Updated on 2023/04/18

写真a

 
KURIMOTO Keisuke
 
Organization
Nagoya University Hospital Assistant professor of hospital
Title
Assistant professor of hospital

Degree 1

  1. PhD ( 2019.3   Nagoya University ) 

Research Interests 4

  1. clinical oncology

  2. hepatobiliary and pancreatic surgery

  3. gastroenterological surgery

  4. molecular biology

Research Areas 2

  1. Life Science / Tumor biology  / clinical oncology

  2. Life Science / Digestive surgery  / hepatobiliary and pancreatic surgery

Research History 3

  1. Nagoya University   Graduate School of Medicine   Assistant Professor

    2019.4

  2. Ministry of Health, Labour and Welfare

    2018.4 - 2019.3

  3. Ministry of Health, Labour and Welfare

    2016.7 - 2018.3

 

Papers 27

  1. 増刊号 術前画像の読み解きガイド-的確な術式選択と解剖把握のために Ⅶ 後腹膜 後腹膜腫瘍

    横山 幸浩, 砂川 真輝, 栗本 景介, 江畑 智希, 小寺 泰弘

    臨床外科   Vol. 77 ( 11 ) page: 325 - 329   2022.10

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    Publisher:株式会社医学書院  

    DOI: 10.11477/mf.1407213928

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  2. ASO Visual Abstract: Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9. International journal

    Masaya Yamanaka, Masamichi Hayashi, Fuminori Sonohara, Suguru Yamada, Haruyoshi Tanaka, Akihiro Sakai, Shinji Mii, Daigo Kobayashi, Keisuke Kurimoto, Nobutake Tanaka, Yoshikuni Inokawa, Hideki Takami, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Annals of surgical oncology   Vol. 29 ( 11 ) page: 7192 - 7193   2022.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1245/s10434-022-12084-0

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  3. Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9. International journal

    Masaya Yamanaka, Masamichi Hayashi, Fuminori Sonohara, Suguru Yamada, Haruyoshi Tanaka, Akihiro Sakai, Shinji Mii, Daigo Kobayashi, Keisuke Kurimoto, Nobutake Tanaka, Yoshikuni Inokawa, Hideki Takami, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Annals of surgical oncology   Vol. 29 ( 11 ) page: 7180 - 7189   2022.10

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    BACKGROUND: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers. METHODS: We found through analysis of the public database that ROBO4, one of the axon guidance molecules among the SLIT/ROBO family, is significantly downregulated in primary pancreatic cancer tissues compared with adjacent normal tissues. We carried out transfection experiments using three pancreatic cancer cell lines (MiaPaCa-2, BxPC-3, and SW1990) and one pancreatic duct epithelial cell line (HPDE6c7). A total of 51 clinical samples were then examined by immunohistochemical staining to find an association between ROBO4 expression at the protein level, clinical characteristics, and surgical outcomes. RESULTS: ROBO4 overexpression suppressed the invasion and migration abilities in MiaPaCa-2 and BxPC-3, while ROBO4 siRNA transfection to SW1990 and HPDE6c7 enhanced those activities. PCR-based profiling detected MMP-9 as a candidate downstream target of ROBO4, which was validated by decreased MMP-9 activity after the ROBO4 overexpression assay. High ROBO4 expression clinical samples had significantly better overall survival rather than low ROBO4 cases (P = 0.048). CONCLUSION: These findings suggest that decreased ROBO4 expression activates malignant phenotypes in cancer cells and is correlated with poor survival outcomes in pancreatic cancer.

    DOI: 10.1245/s10434-022-12039-5

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  4. FOCUS 後腹膜肉腫診療ガイドラインの要点と今後の展望

    横山 幸浩, 砂川 真輝, 栗本 景介, 江畑 智希, 小寺 泰弘

    臨床外科   Vol. 77 ( 9 ) page: 1108 - 1112   2022.9

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    Publisher:株式会社医学書院  

    DOI: 10.11477/mf.1407213835

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  5. Comparison Between FOLFIRINOX and nal-IRI/FL as Second-line Treatment After Gemcitabine Plus Nab-paclitaxel for Pancreatic Cancer br

    Otsu Tomohisa, Inokawa Yoshikuni, Takami Hideki, Hayashi Masamichi, Kurimoto Keisuke, Tanaka Nobutake, Tanaka Haruyoshi, Shimizu Dai, Hattori Norifumi, Kanda Mitsuro, Tanaka Chie, Nakayama Goro, Kodera Yasuhiro

    ANTICANCER RESEARCH   Vol. 42 ( 8 ) page: 3889 - 3894   2022.8

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    Background/Aim: The regimen of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin (Nal-IRI/FL) was approved in Japan as second-line chemotherapy after gemcitabine-based treatment for pancreatic ductal adenocarcinoma (PDAC) in 2020. We examined the difference in outcome between patients treated with second-line folinic acid, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and those treated with nal-IRI/FL after first-line gemcitabine and nab-paclitaxel (GnP). Patients and Methods: The outcomes of 34 patients with PDAC who received second-line FOLFIRINOX (n=21) or nal-IRI/FL (n=13) after GnP at our Department from January 2016 to June 2021 were reviewed retrospectively. Results: Patient backgrounds did not differ between the groups. Dose reduction was more frequently required for treatment with FOLFIRINOX than with nal-IRI/FL (86% vs. 46%, p=0.022). Pegfilgrastim and aprepitant were used more frequently in the FOLFIRINOX group (both p<0.01). Progression-free survival (5.9 vs. 8.3 months) and overall survival (9.1 vs. 11.2 months) did not differ significantly between the groups. The frequency of grade 3 (Common Terminology Criteria for Adverse Events) or higher adverse events was similar between the groups. All-grade peripheral neuropathy was more common in the FOLFIRINOX group (100% vs. 77%, p=0.048). Conclusion: FOLFIRINOX and nal-IRI/FL as second-line therapy after GnP provided similar prognoses, although supportive treatment and dose reduction were more frequently required for FOLFIRINOX.

    DOI: 10.21873/anticanres.15882

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  6. Synopsis of a clinical practice guideline for pancreatic ductal adenocarcinoma with peritoneal dissemination in Japan; Japan Peritoneal Malignancy Study Group

    Satoi Sohei, Takahara Naminatsu, Fujii Tsutomu, Isayama Hiroyuki, Yamada Suguru, Tsuji Yasushi, Miyato Hideyo, Yamaguchi Hironori, Yamamoto Tomohisa, Hashimoto Daisuke, Yamaki So, Nakai Yousuke, Saito Kei, Baba Hayato, Watanabe Toru, Ishii Shigeto, Hayashi Masamichi, Kurimoto Keisuke, Shimada Hideaki, Kitayama Joji

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES   Vol. 29 ( 6 ) page: 600 - 608   2022.6

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    Language:English   Publisher:Journal of Hepato-Biliary-Pancreatic Sciences  

    Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels (“strong”, “medium”, “weak”, “very weak”). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. These guidelines address three subjects: diagnostic, chemotherapeutic, and surgical approaches. They include nine clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one “column”. This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

    DOI: 10.1002/jhbp.1085

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  7. Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy. International journal

    Yuki Sunagawa, Masamichi Hayashi, Suguru Yamada, Hiroshi Tanabe, Keisuke Kurimoto, Nobutake Tanaka, Fuminori Sonohara, Yoshikuni Inokawa, Hideki Takami, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Clinical epigenetics   Vol. 13 ( 1 ) page: 172 - 172   2021.12

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    BACKGROUND: Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. METHODS: We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017-2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. RESULTS: Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352-9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). CONCLUSION: Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

    DOI: 10.1186/s13148-021-01165-8

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  8. 右側肝円索に合併した胆嚢癌の1例

    鈴木 雄之典, 猪川 祥邦, 栗本 景介, 田中 伸孟, 園原 史訓, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: P126 - 6   2021.7

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  9. 膵癌に対する術前AGRと臨床病理学的因子や予後に関する検討

    小林 大悟, 林 真路, 加藤 吉康, 栗本 景介, 田中 伸孟, 砂川 祐輝, 園原 史訓, 猪川 祥邦, 高見 秀樹, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: P129 - 4   2021.7

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  10. miR-23b-3p Plays an Oncogenic Role in Hepatocellular Carcinoma. International journal

    Masamichi Hayashi, Suguru Yamada, Keisuke Kurimoto, Hiroshi Tanabe, Sho Hirabayashi, Fuminori Sonohara, Yoshikuni Inokawa, Hideki Takami, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Annals of surgical oncology   Vol. 28 ( 6 ) page: 3416 - 3426   2021.6

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    BACKGROUND: Reports show miR-23b to be a cancer-related biomarker in various cancer types. Interestingly, it has a dual role of oncogenic and tumor-suppressive functions, depending on the cancer type. This study focused on the unknown association of miR-23b-3p with hepatocellular carcinoma (HCC). METHODS: Expression of miR-23b-3p was measured in nine HCC cell lines and 125 resected human HCC samples by TaqMan microRNA assays. To detect its downstream target, miR-23b-3p mimic and inhibitor constructs were transfected and analyzed. RESULTS: HepG2, a high miR-23b-3p-expressing cell line, was transfected with a miR-23b-3p inhibitor construct, whereas SK-Hep1, a low miR-23b-3p-expressing cell line, was transfected with a mimic construct. Proliferation of HCC cells was activated by miR-23b-3p overexpression and diminished by its knockdown. Then, 125 clinical HCC samples were examined to measure miR-23b-3p expression. Tumor expression of miR-23b-3p was upregulated in 48 cases (38%) and downregulated in 77 cases (62%). The upregulated cases were correlated with elderly patients (P = 0.015). These patients also showed significantly poor overall survival [hazard ratio (HR), 3.10; 95% conflidence interval (CI), 1.57-6.29; P = 0.001] in a multivariate analysis. Furthermore, mitochondrial metabolism-related genes (MICU3 and AUH) were detected as specific binding targets. CONCLUSION: The study showed that miR-23b-3p functions as an oncogenic microRNA in HCC cell lines. Its overexpression in resected HCC tissues was a significant prognostic factor of overall survival. Both MICU3 and AUH may be candidate gene targets of miR-23b-3p.

    DOI: 10.1245/s10434-020-09283-y

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  11. パンデミック下における外科卒前教育の工夫

    高見 秀樹, 小池 聖彦, 鈴木 雄之典, 栗本 景介, 田中 伸孟, 柴田 雅央, 園原 史訓, 武内 大, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 田中 知恵, 山田 豪, 中山 吾郎, 菊森 豊根, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SP - 7   2021.4

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  12. 転移性肝腫瘍に対する至適治療戦略 術前化学療法の可否につき考える

    林 真路, 山田 豪, 高見 秀樹, 猪川 祥邦, 園原 史訓, 田中 伸孟, 栗本 景介, 砂川 祐輝, 加藤 吉康, 中川 暢彦, 鈴木 雄之典, 山中 雅也, 清水 大, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 5   2021.4

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  13. Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue. International journal

    Yuki Sunagawa, Suguru Yamada, Fuminori Sonohara, Keisuke Kurimoto, Nobutake Tanaka, Yunosuke Suzuki, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Scientific reports   Vol. 11 ( 1 ) page: 6016 - 6016   2021.3

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    Circular RNA (circRNA) is a type of non-coding RNA known to affect cancer-related micro RNAs and various transcription factors. circRNA has promise as a cancer-related biomarker because its circular structure affords high stability. We found using high-throughput sequencing that seven candidate circRNAs (hsa_circ_0041150, hsa_circ_0025624, hsa_circ_0001020, hsa_circ_0028129, hsa_circ_0008558, hsa_circ_0036683, hsa_circ_0058087) were downregulated in HCC. The expression of these circRNAs was examined by quantitative PCR in 233 sets of HCC and matched background normal liver tissues, and correlations between candidate circRNA expression and prognosis were evaluated. The results of quantitative PCR showed that expression of hsa_circ_0041150, hsa_circ_0001020 and hsa_circ_0008558 was significantly lower in HCC than in background normal liver tissues. Kaplan-Meier analysis revealed that low expression of hsa_circ_0001020, hsa_circ_0036683, and hsa_circ_0058087 was associated with poor recurrence-free (RFS) and overall survival (OS) in HCC. Additionally, multivariate analysis revealed that low hsa_circ_0036683 expression was a significant prognostic factor, independent from other clinicopathological features, for inferior RFS and OS. There was no significant association between the expression of these circRNAs and hepatitis B/C status or cirrhosis. This study therefore identified circRNAs as potential prognostic markers for patients who undergo curative surgery for HCC and highlighted hsa_circ_0036683 as the most useful biomarker.

    DOI: 10.1038/s41598-021-85237-y

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  14. Age-Related Differences in the Prognosis of Pancreatic Cancer According to Perioperative Systemic Therapy. International journal

    Fuminori Sonohara, Suguru Yamada, Keisuke Kurimoto, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Tsutomu Fujii, Yasuhiro Kodera

    Pancreas   Vol. 50 ( 1 ) page: 37 - 46   2021.1

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    OBJECTIVES: In this study, we retrospectively assessed the feasibility and prognostic efficacy of perioperative chemo(radio)therapy for pancreatic cancer (PC) patients according to age. METHODS: A total of 556 consecutive patients who underwent curative-intent pancreatectomy for PC between 2000 and 2018 were enrolled. RESULTS: Of the 556 patients who underwent resection, 95 (17%) were elderly (age, ≥75 years). Postoperative complications did not significantly differ between the 2 age groups, and postoperative prognoses were also similar (recurrence-free survival [RFS], P = 0.68; overall survival [OS], P = 0.28). In this cohort, 103 patients (19%) underwent preoperative chemo(radio)therapy, and 417 (77%) underwent postoperative chemotherapy. Perioperative therapy was found to be significantly beneficial for younger patients (preoperative therapy: RFS, P = 0.006; OS, P < 0.001; postoperative therapy: RFS, P < 0.001; OS, P < 0.001). Conversely, no significant survival benefit of perioperative therapy was found for the elderly (preoperative therapy: RFS, P = 0.28; OS, P = 0.44; postoperative therapy: RFS, P = 0.77; OS, P = 0.08). CONCLUSIONS: This study demonstrated that, although perioperative therapy is feasible for selected elderly patients with PC, this approach might not be as beneficial as it is for younger PC patients.

    DOI: 10.1097/MPA.0000000000001712

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  15. Difference Between Educational Law and the Present Status of Continuing Education of High School-Aged Patients with Cancer

    Ozawa Miwa, Maeda Naoko, Mori Makiko, Kurimoto Keisuke, Tsuchiya Miyako, Horibe Keizo

    PEDIATRIC BLOOD & CANCER   Vol. 67   2020.12

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  16. ゲノムワイドアプローチによる肝細胞癌関連circRNAの探索

    砂川 祐輝, 山田 豪, 園原 史訓, 栗本 景介, 猪川 祥邦, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: P219 - 4   2020.12

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  17. 膵臓 化学療法

    砂川 祐輝, 山田 豪, 山中 雅也, 鈴木 雄之典, 中川 暢彦, 加藤 吉康, 田中 伸孟, 栗本 景介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会雑誌   Vol. 53 ( Suppl.2 ) page: 311 - 311   2020.11

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  18. 大腸癌初回肝転移手術後の早期再発予測因子の検討

    林 真路, 山田 豪, 高見 秀樹, 猪川 祥邦, 園原 史訓, 砂川 祐輝, 田中 伸孟, 栗本 景介, 加藤 吉康, 中川 暢彦, 鈴木 雄之典, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 4   2020.8

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  19. 膵頸部癌における臨床病理学的特徴

    栗本 景介, 山田 豪, 鈴木 雄之典, 中川 暢彦, 加藤 吉康, 田中 伸孟, 砂川 祐輝, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 3   2020.8

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  20. 膵頭部癌における周術期輸血の長期予後に対する影響

    田中 伸孟, 山田 豪, 栗本 景介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 3   2020.8

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  21. 膵頭十二指腸切除術施行膵癌患者における周術期メインおよびリパクレオン投与の安全性と有用性

    中川 暢彦, 山田 豪, 多代 充, 栗本 景介, 園原 史訓, 清水 大, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 5   2020.8

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  22. 膵癌に対する膵頭十二指腸切除術の分子生物学的なsurgical marginの評価

    砂川 祐輝, 山田 豪, 林 真路, 高見 秀樹, 猪川 祥邦, 園原 史訓, 栗本 景介, 田中 伸孟, 加藤 吉康, 中川 暢彦, 鈴木 雄之典, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 2   2020.8

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  23. 進行膵癌におけるオリゴメタスタシス症例の検討

    林 真路, 山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 田中 伸孟, 加藤 吉康, 中川 暢彦, 栗本 景介, 鈴木 雄之典, 山中 雅也, 小寺 泰弘

    膵臓   Vol. 35 ( 3 ) page: A304 - A304   2020.7

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  24. 胃原発mixed adenoneuroendocrine carcinomaの1例

    荘加 道太, 清水 大, 栗本 景介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 山田 豪, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器病学会東海支部例会プログラム抄録集   Vol. 131回   page: 59 - 59   2019.11

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    Language:Japanese   Publisher:日本消化器病学会-東海支部  

  25. 日本のAYA世代のがん対策の方向性を読み解く Reviewed

    栗本 景介, 堀部 敬三, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 小林 大介, 田中 千恵, 山田 豪, 中山 吾郎, 小池 聖彦, 清水 千佳子, 高橋 義行, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 57回   page: P166 - 5   2019.10

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    Language:English   Publisher:(一社)日本癌治療学会  

  26. Identification of a serum-based miRNA signature for response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy. Reviewed

    Niwa Y, Yamada S, Sonohara F, Kurimoto K, Hayashi M, Tashiro M, Iwata N, Kanda M, Tanaka C, Kobayashi D, Nakayama G, Koike M, Fujiwara M, Kodera Y

    Journal of translational medicine   Vol. 17 ( 1 ) page: 1   2019.1

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  27. PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma Reviewed

    Keisuke Kurimoto, Masamichi Hayashi, Rafael Guerrero-Preston, Masahiko Koike, Mitsuro Kanda, Sho Hirabayashi, Hiroshi Tanabe, Nao Takano, Naoki Iwata, Yukiko Niwa, Hideki Takami, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Hiroyuki Sugimoto, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera

    EPIGENETICS   Vol. 12 ( 10 ) page: 865 - 874   2017

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:TAYLOR & FRANCIS INC  

    Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001-2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. PAX5 methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0-136.3) in ESCCs and 0.3 (0-8.6) in adjacent normal tissues (P &lt; 0.001). The 78 cases were divided into high QMSP value (high QMSP, n D 26) and low QMSP value (low QMSP, n D 52). High QMSP cases were significantly associated with downregulated PAX5 expression (P D 0.040), and showed significantly poor recurrencefree survival [Hazard Ratio (HR) D 2.84; P D 0.005; 95% Confidence Interval (CI): 1.39-5.81] and overall survival (HR D 3.23; P D 0.002; 95% CI: 1.52-7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. PAX5 gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.

    DOI: 10.1080/15592294.2017.1365207

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KAKENHI (Grants-in-Aid for Scientific Research) 1

  1. 高齢消化器癌手術症例における術後自立度低下に関するリスク評価と介入の有効性の検討

    Grant number:21K11620  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(C)

    田中 千恵, 神田 光郎, 渡邊 一久, 小寺 泰弘, 室谷 健太, 栗本 景介, 藤原 道隆, 中西 香企

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    Authorship:Coinvestigator(s) 

    本研究は,消化器癌における様々な術式の自立度への影響と複数の診療科を含む多職種横断的な介入の効果を包括的に把握し,高齢者に対する癌治療のエビデンス構築の一助となるデータを構築することを目的とする。まず,術前後の自立度の変化について調査票と血清バイオマーカー値の両面から評価する。次に,自立度が低下する患者については,老年科専門医・リハビリテーション・栄養サポートチームによる介入で機能維持を図り,ひいては,事前に自立度が低下する群を予測し,予防的介入が可能となることを見込む。
    これまでの研究で、少ない症例数における解析ではあるが、術後に自立度が低下する群が存在する可能性が示唆されていた。このため本研究では、消化器癌における様々な術式の自立度への影響と複数の診療科を含む多職種横断的な介入の効果を包括的に把握し、高齢者に対する癌治療のエビデンス構築の一助となるデータを構築することを目的としている。
    本年度は、術前、退院時、術後6ヶ月に自立度の調査を行い、症例の集積を進めた。胃癌患者に対する周術期高齢者機能評価は、約65例の症例を集積し、解析が可能な症例数を得た。このため次年度は、自立度に影響を及ぼすリスク因子を抽出することで、周術期自立度の低下に関わる、より詳細な情報を得る予定である。さらに、本年度は75歳以上の胃癌を有する高齢者に対して胃切除術を行った患者を対象として、老年科専門医による評価および術後早期の理学療法士によるリハビリテーションの導入を開始している。次年度以降も症例の集積を進める。以上により、介入による有効性を評価することを計画しているが、介入の有効性、あるいは抽出したリスク症例に対する介入の有効性に関しては、現時点で介入効果が不明であるため、研究分担者である統計家と密に相談しながら、評価を行う。
    また、自立度が低下した症例群と維持された症例群の2群において、自立度のバイオマーカーの探索を開始している。現在、自立度が維持された症例と低下した両群の症例の術前血清を用いて、網羅的なたんぱく質の同定および比較定量を行っている。この結果を元に、次年度はより詳細な検討を予定している。
    これまでの研究で、周術期に高齢者機能評価を行い、ADLが低下する症例群が存在することがわかっている。令和4年度はさらに症例を集積し、自立度が低下するリスク因子を抽出する予定である。
    今後、自立度の影響を及ぼすリスク因子を抽出する予定である。さらに、周術期に老年科専門医による評価および理学療法士によるリハビリテーションを行った症例の集積を進め、その有効性を評価する予定である。さらに、自立度に関わる詳細なバイオマーカー探索を行う。