Research

記述言語：日本語

Purpose: The p53 gene and its family are important factors for carcinogenesis, prognosis, and chemoresistance in esophageal squamous cell carcinoma. A recently identified ribonucleotide reductase, p53R2, is regulated by p53 for supplying nucleotides to repair damaged DNA. In the present study, we analyzed the expression and clinicopathologic significance of p53 and p53R2 in esophageal squamous cell carcinoma. Experimental Design: We immunohistochemically investigated the relationship between p53 and p53R2 expressions in surgical specimens of primary tumors in 222 patients with esophageal squamous cell carcinoma. Results: The positive expression rate of p53 was 47.1% and that of p53R2 was 61.7%. Positive p53R2 expression was significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis. In the p53-negative group, the 5-year survival rate was better in patients with negative p53R2 expression than in those with positive p53R2 expression. Multivariate analysis indicated that the negative expression of both p53 and p53R2 was an independent prognostic factor along with tumor depth nodal metastasis and stage. Conclusions: We showed that positive p53R2 expression was related to tumor development and that alteration of p53R2 expression in p53-negative tumors was closely related to prognosis. Evaluation of the expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma. © 2006 American Association for Cancer Research.

DOI： 10.1158/1078-0432.CCR-05-2416

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Kita Y., Natsugoe S., Okumura H., Matsumoto M., Uchikado Y., Setoyama T., Owaki T., Ishigami S., Aikou T. . Expression of Osteopontin in oesophageal squamous cell carcinoma . British Journal of Cancer 2006年9月 British Journal of Cancer

記述言語：日本語

Osteopontin is a multifunctional 34 kDa extracellular matrix protein with a cell-binding domain. It is involved cell adhesion and cell migration and is therefore considered to influence tumorigenesis and/or metastasis. The purpose of the present study was to evaluate the clinical significance of Osteopontin expression in oesophageal squamous cell carcinoma (ESCC). In the present study, we immunohistochemically investigated the relationship between Osteopontin expression and clinicopathological factors including prognosis in surgical specimens of primary tumours in 175 patients with ESCC. Osteopontin was expressed in 48% of 175 patients. Osteopontin expression was significantly correlated with lymph node metastasis, lymphatic invasion, and stage (P=0.0015, 0.037 and 0.033, respectively). Tumours with expressing Osteopontin exhibited more lymph node metastasis, lymphatic invasion and advanced stage than the tumour with negative Osteopontin expression. Five-year survival rate was better in patients with negative Osteopontin expression than in those with positive Osteopontin expression (P=0.035). However, multivariate analysis revealed that Osteopontin expression was not an independent prognostic factor. As our findings suggest that Osteopontin may play an important role in progress of ESCC, the evaluation of Osteopontin expression is useful for predicting the malignant properties of ESCC. © 2006 Cancer Research.

DOI： 10.1038/sj.bjc.6603296

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Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, Uchikado Y, Kita Y, Tamotsu K, Hanazono K, Owaki T, Aikou T . Expression of CXCL12 and its receptor CXCR4 in esophageal squamous cell carcinoma. . Oncology reports 2009年1月

Sasaki K., Natsugoe S., Ishigami S., Matsumoto M., Okumura H., Setoyama T., Uchikado Y., Kita Y., Tamotsu K., Sakurai T., Owaki T., Aikou T. . Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancer . Journal of Surgical Oncology 2008年4月 Journal of Surgical Oncology

記述言語：日本語

Background and Objectives: The chemokine CXCL12 and its receptor CXCR4 are involved in cell migration, proliferation, and angiogenesis, and promote organ-specific localization of distant metastases in various carcinomas. We examined their expression and microvessel density (MVD) in submucosal esophageal squamous cell carcinoma (ESCC) and analyzed their connection to clinicopathological findings including lymph node micrometastasis (LMM). Methods: Eighty-six patients with submucosal ESCC underwent curative resection from 1985 to 2002. Immunohistochemical staining of CXCL12, CXCR4, and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. MVD was calculated from CD34 expression, and LMM detected by cytokeratin staining. Results: Expression of CXCL12, but not CXCR4, correlated with lymph node metastasis. There was no significant correlation between the expression of CXCL12 and/or CXCR4 and MVD. LMM was detected in 8 cases and 14 lymph nodes. CXCL12 expression and high MVD were found in tumors with lymph node metastasis including LMM. Furthermore, in the CXCR4-positive tumors, positive CXCL12 expression was more significantly correlated with lymph node metastasis and/or LMM than negative CXCL12 expression. Conclusions: Evaluation of CXCL12 and CXCR4 expression should assist detection of lymph node metastasis including LMM in submucosal ESCC. © 2008 Wiley-Liss, Inc.

DOI： 10.1002/jso.20976

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Matsumoto M., Uchikado Y., Kita Y., Omoto I., Setoyama T., Okumura H., Owaki T., Ishigami S., Ueno S., Natsugoe S. . Esophageal squamous cell carcinoma co-existing with achalasia: Report of two cases . Esophagus 2011年6月 Esophagus

記述言語：日本語

Esophageal achalasia is a primary motility disorder of the esophagus. Although various treatments can relieve the symptoms, esophageal cancer arising in patients with achalasia is the most important problem for long-term survivors. We encountered 2 cases of esophageal squamous cell carcinoma co-existing with achalasia that had been diagnosed 27 and 30 years earlier, respectively. Neither patient had been aware of dysphagia due to dilatation of the esophagus. Both patients underwent esophagectomy via right thoracotomy. Although esophagectomy with radical lymphadenectomy was performed successfully in one case of submucosal cancer, the primary tumor in the other case was more invasive and aggressive than indicated by the preoperative clinical diagnosis, and could not be completely resected. Regular endoscopic examination should be scheduled for long-term survivors of achalasia in order to detect esophageal cancer early and evaluate any changes in the esophagus carefully. © The Japan Esophageal Society and Springer 2011.

DOI： 10.1007/s10388-011-0272-x

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Sasaki K., Natsugoe S., Higashi M., Okumura H., Matsumoto M., Hanazono K., Setoyama T., Yanagi M., Owaki T., Ishigami S., Yonezawa S., Aikou T. . Esophageal carcinosarcoma with granulocyte colony-stimulating factor: A case report . Esophagus 2007年9月 Esophagus

記述言語：日本語

A 62-year-old man was admitted to our hospital for dysphagia, leukocytosis, and pyrexia. The serum level of granulocyte colony-stimulating factor (G-CSF) was high and immunostaining of a biopsy specimen of esophageal tumor using anti-granulocyte-macrophage colony-stimulating factor (anti-GM-CSF) antibody demonstrated GM-CSF expression in the cytoplasm of the tumor cells. After esophagectomy, the leukocyte count and serum G-CSF level normalized. Histologically, this tumor was diagnosed as a carcinosarcoma with two components: squamous cell carcinoma and sarcoma. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, tumor cells were positive for Ki-67, cyclin D1, p53, and epidermal growth factor receptor (EGFR), which were related to the acquisition of more aggressive tumor behavior. Although G-CSF-producing esophageal carcinosarcoma is very rare, we should consider such disease when a patient has symptoms of leukemia such as leukocytosis and high fever. © 2007 Japan Esophageal Society and Springer-Verlag.

DOI： 10.1007/s10388-007-0121-0

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Sakamoto F, Natsugoe S, Yoshinaka H, Shimada M, Owaki T, Nakano S, Baba M, Aikou T . Endosonographic detection of mediastinal lymph node metastasis in superficial carcinoma of the esophagus: assessment by type classification and histogram. . Journal of gastroenterology 2004年1月

SAKAMOTO FUMINORI, NATSUGOE SHOJI, YOSHINAKA HEIJI, SHIMADA MARIO, OWAKI TETSUHIRO, NAKANO SHIZUO, BABA MASAMICHI, AIKOU TAKASHI . Endosonographic detection of mediastinal lymph node metastasis in superficial carcinoma of the esophagus : assessment by type classification and histogram . 2004年1月

Owaki T., Matsumoto M., Okumura H., Uchicado Y., Kita Y., Setoyama T., Sasaki K., Sakurai T., Omoto I., Shimada M., Sakamoto F., Yoshinaka H., Ishigami S., Ueno S., Natsugoe S. . Endoscopic ultrasonography is useful for monitoring the tumor response of neoadjuvant chemoradiation therapy in esophageal squamous cell carcinoma . American Journal of Surgery 2012年2月 American Journal of Surgery

記述言語：日本語

Background: Recently, neoadjuvant chemoradiation therapy (CRT) has been introduced for treatment of esophageal squamous cell carcinoma (ESCC). This study was performed to investigate the usefulness of endoscopic ultrasonography (EUS) in comparison with EUS findings before and after CRT, and histologic findings. Methods: There were 33 patients with potentially resectable ESCC who underwent neoadjuvant CRT. Preoperative EUS and histologic findings were compared. EUS criteria were established on the basis of low and high echoic regions. Resected specimens were examined by hematoxylin-eosin, azan, and cytokeratin immunohistochemical staining. Results: Azan and cytokeratin staining clearly delineated fibrous changes and residual tumor. Low echoic regions corresponded to residual tumor and high echoic spots corresponded to fibrosis. All 12 patients classified as grade 1 on EUS diagnosis had histologic grade 1 tumors. Nineteen of 21 cases that presented with high echo were grade 2 or 3. The prognosis according to EUS diagnosis was similar to the histologic effect. Conclusions: Preoperative EUS findings reflected the histologic effect after neoadjuvant CRT. EUS is a useful tool to assess the effect for CRT and to predict the prognosis in ESCC patients. © 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjsurg.2011.01.027

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Sakurai T, Okumura H, Matsumoto M, Uchikado Y, Owaki T, Kita Y, Setoyama T, Omoto I, Kijima Y, Ishigami S, Natsugoe S . Endoglin (CD105) is a useful marker for evaluating microvessel density and predicting prognosis in esophageal squamous cell carcinoma. . Anticancer research 2014年7月

Sakurai T., Okumura H., Matsumoto M., Uchikado Y., Owaki T., Kita Y., Setoyama T., Omoto I., Kijima Y., Ishigami S., Natsugoe S. . Endoglin (CD105) is a useful marker for evaluating microvessel density and predicting prognosis in esophageal squamous cell carcinoma . Anticancer Research 2014年7月 Anticancer Research

記述言語：日本語

Background: Angiogenic molecular markers such as vascular endothelial growth factor and tumor microvessel density reflect prognosis of human cancers. The present study clarified the usefulness of endothelial marker endoglin (CD 105) by assessing microvessel density in esophageal squamous cell carcinoma (ESCC). Materials and Methods: We immunohistochemically investigated CD105, CD31, and vascular endothelial growth factor-A VEGF-A expression in primary esophageal squamous cell carcinoma specimens from 142 patients. Results: Microvessel density was 35.9±21.2 for CD105 and 46.3±25.4 for CD31. CD105 microvessel density was significantly associated with tumor length, tumor invasion depth, lymph node metastasis, stage, lymphatic invasion, venous invasion, and VEGF-A expression; its correlation with almost all clinicopathological parameters was stronger than CD31 microvessel density. And significantly better prognosis was achieved in patients with low, compared to high CD105, microvessel density. Conclusion: CD105 microvessel density reflected the degree of angiogenesis and prognosis in patients with esophageal squamous cell carcinoma.

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中野静雄, 夏越祥次, 衣裴勝彦, 上之園芳一, 馬場道宏, 池田直徳, 松本正隆, 奥村浩, 大脇哲洋, 愛甲孝 . EMR治療後の長期予後からみた,食道表在癌治療法の検討 . 日本消化器外科学会雑誌 2003年7月一般社団法人日本消化器外科学会

Yoshida S., Matsumoto M., Kashima S., Owaki T., Iguchi S., Inoue K., Tazuma S., Maeda T. . Emigration of regional quota graduates of Japanese medical schools to non-designated prefectures: A prospective nationwide cohort study . BMJ Open 2019年7月 BMJ Open

記述言語：日本語

Objectives: This study examined the retention of regional quota graduates of Japanese medical schools and prefecture scholarship recipients within their designated prefectures where they are obliged or expected to work and revealed the personal and regional characteristics associated with their emigration to non-designated prefectures. Regional quota and prefecture scholarship are two of the most ambitious policies ever conducted in Japan for recruiting physicians to practice in rural areas. Design: Prospective cohort study. Setting: Nationwide. Participants: Regional quota graduates with prefecture scholarship, quota graduates without scholarship and non-quota graduates with scholarship of Japanese medical schools who obtained their physician license between 2014 and 2016. Primary outcome: The emigration in 2016 of the participants from the designated prefectures. Results: Total participants were 991 physicians, three of whom were excluded due to the missing values of crucial items, leaving 988 participants for analysis (quota with scholarship 387, quota alone 358 and scholarship alone 243). The percentage of those who emigrated was 11.9% (118/988). The mean (±SD) proportion of subjects who emigrated was 11.7% (±10.3) among all prefectures and the proportion varies widely among prefectures (0%-44.4%). Multilevel logistic regression analysis showed those who received prefecture scholarship (OR 0.23; 95% CI 0.08 to 0.67) and whose designated prefecture has an ordinance-designated city (ie, large city) were less likely to emigrate (OR 0.47; 95% CI 0.24 to 0.90). In contrast, graduates from a medical school outside the designated prefecture (OR 4.20; 95% CI 2.20 to 7.67) and who have a right to postpone their obligatory service (OR 3.42; 95% CI 1.52 to 7.67) were more likely to emigrate. Conclusions: A substantial proportion of regional quota graduates and prefecture scholarship recipients emigrated to non-designated prefectures. Emigrations should be reduced by improving the potential facilitators for emigration such as discordance in location between medical school and designated prefecture.

DOI： 10.1136/bmjopen-2019-029335

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