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Pancreatic Neoplasms: HELP
Articles by Hirofumi Kogure
Based on 58 articles published since 2010
(Why 58 articles?)
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Between 2010 and 2020, H. Kogure wrote the following 58 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 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.

2 Review Role of endoscopic ultrasonography in pancreatic cystic neoplasms: where do we stand and where will we go? 2014

Nakai, Yousuke / Isayama, Hiroyuki / Itoi, Takao / Yamamoto, Natsuyo / Kogure, Hirofumi / Sasaki, Takashi / Hirano, Kenji / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Dig Endosc · Pubmed #24219338.

ABSTRACT: We increasingly encounter pancreatic cystic neoplasms (PCN) in clinical practice and the differential diagnoses vary widely from benign to malignant. There is no 'one and only' diagnostic procedure for PCN. Multiple modalities including computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (EUS) are widely used, but EUS has the advantage of anatomical proximity to the pancreas and upper gastrointestinal tract. In addition, EUS-guided fine-needle aspiration (EUS-FNA) provides both cytological evaluation and cyst fluid analysis. Although the role of EUS-FNA for PCN is established, the sensitivity of cytology is low and cyst fluid analysis is only useful for differentiation between mucinous and non-mucinous cysts. Recently, novel through-the-needle imaging under EUS-FNA, such as confocal laserendomicroscopy, is expected to attribute to a better diagnostic yield. Moreover, feasibility of cyst ablation has been reported and the role of EUS has expanded from diagnosis to treatment. However, clinical impact of cyst ablation in terms of safety, efficacy and cost-effectiveness should be validated further. In summary, EUS and EUS-guided intervention does and will play a central role in the management of PCN from surveillance to treatment, but many clinical questions remain unanswered, which warrants well-designed prospective clinical trials.

3 Review Endoscopic retrograde cholangiopancreatography for distal malignant biliary stricture. 2012

Isayama, Hiroyuki / Nakai, Yousuke / Kawakubo, Kazumichi / Kogure, Hirofumi / Hamada, Tsuyoshi / Togawa, Osamu / Sasahira, Naoki / Hirano, Kenji / Tsujino, Takeshi / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. isayama-tky@umin.ac.jp ·Gastrointest Endosc Clin N Am · Pubmed #22748244.

ABSTRACT: Endoscopic biliary stent placement is widely accepted as palliation for malignant biliary obstruction or as a treatment of benign biliary stricture. Although various biliary stent designs have become available since self-expandable metallic stents were introduced, no single ideal stent has been developed. An ideal stent should be patent until death, or surgery, in patients with resectable malignant biliary obstruction. Fewer complications, maneuverability, cost-effectiveness, and removability are also important factors. Alternatively, should we develop a novel method for biliary drainage other than biliary stenting via endoscopic retrograde cholangiopancreatography? This article reviews the current status of biliary stenting for malignant biliary obstructions.

4 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.

5 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

6 Clinical Trial Preoperative biliary drainage using a fully covered self-expandable metallic stent for pancreatic head cancer: A prospective feasibility study. 2018

Togawa, Osamu / Isayama, Hiroyuki / Kawakami, Hiroshi / Nakai, Yousuke / Mohri, Dai / Hamada, Tsuyoshi / Kogure, Hirofumi / Kawakubo, Kazumichi / Sakamoto, Naoya / Koike, Kazuhiko / Kita, Hiroto. ·Department of Gastroenterology, Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo; Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo; Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan. · Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. ·Saudi J Gastroenterol · Pubmed #29652026.

ABSTRACT: Background/Aims: The role of endoscopic preoperative biliary drainage (PBD) for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. This study was performed to evaluate the feasibility and safety of PBD using a fully covered self-expandable metallic stent (FCSEMS). Patients and Methods: This multicenter prospective study involved 26 patients treated for pancreatic head cancer with distal bile duct obstruction from April 2011 to March 2013. An FCSEMS was endoscopically placed in 24 patients. Among these, 7 patients were diagnosed with unresectable cancer, and 17 underwent surgery at a median of 18 days after FCSEMS placement. The main outcome measure was preoperative and postoperative adverse events. Results: Two adverse events (cholecystitis and insufficient resolution of jaundice) occurred between FCSEMS placement and surgery (12%). Postoperative adverse events occurred in eight patients (47%). The cumulative incidence of stent-related adverse events 4 and 8 weeks after FCSEMS placement among the 24 patients who underwent this procedure were 19%. Conclusions: PBD using an FCSEMS is feasible in patients with resectable pancreatic head cancer. Placement of an FCSEMS can be an alternative PBD technique when surgery without delay is impossible. A larger randomized controlled trial is warranted.

7 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).

8 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.

9 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).

10 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).

11 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.

12 Clinical Trial A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. 2012

Nakai, Y / Isayama, H / Sasaki, T / Sasahira, N / Tsujino, T / Toda, N / Kogure, H / Matsubara, S / Ito, Y / Togawa, O / Arizumi, T / Hirano, K / Tada, M / Omata, M / Koike, K. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan. ·Br J Cancer · Pubmed #22555398.

ABSTRACT: BACKGROUND: This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer. METHODS: Patients were randomly assigned to 4-week treatment with gemcitabine alone (1000, mg m(-2) gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m(-2) gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m(-2) S-1 orally twice daily on days 1-15). The primary end point was progression-free survival (PFS). RESULTS: Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms. CONCLUSION: Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.

13 Clinical Trial Phase I trial of gemcitabine and candesartan combination therapy in normotensive patients with advanced pancreatic cancer: GECA1. 2012

Nakai, Yousuke / Isayama, Hiroyuki / Ijichi, Hideaki / Sasaki, Takashi / Kogure, Hirofumi / Yagioka, Hiroshi / Miyabayashi, Koji / Mizuno, Suguru / Yamamoto, Keisuke / Mouri, Dai / Kawakubo, Kazumichi / Yamamoto, Natsuyo / Hirano, Kenji / Sasahira, Naoki / Tateishi, Keisuke / Tada, Minoru / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Cancer Sci · Pubmed #22515232.

ABSTRACT: Our retrospective study showed inhibition of the renin-angiotensin system was associated with better outcomes in patients with advanced pancreatic cancer receiving gemcitabine. The primary objective of this phase I study was to determine the recommended dose of candesartan in combination with gemcitabine in normotensive patients with advanced pancreatic cancer. Candesartan was given orally at an escalating dose (4, 8, 16, and 32 mg) q.d. daily, and gemcitabine was given 1000 mg/m(2) 30 min i.v. on days 1, 8, and 15, repeated every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicities, grade 2 hypotension, abnormal creatinine or potassium, and grade 3 or 4 other non-hematological toxicities. A standard "3+3" phase I dose-escalation design was used. A total of 14 patients (candesartan 4 mg, three patients; 8 mg, three patients; 16 mg, six patients; 32 mg, two patients) were enrolled. One of six patients at 16 mg showed DLT of grade 4 neutropenia and two of two patients at 32 mg showed DLT of grade 2 hypotension. Response rate and disease control rate were 0% and 79%, respectively. Progression-free survival and overall survival were 7.6 and 22.9 months, respectively. Candesartan 16 mg is the recommended dose in combination with gemcitabine in the treatment of advanced pancreatic cancer. (UMIN CTR: UMIN000002152).

14 Clinical Trial Management of malignant gastric outlet obstruction with a modified triple-layer covered metal stent. 2012

Isayama, Hiroyuki / Sasaki, Takashi / Nakai, Yousuke / Togawa, Osamu / Kogure, Hirofumi / Sasahira, Naoki / Yashima, Yoko / Kawakubo, Kazumichi / Ito, Yukiko / Hirano, Kenji / Tsujino, Takeshi / Toda, Nobuo / Tada, Minoru / Omata, Masao / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ·Gastrointest Endosc · Pubmed #22284092.

ABSTRACT: BACKGROUND: A high incidence of migration with covered metal stents has been reported in malignant gastric outlet obstruction (GOO). A newly modified, partially covered, triple-layer nitinol stent was developed that has a longer uncovered portion (5-15 mm) to prevent stent migration. OBJECTIVE: To estimate the efficacy and safety of the modified covered, triple-layer metal stent. DESIGN: Multicenter, prospective cohort study. SETTING: Three tertiary referral centers. PATIENTS: Fifty consecutive patients (26 with pancreatic carcinoma, 14 with gastric carcinoma, 9 with cholangiocarcinoma, 1 with a metastatic node) who presented with symptomatic unresectable malignant GOO between April 2007 and March 2010. INTERVENTIONS: Endoscopic placement of the modified covered, triple-layer metal stent. MAIN OUTCOME MEASUREMENTS: The primary endpoint was to improve the GOO scoring system (GOOSS) score. Secondary endpoints were success rate, patency, and complications. RESULTS: The median GOOSS score improved significantly (P < .0001) after stenting (from 0 to 3). The technical and clinical success rates were 100% and 90%, respectively. Stent occlusion by tumor overgrowth or ingrowth at the uncovered portion developed in 5 patients (10%). Asymptomatic stent migration occurred in 3 patients (6%) receiving chemotherapy at 95, 230, and 553 days after stent placement, but these patients tolerated solid food 68, 260, and 142 days after stent migration, respectively. Other complications occurred in 1 patient with insufficient expansion, cholangitis, and pancreatitis. No procedure-related deaths occurred. LIMITATIONS: A single-arm study in tertiary-care centers. CONCLUSIONS: The modified covered, triple-layer metal stent was effective and safe for managing malignant GOO and can prevent tumor ingrowth and stent migration. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000004566.).

15 Clinical Trial Gemcitabine and oxaliplatin combination chemotherapy for patients with refractory pancreatic cancer. 2011

Isayama, Hiroyuki / Nakai, Yousuke / Yamamoto, Keisuke / Sasaki, Takashi / Mizuno, Suguru / Yagioka, Hiroshi / Yashima, Yoko / Kawakubo, Kazumichi / Kogure, Hirofumi / Arizumi, Toshihiko / Togawa, Osamu / Ito, Yukiko / Matsubara, Saburo / Yamamoto, Natsuyo / Sasahira, Naoki / Hirano, Kenji / Tsujino, Takeshi / Tada, Minoru / Omata, Masao / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. isayama-tky@umin.ac.jp ·Oncology · Pubmed #21677453.

ABSTRACT: OBJECTIVE: The aim of this study was to investigate the effect of gemcitabine and oxaliplatin combination chemotherapy on refractory pancreatic cancer. METHODS: Patients with advanced pancreatic cancer refractory to gemcitabine and S-1 were treated with gemcitabine 1,000 mg/m² over 30 min and oxaliplatin 85 mg/m² over 120 min on days 1 and 15. Treatment was repeated every 4 weeks and tumor response was assessed every two cycles by RECIST version 1.0. RESULTS: Twenty-two patients with pathologically confirmed pancreatic cancer were enrolled. The treatment was administered as a second-line chemotherapy in eighteen patients (82%) and as a third-line chemotherapy in four patients (18%). Tumor response did not occur in any of the cases. Thirteen patients demonstrated stable diseases, and the disease control rate was 59%. Median overall survival and time to progression were 6.8 months (95% CI, 2.8-11.5) and 2.6 months (95% CI, 1.5-3.8), respectively. Median overall survival from the first-line chemotherapy was 22.7 months (95% CI, 14.8-24.4). The major grade 3/4 adverse events included neutropenia (14%), anorexia (23%), and peripheral neuropathy (14%). CONCLUSIONS: Gemcitabine and oxaliplatin combination chemotherapy was tolerable but had limited activity in patients with advanced pancreatic cancer in a refractory setting.

16 Clinical Trial Impact of S-1 in patients with gemcitabine-refractory pancreatic cancer in Japan. 2010

Nakai, Yousuke / Isayama, Hiroyuki / Sasaki, Takashi / Sasahira, Naoki / Kogure, Hirofumi / Hirano, Kenji / Tsujino, Takeshi / Ijichi, Hideaki / Tateishi, Keisuke / Tada, Minoru / Omata, Masao / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan. ·Jpn J Clin Oncol · Pubmed #20462979.

ABSTRACT: OBJECTIVE: We investigated the impact of S-1 on the prognosis of patients with gemcitabine-refractory pancreatic cancer. METHODS: A total of 108 patients with gemcitabine-refractory pancreatic cancer were divided by the time of S-1 introduction in our institution: 47 patients who experienced progressive disease before February 2005 (pre-S-1 group) and 61 patients showed progressive disease after February 2005 (post-S-1 group). Introduction rates of second-line chemotherapy and survival were compared. Prognostic factors for residual survival were analyzed using the Cox proportional hazards model. RESULTS: Introduction rates of second-line chemotherapy were 12.8% in the pre-S-1 group and 45.9% in the post-S-1 group. Second-line chemotherapy was administered to 34 patients: 29 using S-1, 4 using 5-fluorouracil-based chemoradiation and 1 using 5-fluorouracil. The objective response rate, progression-free survival and overall survival for second-line chemotherapy with S-1 were 17.2%, 2.5 and 7.7 months, respectively. By the introduction of S-1 in our institution, residual survival was prolonged from 3.1 months in the pre-S-1 group to 6.7 months in the post-S-1 group (P < 0.001). Overall survival from the initiation of gemcitabine was 8.8 months in the pre-S-1 group and 11.3 months in the post-S-1 group (P = 0.013). Multivariate analysis identified the post-S-1 group (hazard ratio, 0.43; P = 0.001), gender, performance status, liver metastasis, and lactate dehydrogenase and C-reactive protein levels at progressive disease for gemcitabine to be prognostic factors for residual survival. CONCLUSIONS: The introduction of S-1 might improve the prognosis of patients with gemcitabine-refractory pancreatic cancer.

17 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.

18 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.

19 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.

20 Article Antireflux covered metal stent for nonresectable distal malignant biliary obstruction: Multicenter randomized controlled trial. 2019

Hamada, Tsuyoshi / Isayama, Hiroyuki / Nakai, Yousuke / Iwashita, Takuji / Ito, Yukiko / Mukai, Tsuyoshi / Yagioka, Hiroshi / Saito, Tomotaka / Togawa, Osamu / Ryozawa, Shomei / Hirano, Kenji / Mizuno, Suguru / Yamamoto, Natsuyo / Kogure, Hirofumi / Yasuda, Ichiro / Koike, Kazuhiko. ·Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo. · Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA. · Department of Gastroenterology, Graduate School of Medicine, Juntendo University. · First Department of Internal Medicine, Gifu University Hospital. · Department of Gastroenterology, Japanese Red Cross Medical Center. · Department of Gastroenterology, Gifu Municipal Hospital, Gifu. · Department of Gastroenterology, Tokyo Metropolitan Police Hospital. · Department of Gastroenterology, JR Tokyo General Hospital. · Department of Gastroenterology, Kanto Central Hospital. · Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama. · Department of Gastroenterology, JCHO Tokyo Takanawa Hospital. · Department of Gastroenterology, Toshiba General Hospital, Tokyo. · Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, Kanagawa, Japan. ·Dig Endosc · Pubmed #30803046.

ABSTRACT: BACKGROUND AND AIM: An antireflux metal stent (ARMS) for nonresectable distal malignant biliary obstruction (MBO) may prevent recurrent biliary obstruction (RBO) as a result of duodenobiliary reflux and prolong time to RBO (TRBO). Superiority of ARMS over conventional covered self-expandable metal stents (SEMS) has not been fully examined. METHODS: We conducted a multicenter randomized controlled trial to examine whether TRBO of an ARMS with a funnel-shaped valve was longer than that of a covered SEMS in SEMS-naïve patients. We enrolled 104 patients (52 patients per arm) at 11 hospitals in Japan. Secondary outcomes included causes of RBO, adverse events, and patient survival. RESULTS: TRBO did not differ significantly between the ARMS and covered SEMS groups (median, 251 vs 351 days, respectively; P = 0.11). RBO as a result of biliary sludge or food impaction was observed in 13% and 9.8% of patients who received an ARMS and covered SEMS, respectively (P = 0.83). ARMS was associated with a higher rate of stent migration compared with the covered SEMS (31% vs 12%, P = 0.038). Overall rates of adverse events were 20% and 18% in the ARMS and covered SEMS groups, respectively (P = 0.97). No significant between-group difference in patient survival was observed (P = 0.26). CONCLUSIONS: The current ARMS was not associated with longer TRBO compared with the covered SEMS. Modifications including addition of an anti-migration system are required to use the current ARMS as first-line palliative treatment of distal MBO (UMIN-CTR clinical trial registration number: UMIN000014784).

21 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.

22 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.

23 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.

24 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.

25 Article Diagnostic and Therapeutic Endoscopic Retrograde Cholangiography Using a Short-Type Double-Balloon Endoscope in Patients With Altered Gastrointestinal Anatomy: A Multicenter Prospective Study in Japan. 2016

Shimatani, Masaaki / Hatanaka, Hisashi / Kogure, Hirofumi / Tsutsumi, Koichiro / Kawashima, Hiroki / Hanada, Keiji / Matsuda, Tomoki / Fujita, Tomoki / Takaoka, Makoto / Yano, Tomonori / Yamada, Atsuo / Kato, Hironari / Okazaki, Kazuichi / Yamamoto, Hironori / Ishikawa, Hideki / Sugano, Kentaro / Anonymous16340882. ·The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan. · Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. · Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. · Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan. · Digestive Endoscopy Center, Sendai Kousei Hospital, Sendai, Japan. · Center for Gastroenterology, Otaru Ekisaikai Hospital, Hokkaido, Japan. · Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan. ·Am J Gastroenterol · Pubmed #27670601.

ABSTRACT: OBJECTIVES: To evaluate the utility and safety of a short-type double-balloon endoscope (DBE) in the treatment of biliary disease in patients with surgically altered gastrointestinal (GI) anatomy. METHODS: This study was conducted as a multicenter, single-arm, prospective trial at five tertiary academic care centers and three community-based hospitals in Japan. Consecutive patients with biliary disease with altered GI anatomy were prospectively included in this study. RESULTS: A total of 311 patients underwent double-balloon endoscopic retrograde cholangiography (ERC). The success rate of reaching the target site, the primary end point, was 97.7% (95% confidence interval (CI): 95.4-99.1). The success rate of biliary cannulation and contrast injection of the targeted duct, the secondary end point, was 96.4% (95% CI: 93.6-98.2), and the therapeutic success rate was 97.9% (95% CI: 95.4-99.2). Adverse events occurred in 33 patients (10.6%, 95% CI: 7.1-14.0) and were managed conservatively in all patients with the exception of 1 in whom a perforation developed, requiring emergency surgery. CONCLUSIONS: ERC using a short-type DBE resulted in an excellent therapeutic success rate and a low rate of adverse events. This treatment can be a first-line treatment for biliary disease in patients with surgically altered GI anatomy.

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