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Pancreatic Neoplasms: HELP
Articles by Tooru Shimosegawa
Based on 64 articles published since 2009
(Why 64 articles?)
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Between 2009 and 2019, Tooru Shimosegawa wrote the following 64 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Clinical Practice Guidelines for Pancreatic Cancer 2016 From the Japan Pancreas Society: A Synopsis. 2017

Yamaguchi, Koji / Okusaka, Takuji / Shimizu, Kyoko / Furuse, Junji / Ito, Yoshinori / Hanada, Keiji / Shimosegawa, Tooru / Okazaki, Kazuichi / Anonymous7740903. ·From the *Clinic of Fukuoka Government Building, Hamanomachi Hospital, Fukuoka; †Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital; ‡Department of Gastroenterology, Tokyo Women's Medical University; §Department of Medical Oncology, Faculty of Medicine, Kyorin University; ∥Department of Radiation Oncology, National Cancer Center Hospital, Tokyo; ¶Department of Gastroenterology, JA Onomichi General Hospital, Onomichi; #Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai; and **Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan. ·Pancreas · Pubmed #28426492.

ABSTRACT: OBJECTIVES: Clinical Practice Guidelines for Pancreatic Cancer based on Evidence-Based Medicine 2006 were first published by the Japan Pancreas Society, and they were revised to Clinical Practice Guidelines for Pancreatic Cancer 2009 in July 2009 and were further revised to Clinical Practice Guidelines for Pancreatic Cancer 2013 in October 2013. These guidelines were established according to evidence-based medicine. In October 2016, the Clinical Practice Guidelines for Pancreatic Cancer were newly revised in Japanese. METHODS: In the revised version, we introduced the concepts of GRADE - grading recommendations assessment, development, and evaluation approach for better understanding of the current guidelines. RESULTS: The guidelines show algorithms for the diagnosis, treatment, and chemotherapy of pancreatic cancer and address 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and palliative medicine. They include 51 clinical questions and 76 statements. There are statements corresponding to clinical questions, evidence levels, recommended strengths, and agreement rates. CONCLUSIONS: These guidelines represent the most standard clinical and practical management at this time in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2016 in Japanese, which aims to disseminate the Japanese guidelines worldwide for the introduction of Japanese clinical management of these diseases.

2 Guideline EBM-based Clinical Guidelines for Pancreatic Cancer (2013) issued by the Japan Pancreas Society: a synopsis. 2014

Yamaguchi, Koji / Okusaka, Takuji / Shimizu, Kyoko / Furuse, Junji / Ito, Yoshinori / Hanada, Keiji / Shimosegawa, Tooru / Anonymous6910805. ·Department of Advanced Treatment of Pancreatic Diseases, School of Medicine, University of Occupational and Environmental Health, Kitakyushu yamaguch@med.uoeh-u.ac.jp. · Hepatobiliary and Pancreatic Oncology Division, National Cancer Center, Tokyo. · Department of Gastroenterology, Tokyo Women's Medical University, Tokyo. · Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, Tokyo. · Department of Radiation Oncology, National Cancer Center, Tokyo. · Department of Gastroenterology, JA Onomichi General Hospital, Onomichi. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. ·Jpn J Clin Oncol · Pubmed #25205672.

ABSTRACT: Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.

3 Editorial [Pancreatic tumor: progress in diagnosis and treatment. Editorial: trend of clinical management of pancreatic tumors]. 2012

Shimosegawa, Tooru. · ·Nihon Naika Gakkai Zasshi · Pubmed #22413454.

ABSTRACT: -- No abstract --

4 Editorial Inflammation and carcinogenesis in the pancreas and biliary tract: mechanisms and practice. 2009

Shimosegawa, Tooru / Gorelick, Fred S. · ·Clin Gastroenterol Hepatol · Pubmed #19896089.

ABSTRACT: -- No abstract --

5 Review [Chronic pancreatitis is a risk factor of pancreatic cancer]. 2015

Masamune, Atsushi / Hamada, Shin / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #26250125.

ABSTRACT: -- No abstract --

6 Review Pancreatic stellate cells: A dynamic player of the intercellular communication in pancreatic cancer. 2015

Masamune, Atsushi / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: amasamune@med.tohoku.ac.jp. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. ·Clin Res Hepatol Gastroenterol · Pubmed #26189983.

ABSTRACT: There is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis within the pancreatic cancer tissue. Not only do they produce extracellular matrix components, PSCs dynamically interact with other cell types to constitute the cancer-conditioned microenvironment. There exist bidirectional interactions between PSCs and pancreatic cancer cells. Pancreatic cancer cells promote the proliferation, migration, extracellular matrix production and degradation, and angiogenetic responses in PSCs. In turn, PSCs promote the proliferation and migration, and inhibit the apoptosis of pancreatic cancer cells. PSCs also induce epithelial-mesenchymal transition and stem cell like phenotypes in pancreatic cancer cells, resulting in resistance to conventional therapies, distant metastasis, and recurrence. PSCs interact with endothelial cells, neural cells and β-cells, leading to angiogenesis, neurogenesis and β-cell dysfunction and apoptosis. PSCs cause impaired immune responses and help pancreatic cancer cells escape from host immune-surveillance. PSCs induce the differentiation of myeloid-derived suppressor cells, induce the apoptosis of T cells, inhibit the infiltration of T cells, and induce the activation of mast cells. Overall, these interactions appear to promote the progression of pancreatic cancer, and anti-stroma therapies targeting PSCs are under intense investigation. Further elucidation of these interactions could lead to the identification of novel therapeutic targets in pancreatic cancer.

7 Review Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma. 2015

Satoh, Kennichi / Hamada, Shin / Shimosegawa, Tooru. ·Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, Japan, ksatoh-gi@umin.ac.jp. ·J Gastroenterol · Pubmed #25216997.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an intractable disease as a result of its rapid dissemination and resistance to conventional chemotherapy and radiotherapy. Surgical resection is the only curative therapy, but most of the tumors are unresectable at the time of diagnosis. The molecular mechanisms underlying the biological aggressiveness of this tumor type remain to be clarified. Epithelial to mesenchymal transition (EMT) is a developmental process that leads the phenotype shift from an epithelial morphology to a motile, fibroblast-like morphology. Recent studies showed that EMT is involved in the invasion and metastasis of many types of carcinomas including PDAC. In addition, PDAC cells with the EMT phenotype also exhibit chemoresistance and the cancer stem cell property. Various factors such as cytokines, growth factors, or transcriptional factors were found to promote the EMT program in PDAC cells. In this review, we summarize the current knowledge about the EMT in PDAC cells, focusing on the involvement of this process and its regulatory molecules including microRNA during the development of PDAC cells.

8 Review Inflammation and pancreatic cancer: disease promoter and new therapeutic target. 2014

Hamada, Shin / Masamune, Atsushi / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi Aobaku, Sendai, Miyagi, 980-8574, Japan, hamadas@med.tohoku.ac.jp. ·J Gastroenterol · Pubmed #24292163.

ABSTRACT: Chronic inflammation has a certain impact on the carcinogenesis of the digestive organs. The characteristic tissue structure of pancreatic cancer, desmoplasia, results from inflammatory processes induced by cancer cells and stromal cells. Concerning the progression of pancreatic cancer, recent research has clarified the pivotal role of tumor-stromal interaction, which promotes the development of an invasive phenotype of cancer and provides survival advantages against chemotherapeutic agents or immune surveillance. Tumor stromal cells such as pancreatic stellate cells and immune cells establish a microenvironment that protects cancer cells through complex interactions. The microenvironment of pancreatic cancer acts as a niche for pancreatic cancer stem cells from which therapy-resistance and disease recurrence develop. Inhibition of the stromal functions or restoration of the immune reaction against cancer cells has therapeutic benefits that enhance the efficacy of conventional therapies. Some of the recent advances in this field are now under evaluation in clinical settings, but many problems must be overcome to establish a radical therapy for pancreatic cancer. This review summarizes current knowledge about the tumor-promoting stromal functions, immune system modulation and therapeutic strategies targeting tumor-stromal interactions in pancreatic cancer.

9 Review Clinical importance of Familial Pancreatic Cancer Registry in Japan: a report from kick-off meeting at International Symposium on Pancreas Cancer 2012. 2013

Wada, Keita / Takaori, Kyoichi / Traverso, L William / Hruban, Ralph H / Furukawa, Toru / Brentnall, Teresa A / Hatori, Takashi / Sano, Keiji / Takada, Tadahiro / Majima, Yoshiyuki / Shimosegawa, Tooru. ·Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga Itabashi-ku, Tokyo, 173-8605, Japan. wada@med.teikyo-u.ac.jp. ·J Hepatobiliary Pancreat Sci · Pubmed #23604538.

ABSTRACT: Pancreatic cancer is still a highly lethal disease with a 5-year survival rate of approximately 5 %. Early detection offers one of the best hopes for improving survival. Previous cohort studies and case-control studies showed that 4-10 % of pancreatic cancers have a hereditary basis, and individuals with a family history have an increased risk of developing pancreatic and extra-pancreatic malignancies. Since individuals with a family history of pancreatic cancer and those with a known genetic syndrome that predisposes to pancreatic cancer will be the first to benefit from early detection tests as they become available, familial pancreatic cancer (FPC) registries have been established in the US and Europe, but not yet in Japan. Such registries form the basis for epidemiological studies, clinical trials, and basic research on familial pancreatic cancer. There is a need for FPC registries in Japan as cancer risk varies among different populations and discoveries made in Western populations may not translate to the Japanese population. These registries in Japan will align with ongoing international efforts and add to a better understanding of the natural history, risk factors, screening strategies, and responsible genes, for improving survival of this dismal disease.

10 Review [Pancreatic tumor: progress in diagnosis and treatment. Topics: I. Pancreatic carcinoma: 2. Pathogenesis and pathobiology in pancreatic cancer.--The molecular mechanisms of carcinogenesis, and invasion and metastasis in pancreatic cancer]. 2012

Satoh, Kennichi / Shimosegawa, Tooru. ·Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Japan. ·Nihon Naika Gakkai Zasshi · Pubmed #22413456.

ABSTRACT: -- No abstract --

11 Review Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. 2009

Masamune, Atsushi / Watanabe, Takashi / Kikuta, Kazuhiro / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. amasamune@m.tains.tohoku.ac.jp ·Clin Gastroenterol Hepatol · Pubmed #19896099.

ABSTRACT: Over a decade, there is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis. In response to pancreatic injury or inflammation, quiescent PSCs are transformed (activated) to myofibroblast-like cells, which express alpha-smooth muscle actin. Activated PSCs proliferate, migrate, produce extracellular matrix components, such as type I collagen, and express cytokines and chemokines. Recent studies have suggested novel roles of PSCs in local immune functions and angiogenesis in the pancreas. If the pancreatic inflammation and injury are sustained or repeated, PSC activation is perpetuated, leading to the development of pancreatic fibrosis. In this context, pancreatic fibrosis can be defined as pathologic changes of extracellular matrix composition in both quantity and quality, resulting from perpetuated activation of PSCs. Because PSCs are very similar to hepatic stellate cells, PSC research should develop in directions more relevant to the pathophysiology of the pancreas, for example, issues related to trypsin, non-oxidative alcohol metabolites, and pancreatic cancer. Indeed, in addition to their roles in chronic pancreatitis, it has been increasingly recognized that PSCs contribute to the progression of pancreatic cancer. Very recently, contribution of bone marrow-derived cells to PSCs was reported. Further elucidation of the roles of PSCs in pancreatic fibrosis should promote development of rational approaches for the treatment of chronic pancreatitis and pancreatic cancer.

12 Review [Pancreatitis-associated genes and development of pancreatic cancer]. 2009

Masamune, Atsushi / Kume, Kiyoshi / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan. amasamune@m.tains.tohoku.ac.jp ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #19654461.

ABSTRACT: -- No abstract --

13 Review Signal transduction in pancreatic stellate cells. 2009

Masamune, Atsushi / Shimosegawa, Tooru. ·Division of Gastroenterology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. amasamune@int3.med.tohoku.ac.jp ·J Gastroenterol · Pubmed #19271115.

ABSTRACT: Pancreatic fibrosis is a characteristic feature of chronic pancreatitis and of desmoplastic reaction associated with pancreatic cancer. For over a decade, there has been accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis in these pathological settings. In response to pancreatic injury or inflammation, quiescent PSCs undergo morphological and functional changes to become myofibroblast-like cells, which express alpha-smooth muscle actin (alpha-SMA). Activated PSCs actively proliferate, migrate, produce extracellular matrix (ECM) components, such as type I collagen, and express cytokines and chemokines. In addition, PSCs might play roles in local immune functions and angiogenesis in the pancreas. Following the initiation of activation, if the inflammation and injury are sustained or repeated, PSCs activation is perpetuated, leading to the development of pancreatic fibrosis. From this point of view, pancreatic fibrosis can be defined as pathological changes of ECM composition in the pancreas both in quantity and quality, resulting from perpetuated activation of PSCs. Because the activation and cell functions in PSCs are regulated by the dynamic but coordinated activation of intracellular signaling pathways, identification of signaling molecules that play a crucial role in PSCs activation is important for the development of anti-fibrosis therapy. Recent studies have identified key mediators of stimulatory and inhibitory signals. Signaling molecules, such as peroxisome proliferator-activated receptor-gamma (PPAR-gamma), Rho/Rho kinase, nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases, phosphatidylinositol 3 kinase (PI3K), Sma- and Mad-related proteins, and reactive oxygen species (ROS) might be candidates for the development of anti-fibrosis therapy targeting PSCs.

14 Article Pancreatic Acinar Cell Carcinoma with Multiple Liver Metastases Effectively Treated by S-1 Chemotherapy. 2018

Yoshida, Naoki / Kanno, Atsushi / Masamune, Atsushi / Nabeshima, Tatsuhide / Hongo, Seiji / Miura, Shin / Takikawa, Tetsuya / Hamada, Shin / Kikuta, Kazuhiro / Kume, Kiyoshi / Ueno, Masamichi / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan. · Division of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Japan. ·Intern Med · Pubmed #30101903.

ABSTRACT: A 79-year-old woman was referred for pancreatic tail cancer with multiple liver metastases. The pancreatic tail tumor was diagnosed as acinar cell carcinoma (ACC) histologically by endoscopic ultrasound-guided fine-needle aspiration. Because of multiple liver metastases, S-1 chemotherapy was administered, resulting in a partial response to chemotherapy one year later. After approximately three years, liver atrophy and esophageal varices developed. We suspected S-1 as the cause of the liver cirrhosis. S-1 cessation minimized ascites and improved the esophageal varices. Although S-1 can potentially treat ACC, we should be watchful for liver cirrhosis caused by its long-term administration.

15 Article Pyruvate Kinase Isozyme M2 Plays a Critical Role in the Interactions Between Pancreatic Stellate Cells and Cancer Cells. 2018

Masamune, Atsushi / Hamada, Shin / Yoshida, Naoki / Nabeshima, Tatsuhide / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. amasamune@med.tohoku.ac.jp. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. ·Dig Dis Sci · Pubmed #29619774.

ABSTRACT: BACKGROUND: The interaction between pancreatic cancer cells and pancreatic stellate cells plays a pivotal role in the progression of pancreatic cancer. Pyruvate kinase isozyme M2 is a key enzyme in glycolysis. Previous studies have shown that pyruvate kinase isozyme M2 is overexpressed in pancreatic cancer and that it regulates the aggressive behaviors of pancreatic cancer cells. AIMS: To clarify the role of pyruvate kinase isozyme M2 in the interactions between pancreatic cancer cells and pancreatic stellate cells. METHODS: Pyruvate kinase isozyme M2-knockdown pancreatic cancer cells (Panc-1 and SUIT-2 cells) and pancreatic stellate cells were generated by the introduction of small interfering RNA-expressing vector against pyruvate kinase isozyme M2. Cell proliferation, migration, and epithelial-mesenchymal transition were examined in vitro. The impact of pyruvate kinase isozyme M2 knockdown on the growth of subcutaneous tumors was examined in nude mice in vivo. RESULTS: Pyruvate kinase isozyme M2-kockdown pancreatic cancer cells and pancreatic stellate cells showed decreased proliferation and migration compared to their respective control cells. Pancreatic stellate cell-induced proliferation, migration, and epithelial-mesenchymal transition were inhibited when pyruvate kinase isozyme M2 expression was knocked down in pancreatic cancer cells. In vivo, co-injection of pancreatic stellate cells increased the size of the tumor developed by the control SUIT-2 cells, but the effects were less evident when pyruvate kinase isozyme M2 was knocked down in SUIT-2 cells or pancreatic stellate cells. CONCLUSIONS: Our results suggested a critical role of pyruvate kinase isozyme M2 in the interaction between pancreatic cancer cells and pancreatic stellate cells.

16 Article [Conversion Surgery for Pancreatic Head Cancer with Peritoneal Dissemination Following Chemotherapy for Two Years - A Case Report]. 2018

Hatsuzawa, Yuuri / Mizuma, Masamichi / Motoi, Fuyuhiko / Hata, Tatsuo / Iseki, Masahiro / Takadate, Tatsuyuki / Ohtsuka, Hideo / Sakata, Naoaki / Morikawa, Takanori / Nakagawa, Kei / Hayashi, Hiroki / Naitoh, Takeshi / Kanno, Atsushi / Shimosegawa, Tooru / Unno, Michiaki. ·Dept. of Surgery, Tohoku University Graduate School of Medicine. ·Gan To Kagaku Ryoho · Pubmed #29483443.

ABSTRACT: Here we report a case of pancreatic cancer(PC)with peritoneal dissemination, underwent conversion surgery following chemotherapy for 2 years. A5 5-year-old woman was referred to our hospital for treatment of PC. Abdominal CT scan revealed 3.0 cm of a pancreatic head tumor with abutment of the portal vein and the hepatic artery, classified as borderline resectable. Staging laparoscopy(SL)showed positive peritoneal cytology(CY). Gemcitabine(Gem)plus S-1 therapy(GS) was performed. Ten months after initial GS, SL revealed the disseminated nodule and positive CY. The regimen was changed to Gem plus nab-paclitaxel therapy(Gem plus nab-PTX). Since right ovarian tumor was detected by CT scan 6 months after initial Gem plus nab-PTX, laparoscopic oophorectomy was performed. Histological findings showed positive CY and ovarian metastasis of PC. Afterward, Gem plus nab-PTX has been continued for 8 months. Since SL after 2 years from initial chemotherapy showed negative CY and no metastatic lesion, pancreaticoduodenectomy with portal vein resection was performed as conversion surgery. According to General Rules for the Study of Pancreatic Cancer the 7th edition by Japan Pancreas Society, histological findings showed ypT3, ypN0, R0, and Grade 1b of histological effect. The patient is alive without recurrence 6 months after the resection.

17 Article Multicenter study of early pancreatic cancer in Japan. 2018

Kanno, Atsushi / Masamune, Atsushi / Hanada, Keiji / Maguchi, Hiroyuki / Shimizu, Yasuhiro / Ueki, Toshiharu / Hasebe, Osamu / Ohtsuka, Takao / Nakamura, Masafumi / Takenaka, Mamoru / Kitano, Masayuki / Kikuyama, Masataka / Gabata, Toshifumi / Yoshida, Koji / Sasaki, Tamito / Serikawa, Masahiro / Furukawa, Toru / Yanagisawa, Akio / Shimosegawa, Tooru / Anonymous880928. ·Division of Gastroenterology, Tohoku University, Graduate School of Medicine, Japan. Electronic address: atsushih@med.tohoku.ac.jp. · Division of Gastroenterology, Tohoku University, Graduate School of Medicine, Japan. · Department of Gastroenterology, JA Onomichi General Hospital, Japan. · Center for Gastroenterology, Teine-Keijinkai Hospital, Japan. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Japan. · Department of Gastroenterology, Fukuoka University Chikushi Hospital, Japan. · Department of Gastroenterology, Nagano Municipal Hospital, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Japan. · Department of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Japan. · Second Department of Internal Medicine, Wakayama Medical University, School of Medicine, Japan. · Division of Gastroenterology, Shizuoka General Hospital, Japan. · Department of Radiology, Kanazawa University Hospital, Japan. · Department of Interventional Bilio-Pancreatology, Kawasaki Medical School, Japan. · Department of Gastroenterology, Hiroshima Prefectural Hospital, Japan. · Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Japan. · Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Japan; Department of Histopathology, Tohoku University, Graduate School of Medicine, Japan. · Department of Pathology, Kyoto Prefectural University of Medicine, Japan. ·Pancreatology · Pubmed #29170051.

ABSTRACT: BACKGROUND/OBJECTIVES: The diagnosis of early-stage pancreatic ductal adenocarcinoma (PDAC) is still challenging. We conducted a multicenter study to clarify the clinical features of early-stage PDAC in Japan. METHODS: We collected patients with stage 0 and stage I PDAC according to the sixth edition of the Japanese Classification of Pancreatic Carcinoma. We retrospectively analyzed the clinical profiles including opportunities for medical examination, imaging modalities and findings, methods of cytological diagnosis, and prognosis according to the stages at diagnosis. RESULTS: Two hundred cases with Stage 0 and stage I PDAC were reported from 14 institutions, which accounted for approximately 0.7% and 3% of all PDAC cases, respectively. Overall, 20% of the early-stage PDAC cases were symptomatic. Indirect imaging findings such as dilatation of the main pancreatic duct were useful to detect early-stage PDAC. In particular, local fatty changes may be specific to early-stage PDAC. For preoperative pathologic diagnosis, cytology during endoscopic retrograde cholangiopancreatography was more commonly applied than endoscopic ultrasound fine-needle aspiration. Although the overall prognosis was favorable, new PDAC lesions developed in the remnant pancreas in 11.5% cases. CONCLUSIONS: This multicenter study revealed several key points concerning the diagnosis and management of early-stage PDAC, including screening of asymptomatic cases, importance of indirect imaging findings, application of cytology during endoscopic retrograde cholangiopancreatography, and the risk of carcinogenesis in the remnant pancreas.

18 Article Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells. 2018

Masamune, Atsushi / Yoshida, Naoki / Hamada, Shin / Takikawa, Tetsuya / Nabeshima, Tatsuhide / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: amasamune@med.tohoku.ac.jp. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. ·Biochem Biophys Res Commun · Pubmed #29111329.

ABSTRACT: Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment.

19 Article Nationwide survey of hereditary pancreatitis in Japan. 2018

Masamune, Atsushi / Kikuta, Kazuhiro / Hamada, Shin / Nakano, Eriko / Kume, Kiyoshi / Inui, Ayano / Shimizu, Toshiaki / Takeyama, Yoshifumi / Nio, Masaki / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. amasamune@med.tohoku.ac.jp. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. · Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Yokohama, Japan. · Department of Pediatrics, Juntendo University, Tokyo, Japan. · Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan. · Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. ·J Gastroenterol · Pubmed #28861620.

ABSTRACT: BACKGROUND: Hereditary pancreatitis (HP) is a rare cause of chronic pancreatitis. We here report a nationwide survey to clarify the epidemiological, genetic, and clinical features of HP in Japan. METHODS: Target subjects were patients with HP and their family members who had visited selected hospitals between 2005 and 2014. This study consisted of two-stage surveys; patients with HP were identified by the first questionnaire and their clinical features were assessed by the second questionnaire. RESULTS: Two hundred seventy-one patients (153 males and 118 females) in 100 families diagnosed based on the Japanese criteria or 231 patients (131 males and 100 females) patients in 80 families based on the EUROPAC criteria were reported. Of the families undertaking genetic tests, 41% had the PRSS1 mutations (p.R122H 33%, p.N29I 8%) and 36% had the SPINK1 mutations (p.N34S 22%, c.194+2T>C 14%, p.P45S 1%). The mean age at symptom onset was 17.8 years. The cumulative rates of pancreatic exocrine insufficiency and diabetes mellitus were 16.1 and 5.5% at 20 years old, and 45.3 and 28.2% at 40 years, respectively. Forty-four percent of the patients underwent endoscopic treatment and/or surgery. The cumulative rate of pancreatic cancer diagnosis was 2.8% at 40 years old, 10.8% at 60 years, and 22.8% at 70 years. CONCLUSIONS: HP was characterized by early disease onset, frequent development of pancreatic exocrine insufficiency and diabetes mellitus, requirement of endoscopic treatment and/or surgery, and increased risk of pancreatic cancer. PRSS1 and SPINK1 mutations serve as genetic background for HP in Japan.

20 Article [A Case of Successful Adjuvant Surgery for the Pancreas Head Cancer with Peritoneal Metastasis]. 2017

Kyakumoto, Yukie / Takadate, Tatsuyuki / Mizuma, Masamichi / Hata, Tatsuo / Iseki, Masahiro / Ohtsuka, Hideo / Sakata, Naoaki / Nakagawa, Kei / Morikawa, Takanori / Hayashi, Hiroki / Motoi, Fuyuhiko / Naitoh, Takeshi / Kanno, Atsushi / Shimosegawa, Tooru / Unno, Michiaki. ·Dept. of Surgery, Tohoku University Graduate School of Medicine. ·Gan To Kagaku Ryoho · Pubmed #29394807.

ABSTRACT: We report a case of the pancreas head cancer with peritoneal metastasis, which was resected curatively after chemotherapy. A6 6-year-old male was referred to our hospital for the treatment of biliary stenosis. The serum CA19-9 level was elevated and abdominal CT scan showed stenosis of distal bile duct. By laparotomy, we noticed mass in the head of the pancreas with 8mm of the seeding nodule in a diameter at jejunal mesentery which was diagnosed as adenocarcinoma by intraoperative frozen sections. Therefore, the patient was diagnosed as pancreas head cancer with peritoneal metastasis. After hepaticojejunostomy, we started chemotherapy planning adjuvant surgery if the clinical response was observed. Systemic chemotherapy with gemcitabine and nab-paclitaxel was administrated on days 1, 8 and 15 every 4 weeks. After 5 courses, therapeutic effect was stable disease(SD)in response evaluation criteria in solid tumor(RECIST). All of tumor markers were normalized. Subtotal stomach-preserving pancreatoduodenectomy(SSPPD)was performed 6 months after the initial surgery. Histopathologically, most cancer cells showed degeneration and eliminated in the head of the pancreas. R0 resection was achieved with diagnosis of ypT3, ypN1, pM1(PER), Stage IV . Histological therapeutic effect was Grade III according to the Evans classification. The patient is alive, with no sign of recurrence 8 months after surgery. Adjuvant surgery was suggested to be one of the therapeutic options for pancreatic cancer with peritoneal metastasis.

21 Article Nrf2 promotes mutant K-ras/p53-driven pancreatic carcinogenesis. 2017

Hamada, Shin / Taguchi, Keiko / Masamune, Atsushi / Yamamoto, Masayuki / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. · Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. ·Carcinogenesis · Pubmed #29240881.

ABSTRACT: The Keap1-Nrf2 system contributes to the maintenance of homeostasis by regulating oxidative stress responses in normal tissues and organs, and is exploited in various cancers for proliferation, survival and acquisition of therapy resistance. Pancreatic cancer remains one of the intractable cancers, despite the improved clinical outcomes of other types of cancer, due to its invasive and refractory nature to therapeutic intervention. The current study aimed to clarify the contribution of Nrf2 to pancreatic carcinogenesis using a pancreas-specific mutant K-ras and p53 (KPC) mouse model. Deletion of Nrf2 in KPC mice (KPCN) decreased the formation of precancerous lesions as well as the development of invasive pancreatic cancer. The pancreatic tumor-derived cancer cell lines from KPCN mouse showed decreased expression of glutathione S-transferases (GST), UDP glucuronosyltransferases (UGT) and ABC transporters. Along with these biochemical changes, cell lines from KPCN mice revealed increased sensitivity to oxidative stress and chemotherapeutic agent. The current study revealed that Nrf2 contributes to pancreatic carcinogenesis in a way distinct from the chemoresistance of lung and esophagus, and that Nrf2 could be a novel therapeutic target of pancreatic cancer.

22 Article Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma. 2017

Basturk, Olca / Berger, Michael F / Yamaguchi, Hiroshi / Adsay, Volkan / Askan, Gokce / Bhanot, Umesh K / Zehir, Ahmet / Carneiro, Fatima / Hong, Seung-Mo / Zamboni, Giuseppe / Dikoglu, Esra / Jobanputra, Vaidehi / Wrzeszczynski, Kazimierz O / Balci, Serdar / Allen, Peter / Ikari, Naoki / Takeuchi, Shoko / Akagawa, Hiroyuki / Kanno, Atsushi / Shimosegawa, Tooru / Morikawa, Takanori / Motoi, Fuyuhiko / Unno, Michiaki / Higuchi, Ryota / Yamamoto, Masakazu / Shimizu, Kyoko / Furukawa, Toru / Klimstra, David S. ·Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, Tokyo Medical University, Tokyo, Japan. · Department of Pathology, Emory University, Atlanta, GA, USA. · Department of Pathology, Centro Hospitalar São João/Faculty of Medicine of Porto University and Institute for Research and Innovation in Health/Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. · Department of Pathology, University of Verona, Ospedale S.C.-Don Calabria-Negrar, Verona, Italy. · New York Genome Center, Molecular Diagnostics, New York, NY, USA. · Department of Pathology, Colombia University Medical Center, New York, NY, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan. · Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. · Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan. · Department of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan. · Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan. ·Mod Pathol · Pubmed #28776573.

ABSTRACT: Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing. Three of these intraductal tubulopapillary neoplasms were also subjected to whole-genome sequencing. All intraductal tubulopapillary neoplasms revealed the characteristic histologic (cellular intraductal nodules of back-to-back tubular glands lined by predominantly cuboidal cells with atypical nuclei and no obvious intracellular mucin) and immunohistochemical (immunolabeled with MUC1 and MUC6 but were negative for MUC2 and MUC5AC) features. By genomic analyses, there was loss of CDKN2A in 5/20 (25%) of these cases. However, the majority of the previously reported intraductal papillary mucinous neoplasm-related alterations were absent. Moreover, in contrast to most ductal neoplasms of the pancreas, MAP-kinase pathway was not involved. In fact, 2/22 (9%) of intraductal tubulopapillary neoplasms did not reveal any mutations in the tested genes. However, certain chromatin remodeling genes (MLL1, MLL2, MLL3, BAP1, PBRM1, EED, and ATRX) were found to be mutated in 7/22 (32%) of intraductal tubulopapillary neoplasms and 27% harbored phosphatidylinositol 3-kinase (PI3K) pathway (PIK3CA, PIK3CB, INPP4A, and PTEN) mutations. In addition, 4/18 (18%) of intraductal tubulopapillary neoplasms had FGFR2 fusions (FGFR2-CEP55, FGFR2-SASS6, DISP1-FGFR2, FGFR2-TXLNA, and FGFR2-VCL) and 1/18 (5.5%) had STRN-ALK fusion. Intraductal tubulopapillary neoplasm is a distinct clinicopathologic entity in the pancreas. Although its intraductal nature and some clinicopathologic features resemble those of intraductal papillary mucinous neoplasm, our results suggest that intraductal tubulopapillary neoplasm has distinguishing genetic characteristics. Some of these mutated genes are potentially targetable. Future functional studies will be needed to determine the consequences of these gene alterations.

23 Article American Pancreatic Association and Japan Pancreas Society: Sisterhood Memorandum of Understanding. 2017

Go, Vay Liang W / Shimosegawa, Tooru / Saluja, Ashok K / Fuchs, Anna R / Takeuchi, Tadashi. ·From the *UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA; †Japan Pancreas Society, Tohoku University Graduate School of Medicine, Sendai, Japan; ‡American Pancreatic Association, University of Miami, Miami, FL; §Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA; and ∥Pancreas Research Foundation of Japan, Tokyo, Japan. ·Pancreas · Pubmed #28291160.

ABSTRACT: -- No abstract --

24 Article Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer. 2017

Yoshida, Naoki / Masamune, Atsushi / Hamada, Shin / Kikuta, Kazuhiro / Takikawa, Tetsuya / Motoi, Fuyuhiko / Unno, Michiaki / Shimosegawa, Tooru. ·Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: amasamune@med.tohoku.ac.jp. · Division of Hepato-Biliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. ·Cancer Lett · Pubmed #28093281.

ABSTRACT: Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined. SUIT-2 pancreatic cancer cells were subcutaneously injected into nude mice alone or with PSCs and the size of the tumors was monitored. Kindlin-2 expression was observed in PDAC and the peritumoral stroma. Stromal kindlin-2 expression was associated with shorter recurrence-free survival time after R0 resection. Knockdown of kindlin-2 resulted in decreased proliferation, migration, and cytokine expression in PSCs. The PSC-induced proliferation and migration of pancreatic cancer cells were suppressed by kindlin-2 knockdown in PSCs. In vivo, co-injection of PSCs increased the size of the tumors, but this effect was abolished by kindlin-2 knockdown in PSCs. In conclusion, kindlin-2 in PSCs promoted the progression of pancreatic cancer.

25 Article Exosomes Derived From Pancreatic Stellate Cells: MicroRNA Signature and Effects on Pancreatic Cancer Cells. 2017

Takikawa, Tetsuya / Masamune, Atsushi / Yoshida, Naoki / Hamada, Shin / Kogure, Takayuki / Shimosegawa, Tooru. ·From the Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. ·Pancreas · Pubmed #27841793.

ABSTRACT: OBJECTIVES: Pancreatic stellate cells (PSCs) interact with pancreatic cancer cells in the tumor microenvironment. Cell constituents including microRNAs may be exported from cells within membranous nanovesicles termed exosomes. Exosomes might play a pivotal role in intercellular communication. This study aimed to clarify the microRNA signature of PSC-derived exosomes and their effects on pancreatic cancer cells. METHODS: Exosomes were prepared from the conditioned medium of immortalized human PSCs. MicroRNAs were prepared from the exosomes and their source PSCs, and the microRNA expression profiles were compared by microarray. The effects of PSC-derived exosomes on proliferation, migration, and the mRNA expression profiles were examined in pancreatic cancer cells. RESULTS: Pancreatic stellate cell-derived exosomes contained a variety of microRNAs including miR-21-5p. Several microRNAs such as miR-451a were enriched in exosomes compared to their source PSCs. Pancreatic stellate cell-derived exosomes stimulated the proliferation, migration and expression of mRNAs for chemokine (C - X - C motif) ligands 1 and 2 in pancreatic cancer cells. The stimulation of proliferation, migration, and chemokine gene expression by the conditioned medium of PSCs was suppressed by GW4869, an exosome inhibitor. CONCLUSIONS: We clarified the microRNA expression profile in PSC-derived exosomes. Pancreatic stellate cell-derived exosomes might play a role in the interactions between PSCs and pancreatic cancer cells.

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