Faculty Profiles - KURIMOTO Keisuke

特集ハイボリュームセンターのオペ記事《消化管癌編》胃癌噴門側胃切除術のオペ記事-当科におけるロボット支援下噴門側胃切除術

CiNii Research

田中千恵, 杉田静紀, 中西香企, 栗本景介, 小寺泰弘

臨床外科 Vol. 78 ( 13 ) page： 1464 - 1468 2023.12

【ハイボリュームセンターのオペ記事《消化管癌編》】胃癌噴門側胃切除術のオペ記事当科におけるロボット支援下噴門側胃切除術

田中千恵, 杉田静紀, 中西香企, 栗本景介, 小寺泰弘

臨床外科 Vol. 78 ( 13 ) page： 1464 - 1468 2023.12

Predictive impacts of peritoneal washing cytology for surgical resection-intended pancreatic cancer cases: Establishment of planned staging laparoscopy criteria

Tanaka, N; Takami, H; Hayashi, M; Inokawa, Y; Kurimoto, K; Hattori, N; Kanda, M; Tanaka, C; Nakayama, G; Kodera, Y

JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES Vol. 30 ( 11 ) page： 1273 - 1281 2023.11

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

Background: Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real-world clinical data about CY status-depending surgical outcomes should be accumulated. Methods: Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020. Correlations between the CY status and other clinicopathological parameters with the recurrence patterns and survival outcomes were examined. In addition, we analyzed several risk factors for the CY+ status and attempted to identify the patient population that may benefit most from SL. Results: A total of 24 of the 183 patients were CY+. Peritoneal recurrence occurred more frequently in CY+ cases than in CY− cases (29% vs. 6%, p <.001) and median survival time after surgery was significantly shorter in CY+ cases than in CY− cases (28.5 months vs. 67.5 months; p <.001). In detail, almost all CY+ patients among curative resection-intended cases had either elevated preoperative serum CA19-9 levels (≥250 U/mL) or DUPAN-2 levels (≥150 U/mL). Significant predictive factors of CY positivity were BR status (p =.028) and serum CA19-9 level exceeding 250 U/mL (p =.008). Conclusion: CY status was identified as an independent prognostic factor, and SL examination should be recommended, especially for patients with risk factors for CY positivity, such as BR cancer and elevated serum CA19-9 levels.

DOI： 10.1002/jhbp.1373

High Preoperative Serum D-dimer Predicts Unfavorable Survival Outcomes for Pancreatic Cancer Patients. International journal

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

Anticancer research Vol. 43 ( 7 ) page： 3173 - 3181 2023.7

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

BACKGROUND/AIM: Pancreatic cancer cells release certain tissue factors into the bloodstream. It is well known that pancreatic cancer progresses with thrombus formation. Because we routinely measure serum D-dimer levels in preoperative patients as a screening marker of deep venous thrombosis, we examined its association with high serum D-dimer in our cohort of pancreatic cancer resected cases. PATIENTS AND METHODS: We examined 315 patients with pancreatic ductal adenocarcinoma who underwent surgical resection in our department from January 2012 to July 2021. All cases were divided into high D-dimer cases (n=118) and low D-dimer cases (n=197) using the cut-off value of 1.0 μg/ml, an institutional upper limit. Clinicohistological characteristics and postoperative survival outcomes were evaluated. RESULTS: Preoperative high D-dimer cases showed significantly worse progression-free survival (PFS) (p=0.021) and overall survival (OS) (p=0.027) than low D-dimer cases; median PFS was 13.9 months versus 21.4 months, and that of OS was 33.4 months versus 68.0 months. Clinicohistological characteristics of high D-dimer cases were age over 70 years (p<0.001), pathological portal vein invasion (p=0.003), and initially borderline resectable or unresectable cases (p=0.027). Multivariate analysis indicated that preoperative high D-dimer was a significant prognostic factor of PFS (hazard ratio=1.42, p=0.025) and OS (hazard ratio=1.51, p=0.036). CONCLUSION: Preoperative high serum D-dimer over 1.0 μg/ml was associated with pathological portal vein invasion and could be an unfavorable prognostic marker of PFS and OS after surgery, typically due to distant metastasis.

DOI： 10.21873/anticanres.16491

Albumin-Globulin Ratio Indicates the Survival Outcome of Pancreatic Cancer Cases Who Underwent Preoperative Treatment and Curative Surgical Resection. International journal

Masamichi Hayashi, Daigo Kobayashi, Hideki Takami, Yoshikuni Inokawa, Nobutake Tanaka, Keisuke Kurimoto, Koki Nakanishi, Shinichi Umeda, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Yasuhiro Kodera

Nutrition and cancer Vol. 75 ( 5 ) page： 1330 - 1339 2023.5

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

BACKGROUND: The pretreatment albumin-globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies. METHODS: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-globulin ratio (AGR) were calculated for each case. RESULTS: Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases (P = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases (P = 0.043). CONCLUSION: High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

DOI： 10.1080/01635581.2023.2191384

切除可能・切除可能境界型膵癌に対する腹腔洗浄細胞診の意義と治療戦略

田中伸孟, 高見秀樹, 栗本景介, 林真路, 中西香企, 梅田晋一, 清水大, 服部憲史, 神田光郎, 田中千恵, 中山吾郎, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 123回 page： SF - 4 2023.4

膵IPMN切除後予後に関連する因子および術後補助療法の影響に関する検討

猪川祥邦, 高見秀樹, 栗本景介, 田中伸孟, 林真路, 中西香企, 梅田晋一, 清水大, 服部憲史, 神田光郎, 田中千恵, 中山吾郎, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 123回 page： DP - 5 2023.4

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

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

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

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

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

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

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

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

Otsu, T; Inokawa, Y; Takami, H; Hayashi, M; Kurimoto, K; Tanaka, N; Tanaka, H; Shimizu, D; Hattori, N; Kanda, M; Tanaka, C; Nakayama, G; Kodera, Y

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

Language：English Publisher：Anticancer Research

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

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

Satoi, S; Takahara, N; Fujii, T; Isayama, H; Yamada, S; Tsuji, Y; Miyato, H; Yamaguchi, H; Yamamoto, T; Hashimoto, D; Yamaki, S; Nakai, Y; Saito, K; Baba, H; Watanabe, T; Ishii, S; Hayashi, M; Kurimoto, K; Shimada, H; Kitayama, J

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

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

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

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

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

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

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

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

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

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