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Pancreatic Neoplasms: HELP
Articles by Naminatsu Takahara
Based on 31 articles published since 2010
(Why 31 articles?)
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Between 2010 and 2020, N. Takahara wrote the following 31 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Covered versus uncovered metal stents for malignant gastric outlet obstruction: Systematic review and meta-analysis. 2017

Hamada, Tsuyoshi / Hakuta, Ryunosuke / Takahara, Naminatsu / Sasaki, Takashi / Nakai, Yousuke / Isayama, Hiroyuki / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA. · Department of Gastroenterology, Japanese Red Cross Medical Center, Tokoyo, Japan. · Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. ·Dig Endosc · Pubmed #27997723.

ABSTRACT: BACKGROUND AND AIM: Self-expandable metal stents (SEMS) are used for non-resectable malignant gastric outlet obstruction (GOO). Studies of covered versus uncovered SEMS have yielded inconsistent results as a result of heterogeneity in design and patient population. We carried out a meta-analysis to compare covered and uncovered gastroduodenal SEMS. METHODS: Using MEDLINE, Embase, and the Cochrane database, we identified 1624 patients from 13 prospective and retrospective studies that evaluated covered and uncovered SEMS for malignant GOO and were published until October 2016. We pooled data on SEMS dysfunction, technical and clinical success, and adverse events using the fixed-effect or random-effects model. RESULTS: Compared with uncovered SEMS, covered SEMS did not show any significant difference in stent dysfunction risk (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.79-1.32). A subgroup analysis of five randomized trials suggested a trend toward a lower dysfunction risk in covered SEMS (RR, 0.63; 95% CI, 0.45-0.88). Covered SEMS were associated with a lower occlusion risk (RR, 0.44; 95% CI, 0.28-0.68), but with a higher migration risk (RR, 4.28; 95% CI, 2.89-6.34). Technical and clinical success rates were comparable between the groups. Overall adverse events tended to be more frequent in covered SEMS (RR, 1.75; 95% CI, 1.09-2.83). CONCLUSIONS: Outcomes of covered and uncovered gastroduodenal SEMS were comparable, although the lower dysfunction rate of covered SEMS observed in the analysis of randomized trials needs further investigation. Antimigration mechanisms for covered SEMS and identification of patients who can achieve longer patency from uncovered SEMS would help improve the outcomes of gastroduodenal SEMS.

2 Review Progression-free survival as a surrogate for overall survival in first-line chemotherapy for advanced pancreatic cancer. 2016

Hamada, Tsuyoshi / Nakai, Yousuke / Isayama, Hiroyuki / Yasunaga, Hideo / Matsui, Hiroki / Takahara, Naminatsu / Mizuno, Suguru / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: hamada-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: ynakai-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: isayama-tky@umin.ac.jp. · Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. Electronic address: yasunagah-tky@umin.ac.jp. · Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. Electronic address: ptmatsui-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: naminatsu.takahara@gmail.com. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: smizuno-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: kogureh-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: sab-tky@umin.net. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: natsuyoy-gi@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: mtada-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: kkoike-tky@umin.ac.jp. ·Eur J Cancer · Pubmed #27451020.

ABSTRACT: BACKGROUND: Overall survival (OS), as the primary end-point in first-line chemotherapy trials, requires a prolonged follow-up time and may be confounded by subsequent regimens. This study aimed to evaluate the correlation between OS and surrogate end-points (progression-free survival [PFS], response rate and disease control rate), and to identify a potential surrogate for OS in advanced pancreatic cancer. METHODS: Based on an electronic search, we identified randomized controlled phase II and III trials of first-line chemotherapy for advanced pancreatic cancer. Correlation analyses were performed between surrogate end-points and OS, and between improvements in surrogates and those in OS. RESULTS: Fifty trials (II/II-III/III, 17/2/31) with 111 treatment arms were identified, and 15,906 patients were analysed. PFS was most strongly correlated with OS (correlation coefficient, 0.76). Weighted linear regression models revealed the greatest determinant coefficient of 0.84 between the hazard ratio (HR) of the experimental arms compared with the control arms of PFS and that of OS. The approximate equation was log HROS = 0.01 + 0.77 × log HRPFS, indicating that risk reduction of OS via chemotherapy would translate into a 77% risk reduction of PFS. The surrogacy of PFS for OS was robust throughout our subgroup analyses: e.g., biologic versus non-biologic regimens, locally advanced versus metastatic disease. CONCLUSIONS: The surrogacy of PFS for OS in pancreatic cancer was validated. Therefore, the use of PFS as the primary end-point in clinical trials could facilitate the early introduction of new effective chemotherapy regimens into clinical practice.

3 Clinical Trial A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer. 2019

Saito, Kei / Isayama, Hiroyuki / Nakai, Yousuke / Takahara, Naminatsu / Ishigaki, Kazunaga / Takeda, Tsuyoshi / Hakuta, Ryunosuke / Saito, Tomotaka / Uchino, Rie / Kishikawa, Takahiro / Hamada, Tsuyoshi / Mizuno, Suguru / Sasaki, Takashi / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. isayama-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan. isayama-tky@umin.ac.jp. ·Invest New Drugs · Pubmed #30411217.

ABSTRACT: Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4-13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3-4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.

4 Clinical Trial A phase II trial of gemcitabine, S-1 and LV combination (GSL) neoadjuvant chemotherapy for patients with borderline resectable and locally advanced pancreatic cancer. 2018

Saito, Kei / Isayama, Hiroyuki / Sakamoto, Yoshihiro / Nakai, Yousuke / Ishigaki, Kazunaga / Tanaka, Mariko / Watadani, Takeyuki / Arita, Junichi / Takahara, Naminatsu / Mizuno, Suguru / Kogure, Hirofumi / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Hasegawa, Kiyoshi / Fukayama, Masashi / Kokudo, Norihiro / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. isayama-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan. isayama-tky@umin.ac.jp. · Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Med Oncol · Pubmed #29846849.

ABSTRACT: There has been a pressing need to develop optimal regimen for neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). The safety and efficacy of gemcitabine, S-1, and LV combination (GSL) therapy as NAC for borderline resectable (BR) and locally advanced (LA) PC was evaluated in this phase II study. Patients with pathologically proven BR or LA PC were enrolled and gemcitabine 1000 mg/m

5 Clinical Trial Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis. 2017

Satoi, Sohei / Fujii, Tsutomu / Yanagimoto, Hiroaki / Motoi, Fuyuhiko / Kurata, Masanao / Takahara, Naminatsu / Yamada, Suguru / Yamamoto, Tomohisa / Mizuma, Masamichi / Honda, Goro / Isayama, Hiroyuki / Unno, Michiaki / Kodera, Yasuhiro / Ishigami, Hironori / Kon, Masanori. ·*Department of Surgery, Kansai Medical University †Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine ‡Department of Surgery, Tohoku University Graduate School of Medicine §Department of Surgery, University of Tsukuba ¶Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo ||Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital **Department of Chemotherapy, the University of Tokyo. ·Ann Surg · Pubmed #28059968.

ABSTRACT: OBJECTIVE: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. BACKGROUND: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. METHODS: Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). RESULTS: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. CONCLUSIONS: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

6 Clinical Trial Intravenous and intraperitoneal paclitaxel with S-1 for treatment of refractory pancreatic cancer with malignant ascites. 2016

Takahara, Naminatsu / Isayama, Hiroyuki / Nakai, Yousuke / Ishigami, Hironori / Satoi, Sohei / Mizuno, Suguru / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Yamaguchi, Hironori / Tada, Minoru / Kitayama, Joji / Watanabe, Toshiaki / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. isayama-tky@umin.ac.jp. · Department of Chemotherapy, The University of Tokyo, Tokyo, Japan. · Department of Surgery, Kansai Medical University, Osaka, Japan. · Department of Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan. · Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan. ·Invest New Drugs · Pubmed #27339809.

ABSTRACT: CLINICAL TRIAL REGISTRATION NUMBER: UMIN000005306).

7 Clinical Trial A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer. 2014

Nakai, Yousuke / Isayama, Hiroyuki / Saito, Kei / Sasaki, Takashi / Takahara, Naminatsu / Hamada, Tsuyoshi / Mizuno, Suguru / Miyabayashi, Koji / Yamamoto, Keisuke / Mohri, Dai / Kogure, Hirofumi / Yamamoto, Natsuyo / Hirano, Kenji / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. ·Cancer Chemother Pharmacol · Pubmed #25143299.

ABSTRACT: PURPOSE: In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL). METHODS: Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m(2) over 30 min on day 1, and oral S-1 at a dose of 40 mg/m(2) twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. A standard "3 + 3" phase I dose escalation design was utilized. RESULTS: Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥ 50 % decline. CONCLUSIONS: RD of gemcitabine in GSL was determined as 1,000 mg/m(2). GSL was well tolerable and showed promising results in advanced pancreatic cancer.

8 Clinical Trial Intravenous and intraperitoneal paclitaxel with S-1 for refractory pancreatic cancer with malignant ascites: an interim analysis. 2014

Takahara, Naminatsu / Isayama, Hiroyuki / Nakai, Yousuke / Sasaki, Takashi / Ishigami, Hironori / Yamashita, Hiroharu / Yamaguchi, Hironori / Hamada, Tsuyoshi / Uchino, Rie / Mizuno, Suguru / Miyabayashi, Koji / Mohri, Dai / Kawakubo, Kazumichi / Kogure, Hirofumi / Yamamoto, Natsuyo / Sasahira, Naoki / Hirano, Kenji / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Kitayama, Joji / Watanabe, Toshiaki / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, , Bunkyo-ku, Tokyo, 113-8655, Japan. ·J Gastrointest Cancer · Pubmed #24676891.

ABSTRACT: OBJECTIVES: Here, we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites. METHODS: Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7-day rest. RESULTS: Between April 2011 and February 2012, ten patients were enrolled. A partial response was achieved in two patients (20%) and a disease control rate of 50%. The median time to progression and overall survival were 2.1 and 3.4 months, respectively. Malignant ascites was completely resolved in two patients (20%). Major grade 3/4 adverse events were myelosuppression including neutropenia (50%) and catheter-related infection (10%). CONCLUSIONS: This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites (clinical trial registration number: UMIN000005306).

9 Clinical Trial A multicenter phase II trial of gemcitabine and candesartan combination therapy in patients with advanced pancreatic cancer: GECA2. 2013

Nakai, Yousuke / Isayama, Hiroyuki / Ijichi, Hideaki / Sasaki, Takashi / Takahara, Naminatsu / Ito, Yukiko / Matsubara, Saburo / Uchino, Rie / Yagioka, Hiroshi / Arizumi, Toshihiko / Hamada, Tsuyoshi / Miyabayashi, Koji / Mizuno, Suguru / Yamamoto, Keisuke / Kogure, Hirofumi / Yamamoto, Natsuyo / Hirano, Kenji / Sasahira, Naoki / Tateishi, Keisuke / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, Japan, 113-8655. ·Invest New Drugs · Pubmed #23690239.

ABSTRACT: BACKGROUND: Our retrospective study and phase I trial of gemcitabine and candesartan combination therapy suggested the inhibition of renin-angiotensin system potentially has a role in the treatment of advanced pancreatic cancer. The aim of this multicenter phase II trial was to assess the efficacy and toxicity of gemcitabine and candesartan combination therapy for advanced pancreatic cancer. METHODS: Chemotherapy-naive patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m(2) over 30 min on days 1, 8, and 15 and oral candesartan at a dose of 16 mg in normotensive patients, and 8 mg initially in hypertensive patients, with dose escalation to 16 mg allowed, from days 1 to 28, repeated every 4 weeks. RESULTS: A total of 35 patients with advanced pancreatic cancer were enrolled. Overall response rate and disease control rate were 11.4 % and 62.9 %. The median PFS and OS were 4.3 and 9.1 months with 1-year survival rate of 34.2 %. The median PFS was significantly longer in patients receiving 16 mg compared with 8 mg of candesartan (4.6 vs. 3.5 months, p=0.031). Major severe toxicities were neutropenia (23 %), leukopenia (17 %) and thrombocytopenia (11 %). Grade 2 hypotension was observed in 3 patients (9 %) and candesartan was discontinued in 2 patients due to hypotension. Conclusions In this multicenter phase 2 trial, gemcitabine and candesartan combination therapy was tolerable but failed to demonstrate activity against advanced pancreatic cancer. (UMIN CTR: UMIN000005580).

10 Clinical Trial Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer. 2013

Takahara, Naminatsu / Nakai, Yousuke / Isayama, Hiroyuki / Sasaki, Takashi / Satoh, Yumiko / Takai, Daiya / Hamada, Tsuyoshi / Uchino, Rie / Mizuno, Suguru / Miyabayashi, Koji / Mohri, Dai / Kawakubo, Kazumichi / Kogure, Hirofumi / Yamamoto, Natsuyo / Sasahira, Naoki / Hirano, Kenji / Ijichi, Hideaki / Tada, Minoru / Yatomi, Yutaka / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Cancer Chemother Pharmacol · Pubmed #23053265.

ABSTRACT: PURPOSE: The aim of this study was to evaluate the efficacy and safety of irinotecan monotherapy in patients with advanced pancreatic cancer (APC). METHODS: Patients with APC refractory to gemcitabine and S-1 were included. Irinotecan (100 mg/m(2)) was administered on days 1, 8, and 15 every 4 weeks until disease progression or unacceptable toxicity was observed. The relationship between uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms and clinical outcomes was evaluated. RESULTS: Between January 2007 and December 2011, 231 cycles were delivered in 56 patients. Irinotecan was administered as second-line chemotherapy in 35.7% of patients and as third-line chemotherapy or later in 64.3%. A partial response was achieved in two (3.6%) and stable disease in 23 patients (41.0%), giving a disease control rate of 44.6%. The median time to progression (TTP) and overall survival (OS) were 2.9 (95% confidence interval [CI] 1.8-3.5) months and 5.3 (95% CI 4.5-6.8) months, respectively. Median survival from the first-line chemotherapy was 19.5 (95% CI 15.3-23.8) months. Major grade 3/4 adverse events included neutropenia (28.6%), anemia (12.5%), and anorexia (10.7%). Patients with *6 and/or *28 allele(s) (n = 15) were associated with grade 3/4 neutropenia and anorexia but showed longer TTP (5.3 vs. 1.8 months; p = 0.05), and OS (8.0 vs. 4.8 months; p = 0.09) than those without *6 and/or *28 (n = 29). CONCLUSIONS: Salvage chemotherapy with irinotecan was moderately effective and well-tolerated in patients with APC refractory to gemcitabine and S-1. UGT1A1 polymorphisms were associated with toxicity and efficacy.

11 Article Long-term Risk of Malignancy in Branch-Duct Intraductal Papillary Mucinous Neoplasms. 2020

Oyama, Hiroki / Tada, Minoru / Takagi, Kaoru / Tateishi, Keisuke / Hamada, Tsuyoshi / Nakai, Yousuke / Hakuta, Ryunosuke / Ijichi, Hideaki / Ishigaki, Kazunaga / Kanai, Sachiko / Kogure, Hirofumi / Mizuno, Suguru / Saito, Kei / Saito, Tomotaka / Sato, Tatsuya / Suzuki, Tatsunori / Takahara, Naminatsu / Morishita, Yasuyuki / Arita, Junichi / Hasegawa, Kiyoshi / Tanaka, Mariko / Fukayama, Masashi / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: mtada-tky@umin.ac.jp. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan. · Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Hepato-Pancreatico-Biliary Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Gastroenterology · Pubmed #31473224.

ABSTRACT: BACKGROUND & AIMS: Long-term outcomes of patients with branch-duct intraductal papillary mucinous neoplasms (IPMNs), particularly those after 5 years of surveillance, have not been fully evaluated in large studies. We analyzed incidences of IPMN-derived carcinoma and concomitant ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]) over 20 years in a large population of patients. METHODS: We identified 1404 consecutive patients (52% women; mean age, 67.5 years) with a diagnosis of branch-duct IPMN, from 1994 through 2017, at the University of Tokyo in Japan. Using a competing risk analysis, we estimated cumulative incidence of pancreatic carcinoma, overall and by carcinoma type. We used competing risks proportional hazards models to estimate subdistribution hazard ratios (SHRs) for incidences of carcinomas. To differentiate IPMN-derived and concomitant carcinomas, we collected genomic DNA from available paired samples of IPMNs and carcinomas and detected mutations in GNAS and KRAS by polymerase chain reaction and pyrosequencing. RESULTS: During 9231 person-years of follow-up, we identified 68 patients with pancreatic carcinomas (38 patients with IPMN-derived carcinomas and 30 patients with concomitant PDACs); the overall incidence rates were 3.3%, 6.6%, and 15.0% at 5, 10, and 15 years, respectively. Among 804 patients followed more than 5 years, overall cumulative incidence rates of pancreatic carcinoma were 3.5% at 10 years and 12.0% at 15 years from the initial diagnosis. The size of the IPMN and the diameter of the main pancreatic duct associated with incidence of IPMN-derived carcinoma (SHR 1.85; 95% confidence interval 1.38-2.48 for a 10-mm increase in the IPMN size and SHR 1.56; 95% confidence interval 1.33-1.83 for a 1-mm increase in the main pancreatic duct diameter) but not with incidence of concomitant PDAC. CONCLUSIONS: In a large long-term study of patients with branch-duct IPMNs, we found the 5-year incidence rate of pancreatic malignancy to be 3.3%, reaching 15.0% at 15 years after IPMN diagnosis. We observed heterogeneous risk factor profiles between IPMN-derived and concomitant carcinomas.

12 Article Current Status of Endoscopic Ultrasound Techniques for Pancreatic Neoplasms. 2019

Nakai, Yousuke / Takahara, Naminatsu / Mizuno, Suguru / Kogure, Hirofumi / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Clin Endosc · Pubmed #31337194.

ABSTRACT: Endoscopic ultrasound (EUS) now plays an important role in the management of pancreatic neoplasms. There are various types of pancreatic neoplasms, from benign to malignant lesions, and the role of EUS ranges from the imaging diagnosis to treatment. EUS is useful for the detection, characterization, and tissue acquisition of pancreatic lesions. Recent advancement of contrast-enhanced harmonic EUS and elastography enables better characterization of pancreatic lesions. In addition to these enhanced EUS imaging techniques, EUS-guided tissue acquisition is now the standard procedure to establish the pathological diagnosis of pancreatic neoplasms. While these diagnostic roles of EUS have been established, EUS-guided interventions such as ablation and drainage are also increasingly utilized in the management of pancreatic neoplasms. However, most of these EUS-guided interventions are not yet standardized in terms of techniques and devices and thus need further investigations.

13 Article Diagnostic yield of the plasma free amino acid index for pancreatic cancer in patients with diabetes mellitus. 2019

Mizuno, Suguru / Isayama, Hiroyuki / Nakai, Yousuke / Ishigaki, Kazunaga / Saito, Kei / Sato, Tatsuya / Takeda, Tsuyoshi / Hakuta, Ryunosuke / Saito, Tomotaka / Takahara, Naminatsu / Kogure, Hirofumi / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Shikata, Nahoko / Tagami, Tomoyuki / Kikuchi, Shinya / Yamamoto, Hiroshi / Yamakado, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan. Electronic address: isayama-tky@umin.ac.jp. · Research Institute for Bioscience Products & Fine Chemicals, Ajinomoto Co., Inc., Kanagawa, Japan. · Department of Nursing, Ashikaga University, Tochigi, Japan; Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Tokyo, Japan. ·Pancreatology · Pubmed #31320196.

ABSTRACT: OBJECTIVES: A multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. METHODS: We compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. RESULTS: A total of 180 case-control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). CONCLUSIONS: This matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

14 Article A Multicenter Open-Label Randomized Controlled Trial of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer. 2018

Saito, Tomotaka / Nakai, Yousuke / Isayama, Hiroyuki / Hirano, Kenji / Ishigaki, Kazunaga / Hakuta, Ryunosuke / Takeda, Tsuyoshi / Saito, Kei / Umefune, Gyotane / Akiyama, Dai / Watanabe, Takeo / Takagi, Kaoru / Takahara, Naminatsu / Hamada, Tsuyoshi / Uchino, Rie / Mizuno, Suguru / Mouri, Dai / Yagioka, Hiroshi / Kogure, Hirofumi / Togawa, Osamu / Matsubara, Saburo / Ito, Yukiko / Yamamoto, Natsuyo / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Tokyo Takanawa Hospital. · Department of Gastroenterology, Japanese Red Cross Medical Center. · Department of Gastroenterology, JR Tokyo General Hospital. · Department of Gastroenterology, Tokyo Metropolitan Police Hospital. · Department of Gastroenterology, Kanto Central Hospital. · Department of Gastroenterology, Toshiba General Hospital, Tokyo, Japan. ·Pancreas · Pubmed #29851751.

ABSTRACT: OBJECTIVE: Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients. METHODS: Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival. RESULTS: A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070). CONCLUSIONS: In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

15 Article Thromboembolisms in Advanced Pancreatic Cancer: A Retrospective Analysis of 475 Patients. 2017

Ishigaki, Kazunaga / Nakai, Yousuke / Isayama, Hiroyuki / Saito, Kei / Hamada, Tsuyoshi / Takahara, Naminatsu / Mizuno, Suguru / Mohri, Dai / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Tada, Minoru / Koike, Kazuhiko. ·From the Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Pancreas · Pubmed #28787333.

ABSTRACT: OBJECTIVES: Pancreatic cancer is reported to be highly associated with thromboembolism (TE). The aim of this analysis is to clarify risk factors for TE and its clinical impact in Japanese patients with pancreatic cancer. METHODS: Data on consecutive pancreatic cancer patients receiving systemic chemotherapy between August 1999 and July 2015 were retrospectively studied. Both symptomatic and asymptomatic, arterial and venous TEs were included in the analysis. Risk factors for TE development were analyzed using a proportional hazards model with death without TE as a competing risk. The impact of TE on survival was also evaluated using a time-dependent covariate multiple Cox model. RESULTS: A total of 475 patients were included in the analysis, and 57 TEs (12%) were identified: 45 venous TEs and 12 arterial TEs. The median time to TE was 169 days and the median survival from TE was 65 days. Liver metastasis was the only significant risk factor for TE (subdistribution hazards ratio, 2.15; P = 0.01), and TE was significantly associated with poor prognosis (hazards ratio, 3.31; P < 0.01). CONCLUSIONS: Thromboembolism was not uncommon in Japanese patients receiving chemotherapy for advanced pancreatic cancer and was associated with poor prognosis. Liver metastasis was the risk factor for TE.

16 Article The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study. 2017

Saito, Tomotaka / Hirano, Kenji / Isayama, Hiroyuki / Nakai, Yousuke / Saito, Kei / Umefune, Gyotane / Akiyama, Dai / Watanabe, Takeo / Takagi, Kaoru / Hamada, Tsuyoshi / Takahara, Naminatsu / Uchino, Rie / Mizuno, Suguru / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Tada, Minoru / Koike, Kazuhiko. ·From the *Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo; and †Department of Gastroenterology, Tokyo Takanawa Hospital, Tokyo, Japan. ·Pancreas · Pubmed #28099252.

ABSTRACT: OBJECTIVES: Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy. METHODS: This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups. RESULTS: A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P < 0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131). CONCLUSIONS: The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

17 Article Antireflux Metal Stent as a First-Line Metal Stent for Distal Malignant Biliary Obstruction: A Pilot Study. 2017

Hamada, Tsuyoshi / Isayama, Hiroyuki / Nakai, Yousuke / Togawa, Osamu / Takahara, Naminatsu / Uchino, Rie / Mizuno, Suguru / Mohri, Dai / Yagioka, Hiroshi / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Ito, Yukiko / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterology, Tokyo Metropolitan Police Hospital, Tokyo, Japan. · Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan. ·Gut Liver · Pubmed #27282268.

ABSTRACT: Background/Aims: In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. Methods: Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. Results: In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced nonocclusion cholangitis. Conclusions: The ARMS as a first-line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted.

18 Article [IPMN and pancreatic cyst as high risk of pancreatic cancer]. 2015

Tada, Minoru / Takagi, Kaori / Kawakubo, Kazumichi / Hakuta, Ryunosuke / Ishigaki, Kazunaga / Takeda, Tsuyoshi / Fujiwara, Hiroaki / Umefune, Gyotane / Saito, Kei / Saito, Tomotaka / Watanabe, Takeo / Akiyama, Dai / Uchino, Rie / Kishikawa, Takahiro / Takahara, Naminatsu / Takahashi, Ryota / Yamamoto, Keisuke / Hamada, Tsuyoshi / Mizuno, Suguru / Miyabayashi, Koji / Mohri, Dai / Matsubara, Saburo / Kogure, Hirofumi / Nakai, Yousuke / Yamamoto, Natsuyo / Sasaki, Takashi / Sasahira, Naoki / Hirano, Kenji / Ijichi, Hideaki / Tateishi, Keisuke / Isayama, Hiroyuki / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #26250126.

ABSTRACT: -- No abstract --

19 Article Pancreatic cancer with malignant ascites: clinical features and outcomes. 2015

Takahara, Naminatsu / Isayama, Hiroyuki / Nakai, Yousuke / Sasaki, Takashi / Saito, Kei / Hamada, Tsuyoshi / Mizuno, Suguru / Miyabayashi, Koji / Mohri, Dai / Kogure, Hirofumi / Matsubara, Saburo / Yamamoto, Natsuyo / Hirano, Kenji / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Koike, Kazuhiko. ·From the Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Pancreas · Pubmed #25636085.

ABSTRACT: OBJECTIVES: Malignant ascites (MA) caused by peritoneal carcinomatosis is not uncommon in patients with pancreatic cancer. However, the clinical features and outcomes in these patients remain to be elucidated. METHODS: Baseline characteristics and overall survival (OS) of consecutive patients with advanced pancreatic cancer who presented with MA were retrospectively evaluated. RESULTS: Of 494 patients with advanced pancreatic cancer, 73 (15%) presented with MA. Patients with synchronous MA (n = 21), compared with those with metachronous MA (n = 52), had better performance status (P = 0.02), smaller amount of ascites (P < 0.01), and higher chance of receiving chemotherapy (57% vs 17%, P < 0.01), and resulted in longer OS (115 vs 42 days, P < 0.01). Overall survival was significantly longer in patients receiving chemotherapy than in those with best supportive care alone (124 vs 50 days, P < 0.01). In a multivariate analysis, chemotherapy was prognostic in addition to performance status, CRP, and small amount of MA; the hazard ratio of chemotherapy was 0.46, compared with best supportive care alone (P = 0.02). CONCLUSIONS: Although the prognosis of pancreatic cancer patients with MA remains poor, selected patients may be candidate for chemotherapy, regardless of the timing of appearance of MA.

20 Article Risk factors for post-ERCP pancreatitis in wire-guided cannulation for therapeutic biliary ERCP. 2015

Nakai, Yousuke / Isayama, Hiroyuki / Sasahira, Naoki / Kogure, Hirofumi / Sasaki, Takashi / Yamamoto, Natsuyo / Saito, Kei / Umefune, Gyotane / Akiyama, Dai / Kawahata, Shuhei / Matsukawa, Miho / Saito, Tomotaka / Hamada, Tsuyoshi / Takahara, Naminatsu / Mizuno, Suguru / Miyabayashi, Koji / Mohri, Dai / Hirano, Kenji / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Gastrointest Endosc · Pubmed #25442080.

ABSTRACT: BACKGROUND: Wire-guided cannulation (WGC) was reported to decrease post-ERCP pancreatitis (PEP), but risk factors for PEP in WGC are not fully elucidated. OBJECTIVE: To evaluate the incidence and risk factors of PEP in WGC. DESIGN: Single-center retrospective study. SETTING: Academic center. PATIENTS: A total of 800 consecutive patients with a native papilla. INTERVENTIONS: Biliary therapeutic ERCP by using WGC. MAIN OUTCOME MEASUREMENTS: The rate of PEP and its risk factors. RESULTS: Biliary cannulation was successful by using WGC alone in 70.5%, and the final cannulation rate was 96.1%. Unintentional guidewire insertion and contrast material injection into the pancreatic duct (PD) during cannulation occurred in 55.3% and 21.8%, respectively. The incidence of PEP was 9.5% (mild 5.6%, moderate 2.9%, severe 1.0%). Multivariate analysis revealed a common bile duct (CBD) diameter of <9 mm (odds ratio [OR] 2.03; P = .006) and unintentional guidewire insertion into the PD (OR 2.25; P = .014) as risk factors for PEP. PD opacification was not a risk factor for PEP (OR 1.15; P = .642), but the incremental increase of the PEP rate was seen in patients with CBDs <9 mm: 4.6% without any PD manipulation, 8.3% with contrast material alone, 16.9% with guidewire alone, and 22.1% with both contrast material and guidewire. LIMITATIONS: Retrospective design in a single center. CONCLUSION: Unintentional PD manipulation was not uncommon in WGC. Guidewire insertion into the PD and a small CBD were risk factors for PEP in biliary therapeutic ERCP with the use of WGC.

21 Article The inhibition of renin-angiotensin system in advanced pancreatic cancer: an exploratory analysis in 349 patients. 2015

Nakai, Yousuke / Isayama, Hiroyuki / Sasaki, Takashi / Takahara, Naminatsu / Saito, Kei / Ishigaki, Kazunaga / Hamada, Tsuyoshi / Mizuno, Suguru / Miyabayashi, Koji / Yamamoto, Keisuke / Mohri, Dai / Kogure, Hirofumi / Yamamoto, Natsuyo / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. ·J Cancer Res Clin Oncol · Pubmed #25398651.

ABSTRACT: PURPOSE: The role of local renin-angiotensin system (RAS) as a target for the treatment of pancreatic cancer has been increasingly reported, but the addition of candesartan, one of angiotensin system inhibitors (ASIs), to gemcitabine in our prospective trial failed to demonstrate activity against pancreatic cancer. The aim of this study was to explore subgroups that would benefit from the inhibition of RAS by the use of ASIs. METHODS: Consecutive patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy were retrospectively studied. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated by a Cox proportional hazards model. Interactions between the use of ASIs and each subgroup were tested. RESULTS: Between 2001 and 2013, 349 patients received gemcitabine-based chemotherapy for advanced pancreatic cancer; 232 were metastatic, 210 received gemcitabine monotherapy, 108 took ASIs, 166 were never smokers and 188 were diabetic. The median PFS and OS were 4.9 and 11.2 months, respectively. When the effects of the use of ASIs were evaluated by a Cox proportional hazard model, there were two subgroups with P interaction <0.10 both in PFS and OS: never smokers and gemcitabine monotherapy. HRs for PFS and OS by the inhibition of RAS were 0.71 (P = 0.021) and 0.68 (P = 0.014) in never smokers and 0.70 (P = 0.027) and 0.77 (P = 0.124) in patients receiving gemcitabine monotherapy. CONCLUSION: The inhibition of RAS in advanced pancreatic cancer might improve clinical outcomes in cases without a history of smoking or in cases receiving gemcitabine monotherapy.

22 Article Transmural biliary drainage can be an alternative to transpapillary drainage in patients with an indwelling duodenal stent. 2014

Hamada, Tsuyoshi / Isayama, Hiroyuki / Nakai, Yousuke / Kogure, Hirofumi / Yamamoto, Natsuyo / Kawakubo, Kazumichi / Takahara, Naminatsu / Uchino, Rie / Mizuno, Suguru / Sasaki, Takashi / Togawa, Osamu / Matsubara, Saburo / Ito, Yukiko / Hirano, Kenji / Tsujino, Takeshi / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan, hamada-tky@umin.ac.jp. ·Dig Dis Sci · Pubmed #24839917.

ABSTRACT: BACKGROUND: Self-expandable metal stents (SEMS) are widely utilized to relieve symptoms of malignant gastric outlet obstruction (GOO), but GOO is frequently complicated by nonresectable distal biliary obstruction. The optimal endoscopic approach to biliary drainage in this setting remains controversial and has yet to be resolved. AIMS: To compare the safety and efficacy of endoscopic ultrasound-guided transmural biliary drainage (EUS-BD) and transpapillary drainage in patients with an indwelling duodenal SEMS. METHODS: Patients who underwent EUS-BD or transpapillary drainage for distal malignant biliary obstruction with an indwelling duodenal SEMS between June 2007 and August 2012 at three Japanese tertiary referral centers were identified retrospectively. We compared times to stent dysfunction, causes of dysfunction, and procedural related complications between these two groups. RESULTS: Twenty patients were included in the study (7 EUS-BD and 13 transpapillary drainage). EUS-BD was performed via hepaticogastrostomy using a SEMS in three patients and via choledochoduodenostomy using a SEMS or a plastic stent in two patients each. Transpapillary drainage was performed using a SEMS in all patients. The stent patency rate in the EUS-BD group was higher than that in the transpapillary drainage group (100 vs. 71% at 1 month and 83 vs. 29% at 3 months, respectively). The rate of stent dysfunction in the EUS-BD group tended to be lower than that in the transpapillary group (14 vs. 54%; P = 0.157). Complication rates were similar between the groups (P = 1.000), with moderate bleeding in one patient in the EUS-BD group and mild pancreatitis in one patient in the transpapillary group. CONCLUSION: Endoscopic ultrasound-guided transmural biliary drainage is an alternative to transpapillary drainage in patients with an indwelling duodenal SEMS.

23 Article Prognostic nomogram for nonresectable pancreatic cancer treated with gemcitabine-based chemotherapy. 2014

Hamada, T / Nakai, Y / Yasunaga, H / Isayama, H / Matsui, H / Takahara, N / Sasaki, T / Takagi, K / Watanabe, T / Yagioka, H / Kogure, H / Arizumi, T / Yamamoto, N / Ito, Y / Hirano, K / Tsujino, T / Tada, M / Koike, K. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · Department of Health Economics and Epidemiology Research, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · Department of Gastroenterology, Kanto Central Hospital, 6-25-1 Kami-Yoga, Setagaya-ku, Tokyo 158-8531, Japan. · Department of Gastroenterology, JR Tokyo General Hospital, 2-1-3 Yoyogi, Shibuya-ku, Tokyo 151-8528, Japan. · Department of Gastroenterology, Mitsui Memorial Hospital, 1 Izumi-cho, Kanda, Chiyoda-ku, Tokyo 101-8643, Japan. · Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan. ·Br J Cancer · Pubmed #24642625.

ABSTRACT: BACKGROUND: A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported. METHODS: Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots. RESULTS: In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction. CONCLUSIONS: The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.

24 Article Metallic stent with high axial force as a risk factor for cholecystitis in distal malignant biliary obstruction. 2014

Nakai, Yousuke / Isayama, Hiroyuki / Kawakubo, Kazumichi / Kogure, Hirofumi / Hamada, Tsuyoshi / Togawa, Osamu / Ito, Yukiko / Matsubara, Saburo / Arizumi, Toshihiko / Yagioka, Hiroshi / Takahara, Naminatsu / Uchino, Rie / Mizuno, Suguru / Miyabayashi, Koji / Yamamoto, Keisuke / Sasaki, Takashi / Yamamoto, Natsuyo / Hirano, Kenji / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·J Gastroenterol Hepatol · Pubmed #24628054.

ABSTRACT: BACKGROUND AND AIM: Tumor involvement to the orifice of cystic duct (OCD) is a risk factor for cholecystitis after self-expandable metallic stent (SEMS) placement, but its prevention is still difficult. We conducted this multicenter analysis to clarify a type of SEMS or a method to place SEMS which would decrease the incidence of cholecystitis after SEMS placement. METHODS: The incidence of cholecystitis was studied in consecutive patients receiving SEMS for distal malignant biliary obstruction in five tertiary care centers. Multiple logistic regression analysis was performed to evaluate risk factors for cholecystitis. RESULTS: A total of 376 patients who received SEMS placement for distal malignant biliary obstruction were analyzed. Tumor involvement to OCD was diagnosed in 25.3%. Overall incidence of cholecystitis was 6.9%. Cholecystitis was observed in 8.0% of 300 patients with covered SEMS, 16.8% of 95 patients with tumor involvement to OCD, 10.8% of 234 patients with SEMS of high axial force (AF), and 12.0% of 158 patients with SEMS length ≤ 60 mm. In the multivariate analysis, tumor involvement to OCD (odds ratio [OR] 5.40, P < 0.001), SEMSs with high AF (OR 5.33, P = 0.002), and SEMS length ≤ 60 mm (OR 3.19, P = 0.010) are risk factors. Among patients with tumor involvement to OCD, the incidence of cholecystitis in SEMS with high and low AF was 25.0% and 5.0%, respectively. CONCLUSION: This study with an expanded cohort reconfirmed tumor involvement to OCD as a risk factor for cholecystitis after SEMS placement. SEMS with low AF might decrease cholecystitis.

25 Article Disease-specific mortality among patients with intraductal papillary mucinous neoplasm of the pancreas. 2014

Kawakubo, Kazumichi / Tada, Minoru / Isayama, Hiroyuki / Sasahira, Naoki / Nakai, Yousuke / Takahara, Naminatsu / Uchino, Rie / Hamada, Tsuyoshi / Miyabayashi, Koji / Yamamoto, Keisuke / Mizuno, Suguru / Mohri, Dai / Kogure, Hirofumi / Sasaki, Takashi / Yamamoto, Natsuyo / Hirano, Kenji / Ijichi, Hideaki / Tateishi, Keisuke / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: mtada-tky@umin.ac.jp. ·Clin Gastroenterol Hepatol · Pubmed #23892276.

ABSTRACT: BACKGROUND & AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with synchronous and metachronous pancreatic cancer. However, the risk factors for pancreatic cancer-specific mortality have not been determined. We evaluated disease-specific mortality among patients with IPMNs harboring high-risk stigmata. METHODS: We analyzed data from 243 patients diagnosed with IPMN, with indications for surgery according to the consensus criteria, at the University of Tokyo Hospital from 1995 to January 2011. By using optimal matching and propensity scores based on 16 characteristics, we matched patients who underwent surgery at diagnosis with those who did not undergo surgery. A competing risk analysis was used to assess the risk of pancreatic cancer-specific mortality. RESULTS: Fifty-nine patients underwent surgery after diagnosis and 184 did not. After adjustment with propensity scores, detection of a hypo-attenuating area by computed tomography, which indicates invasive carcinoma, was associated significantly with pancreatic cancer-specific mortality (adjusted hazard ratio, 16.75; 95% confidence interval, 2.72-103.3; P = .002). Cyst diameter, main pancreatic duct diameter, and the presence of a mural nodule were not associated significantly with pancreatic cancer-specific mortality. Surgical management was found to reduce pancreatic cancer-specific mortality, especially in patients with hypo-attenuating areas (P = .038). CONCLUSIONS: Detection of a hypo-attenuating area by computed tomography significantly increases the risk for pancreatic cancer-specific mortality among IPMN patients with consensus indications for surgery. Surgical resection significantly reduces this risk.

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