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Pancreatic Neoplasms: HELP
Articles by Takao Ohtsuka
Based on 107 articles published since 2010
(Why 107 articles?)
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Between 2010 and 2020, Takao Ohtsuka wrote the following 107 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Review High-risk lesions in the remnant pancreas: fate of the remnant pancreas after pancreatic resection for pancreatic cancer and intraductal papillary mucinous neoplasms. 2019

Miyasaka, Yoshihiro / Ohtsuka, Takao / Matsuda, Ryota / Mori, Yasuhisa / Nakata, Kohei / Ohuchida, Kenoki / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. · Department of Surgery, Fukuoka University Chikushi Hospital, Chikushino, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. mnaka@surg1.med.kyushu-u.ac.jp. ·Surg Today · Pubmed #31346809.

ABSTRACT: Progress in diagnostic modalities, surgical procedures, and multidisciplinary treatment for pancreatic diseases has increased the number of long-term survivors after pancreatic resection. Several reports have focused on high-risk lesions (HRLs), including high-grade pancreatic intraepithelial neoplasia (PanIN), pancreatic ductal adenocarcinoma, high-grade intraductal papillary mucinous neoplasm (IPMN), and IPMN with an associated invasive carcinoma, in the remnant pancreas after partial pancreatic resection for pancreatic cancer or IPMN. The etiology of HRLs in the remnant pancreas is thought to be either isolated local recurrence of the initial lesion in the remnant pancreas or a newly developed primary lesion. Although it is difficult to distinguish between local recurrence and a new primary lesion, comparison of genetic alterations between two lesions may help with this distinction. Early detection of HRLs in the remnant pancreas may improve the prognosis of patients, and several investigators have proposed predictive factors for HRLs in the remnant pancreas after partial pancreatic resection for pancreatic cancer or IPMN. The reported short- and long-term outcomes of surgical resection of HRLs in the remnant pancreas are relatively favorable. Life-long surveillance of the remnant pancreas is recommended after partial pancreatic resection for pancreatic cancer or IPMN.

2 Review Neuroendocrine tumor of the pancreas with rhabdoid feature. 2018

Miyazaki, Tetsuyuki / Aishima, Shinichi / Fujino, Minoru / Ozono, Keigo / Kubo, Yuichiro / Ushijima, Yasuhiro / Osoegawa, Takashi / Ihara, Eikichi / Tetsuhide, Itou / Ohtsuka, Takao / Nakamura, Masafumi / Oda, Yoshinao. ·Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan. · Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. oda@surgpath.med.kyushu-u.ac.jp. ·Virchows Arch · Pubmed #29938394.

ABSTRACT: Imaging of a 53-year-old Japanese man revealed two tumors in the liver and a tumor in the head of the pancreas with a swelling lymph node. A needle biopsy for the liver tumors was performed, revealing a neuroendocrine tumor. Enucleation, lymphadenectomy, and partial hepatectomy were performed. The microscopic examination identified many tumor cells with intracytoplasmic inclusions arranged in a nested, cord, or tubular fashion. The intracytoplasmic inclusions displayed densely eosinophilic globules and displaced the nuclei toward the periphery, which constitutes "rhabdoid" features. The tumor cells were positive for synaptophysin and weakly positive for NCAM, but negative for chromogranin A. Epithelial markers (AE1/AE3 and CAM5.2) accentuated intracytoplasmic globules. Pancreatic neuroendocrine tumors with rhabdoid features are very rare. Generally, rhabdoid features are aggressive and dedifferentiated characteristics of various types of tumor. Pancreatic neuroendocrine tumors containing rhabdoid cells tend to display extrapancreatic spread at the time of presentation, although some of these tumors with rhabdoid features are not always associated with aggressive behavior.

3 Review Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. 2017

Tanaka, Masao / Fernández-Del Castillo, Carlos / Kamisawa, Terumi / Jang, Jin Young / Levy, Philippe / Ohtsuka, Takao / Salvia, Roberto / Shimizu, Yasuhiro / Tada, Minoru / Wolfgang, Christopher L. ·Department of Surgery, Shimonoseki City Hospital, Shimonoseki, Japan. Electronic address: masaotan@med.kyushu-u.ac.jp. · Pancreas and Biliary Surgery Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Department of Gastroenterology, Komagome Metropolitan Hospital, Tokyo, Japan. · Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea. · Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hopital Beaujon, Clichy Cedex, France. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Dept. of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan. · Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Cameron Division of Surgical Oncology and The Sol Goldman Pancreatic Cancer Research Center, Department of Surgery, Johns Hopkins University, Baltimore, MD, USA. ·Pancreatology · Pubmed #28735806.

ABSTRACT: The management of intraductal papillary mucinous neoplasm (IPMN) continues to evolve. In particular, the indications for resection of branch duct IPMN have changed from early resection to more deliberate observation as proposed by the international consensus guidelines of 2006 and 2012. Another guideline proposed by the American Gastroenterological Association in 2015 restricted indications for surgery more stringently and recommended physicians to stop surveillance if no significant change had occurred in a pancreatic cyst after five years of surveillance, or if a patient underwent resection and a non-malignant IPMN was found. Whether or not it is safe to do so, as well as the method and interval of surveillance, has generated substantial debate. Based on a consensus symposium held during the meeting of the International Association of Pancreatology in Sendai, Japan, in 2016, the working group has revised the guidelines regarding prediction of invasive carcinoma and high-grade dysplasia, surveillance, and postoperative follow-up of IPMN. As the working group did not recognize the need for major revisions of the guidelines, we made only minor revisions and added most recent articles where appropriate. The present guidelines include updated information and recommendations based on our current understanding, and highlight issues that remain controversial or where further research is required.

4 Review The up-to-date review of epidemiological pancreatic neuroendocrine tumors in Japan. 2015

Ito, Tetsuhide / Lee, Lingaku / Hijioka, Masayuki / Kawabe, Ken / Kato, Masaki / Nakamura, Kazuhiko / Ueda, Keijiro / Ohtsuka, Takao / Igarashi, Hisato. ·Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. itopapa@intmed3.med.kyushu-u.ac.jp. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·J Hepatobiliary Pancreat Sci · Pubmed #25689058.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) were considered an extremely rare disease. However, in recent years, the number of patients with PNET has increased rapidly. According to an epidemiological survey conducted in Japan, the number of treated patients with PNETs in 2010 was approximately 1.2-times that in 2005, and the number of new incidences of non-functional PNETs in 2010 was approximately 1.7-times that in 2005. Among functional PNETs, insulinoma was most prevalent, followed by gastrinoma. To diagnose PNETs, correct histological diagnosis is most important. According to the World Health Organization 2010 classification criteria, neuroendocrine tumors (NETs) are categorized into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NECs accounted for 7.6% of all NETs, and functional and non-functional PNETs accounted for 2.1% and 10.1%, respectively. Patients with distant metastasis accounted for 19.9%, and those with multiple endocrine neoplasia type 1 accounted for 4.3%. When treating PNETs, it is necessary to correctly evaluate the functionality and progression of tumors, the presence or absence of metastasis, and the degrees of differentiation and malignant potential of tumors. A new registration system from the Japan Neuroendocrine Tumor Society will start to be used in 2015, which will help further dissemination of Japanese epidemiological information to the world.

5 Review Follicular pancreatitis, report of a case clinically mimicking pancreatic cancer and literature review. 2014

Mizuuchi, Yusuke / Aishima, Shinichi / Hattori, Masami / Ushijima, Yasuhiro / Aso, Akira / Takahata, Shunichi / Ohtsuka, Takao / Ueda, Junji / Tanaka, Masao / Oda, Yoshinao. ·Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp. ·Pathol Res Pract · Pubmed #24476826.

ABSTRACT: We herein present a 71-year-old man who underwent pancreatoduodenectomy with the diagnosis of follicular pancreatitis. We could not completely deny malignancy by a preoperative imaging study. Endoscopic ultrasonography-guided fine needle aspiration biopsy demonstrated clusters of benign acinar cells and no proliferation of atypical lymphoid cells or rich plasma cells. Histologically, the prominent lymphoid follicle formation was seen in an ill-defined mass, 15 mm in size, in the pancreatic parenchyma. Duct-centered fibrotic rims were seen in the pancreatic ducts accompanied by mild fibrotic change between the follicles and obliterative phlebitis. No neoplastic epithelial cells were observed in the resected specimen, and infiltrating lymphocytes did not show any morphological atypia and monoclonal proliferation by immunohistochemical staining with B and T cell markers. In addition, we could exclude IgG4-related disease, because plasmacytic cells were rarely positive for IgG4. Although follicular pancreatitis is rare, this mass-forming inflammatory disease (pancreatitis) should be included in the preoperative differential diagnosis of pancreatic cancer.

6 Review Pancreatic Cancer: Clinical Significance of Biomarkers. 2013

Ohuchida, Kenoki / Ohtsuka, Takao / Mizumoto, Kazuhiro / Hashizume, Makoto / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Gastrointest Tumors · Pubmed #26675163.

ABSTRACT: BACKGROUND: Improvement in the prognosis of patients with pancreatic cancer, novel effective screening and diagnostic strategies and treatments are needed. Recent advances in the understanding of pancreatic carcinogenesis and tumor microenvironment have allowed identification of biomarkers for screening, diagnosis and prediction of cancer treatments, including novel therapies targeting specific cancer or stromal cell subpopulations. Personalized therapy in pancreatic cancer is also promising as several drugs such as S1, capecitabine and gemcitabine reportedly have significant therapeutic effects. Predictive markers are thus needed to select patients most likely to benefit from therapies based on gemcitabine or other drugs. SUMMARY: We review the clinical significance of promising screening, diagnostic, predictive and prognostic biomarkers based on genetic and epigenetic alterations and microRNA abnormalities in pancreatic cancer. We also review new types of biomarkers based on stromal cells, such as pancreatic stellate cells, in the microenvironment of pancreatic cancer.

7 Review [Pancreatic tumor: progress in diagnosis and treatment. Topics: III. Pancreatic endocrine tumor; 2. Current status of the treatment of pancreatic neuroendocrine tumors]. 2012

Ohtsuka, Takao / Tsutsumi, Kosuke / Ideno, Noboru / Takahata, Shunichi / Nakamura, Masafumi / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Japan. ·Nihon Naika Gakkai Zasshi · Pubmed #22413468.

ABSTRACT: -- No abstract --

8 Review [Present status and perspective in clinical research of pancreatic neuroendocrine tumor]. 2011

Ohtsuka, Takao / Tsutsumi, Kosuke / Takahata, Shunichi / Nakamura, Masafumi / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University. ·Nihon Rinsho · Pubmed #21834164.

ABSTRACT: -- No abstract --

9 Article S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer. 2019

Nakayama, Hiromichi / Ohuchida, Kenoki / Yonenaga, Akiko / Sagara, Akiko / Ando, Yohei / Kibe, Shin / Takesue, Shin / Abe, Toshiya / Endo, Sho / Koikawa, Kazuhiro / Okumura, Takashi / Shido, Koji / Miyoshi, Kei / Nakata, Kohei / Moriyama, Taiki / Miyasaka, Yoshihiro / Inoue, Shigetaka / Ohtsuka, Takao / Mizumoto, Kazuhiro / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. ·Int J Oncol · Pubmed #31180531.

ABSTRACT: Lymph node metastasis is an independent prognostic factor in pancreatic cancer. However, the mechanisms of lymph node colonization are unknown. As a mechanism of lymphatic metastasis, it has been reported for other types of cancer that spheroids from tumor cells cause circular chemorepellent‑induced defects (CCIDs) in lymphatic endothelial monolayers. In pancreatic cancer, such mechanisms of metastasis have not been elucidated. The present study evaluated the involvement of this new mechanism of metastasis in pancreatic cancer and investigated the associated factors. In human pancreatic cancer tissue, it was observed that clusters of cancer cells penetrated the wall of lymphatic ducts around the primary tumor. An in vitro co‑culture system was then used to analyze the mechanisms of tumor cell‑mediated disruption of lymphatic vessels. Time‑lapse microscopic imaging revealed that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. CCID formation ability differed depending on the cell line. Neither aggregation of spheroids nor adhesion to lymphatic endothelial cells (LECs) exhibited a significant correlation with this phenomenon. The addition of supernatant from cultured cancer cells enhanced CCID formation. Microarray analysis revealed that the expression of S100 calcium binding protein P (S100P) was significantly increased when LECs were treated with supernatant from cultured cancer cells. Addition of a S100P antagonist significantly suppressed the migration of LECs and CCID formation. The present findings demonstrated that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. These CCIDs in pancreatic cancer were partly regulated by S100P, suggesting that S100P may be a promising target to inhibit lymph node metastasis.

10 Article Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis. 2019

Yan, Zilong / Ohuchida, Kenoki / Fei, Shuang / Zheng, Biao / Guan, Weiyu / Feng, Haimin / Kibe, Shin / Ando, Yohei / Koikawa, Kazuhiro / Abe, Toshiya / Iwamoto, Chika / Shindo, Koji / Moriyama, Taiki / Nakata, Kohei / Miyasaka, Yoshihiro / Ohtsuka, Takao / Mizumoto, Kazuhiro / Hashizume, Makoto / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. kenoki@surg1.med.kyushu-u.ac.jp. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kenoki@surg1.med.kyushu-u.ac.jp. · Department of General Surgery, Shenzhen University General Hospital, Shenzhen, China. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Cancer Center of Kyushu University Hospital, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. mnaka@surg1.med.kyushu-u.ac.jp. ·J Exp Clin Cancer Res · Pubmed #31133044.

ABSTRACT: BACKGROUND: Extracellular signal-regulated kinases (ERKs) have been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer and colorectal cancer. ERK1/2 inhibitor can suppress growth of KRAS-mutant pancreatic tumors by targeting cancer cell. However, no studies have shown the expression of ERK1/2 on pancreatic stromal and its effect on pancreatic cancer-stromal interaction. METHODS: Immunohistochemistry and western blotting were performed to detect the expression of p-ERK1/2 in pancreatic tissues and cells. Cell viability assay was used to study IC50 of ERK inhibitor on pancreatic cancer cells (PCCs) and primary cancer-associated pancreatic stellate cells (PSCs). Transwell migration, invasion, cell viability assay, senescence β-galactosidase staining were performed to determine the effect of ERK inhibitor on PCCs and PSCs in vitro and in vivo. The expression of key factors involved in autophagy and epithelial-to-mesenchymal transition (EMT) process were evaluated by western blotting. The expression of key factors related to cell invasiveness and malignancy were confirmed by qRT-PCR. Co-transplantation of PCC Organoid and PSC using a splenic xenograft mouse model was used to evaluated combined treatment of ERK inhibitor and autophagy inhibitor. RESULTS: Immunohistochemical staining in pancreatic tumor samples and transgenetic mice detected p-ERK1/2 expression in both cancer cells and stromal cells. In pancreatic tissues, p-ERK1/2 was strongly expressed in cancer-associated PSCs compared with cancer cells and normal PSCs. PSCs were also significantly more sensitive to ERK1/2 inhibitor treatment. Inhibition of ERK1/2 suppressed EMT transition in HMPCCs, upregulated cellular senescence markers, activated autophagy in cancer-associated PSCs; and suppressed cancer-stromal interaction, which enhanced invasiveness and viability of cancer cells. We also found that chloroquine, an autophagy inhibitor, suppressed ERK inhibition-induced autophagy and promoted PSC cellular senescence, leading to significantly decreased cell proliferation. The combination of an ERK inhibitor and autophagy inhibitor suppressed liver metastasis in a splenic pancreatic cancer organoid xenograft mouse model. CONCLUSIONS: These data indicate that inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis.

11 Article Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer Potentially Improves Survival and Facilitates Surgery. 2019

Miyasaka, Yoshihiro / Ohtsuka, Takao / Kimura, Ryuichiro / Matsuda, Ryota / Mori, Yasuhisa / Nakata, Kohei / Kakihara, Daisuke / Fujimori, Nao / Ohno, Takamasa / Oda, Yoshinao / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mnaka@surg1.med.kyushu-u.ac.jp. ·Ann Surg Oncol · Pubmed #30868514.

ABSTRACT: BACKGROUND: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. METHODS: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. RESULTS: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). CONCLUSIONS: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients' prognosis and facilitates surgical procedures.

12 Article Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma. 2019

Nakamura, So / Sadakari, Yoshihiko / Ohtsuka, Takao / Okayama, Takafumi / Nakashima, Yohei / Gotoh, Yoshitaka / Saeki, Kiyoshi / Mori, Yasuhisa / Nakata, Kohei / Miyasaka, Yoshihiro / Onishi, Hideya / Oda, Yoshinao / Goggins, Michael / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Departments of Pathology, Medicine, and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mnaka@surg1.med.kyushu-u.ac.jp. ·Ann Surg Oncol · Pubmed #30820789.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Several studies have recently suggested that exosomes may have potential as novel biomarkers. This study aimed to isolate exosomes from pancreatic juice and to investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC. METHODS: Pancreatic juice was collected from patients with PDAC and chronic pancreatitis (CP) by endoscopic retrograde pancreatography. Exosomes were extracted by ultracentrifugation. The presence of exosomes was confirmed by electron microscopy and Western blotting using anti-CD63, -CD81, and -TSG101 antibodies. Relative levels of ex-miR-21 and ex-miR-155 were quantified and compared between PDAC and CP patients. RESULTS: A total of 35 pancreatic juice samples (27 PDAC and 8 CP) were collected. Relative levels of both ex-miR-21 and ex-miR-155 were significantly higher in PDAC patients compared with CP patients (p < 0.001 and p = 0.008, respectively). By contrast, no significant difference was apparent in relative levels of miR-21 and miR-155 in whole pancreatic juice from PDAC patients compared with CP patients (p = 0.08 and p = 0.61, respectively). Ex-miR-21 and ex-miR-155 levels discriminated PDAC patients from CP patients with area under the curve values of 0.90 and 0.89, respectively. The accuracies of ex-miR-21 levels, ex-miR-155 levels, and pancreatic juice cytology were 83%, 89%, and 74%, respectively. When combining the results of ex-miR profiling with pancreatic juice cytology, the accuracy was improved to 91%. CONCLUSIONS: We successfully extracted exosomes from pancreatic juice. Ex-miRs, including ex-miR-21 and ex-miR-155, in pancreatic juice may be developed as biomarkers for PDAC.

13 Article CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis. 2019

Yan, Zilong / Ohuchida, Kenoki / Zheng, Biao / Okumura, Takashi / Takesue, Shin / Nakayama, Hiromichi / Iwamoto, Chika / Shindo, Koji / Moriyama, Taiki / Nakata, Kohei / Miyasaka, Yoshihiro / Ohtsuka, Takao / Mizumoto, Kazuhiro / Oda, Yoshinao / Hashizume, Makoto / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. kenoki@surg1.med.kyushu-u.ac.jp. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kenoki@surg1.med.kyushu-u.ac.jp. · Department of General Surgery, Shenzhen University General Hospital, Shenzhen, China. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Cancer Center, Kyushu University Hospital, Fukuoka, Japan. · Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·J Cancer Res Clin Oncol · Pubmed #30770989.

ABSTRACT: PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer. METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model. RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model. CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.

14 Article Significance of neoadjuvant therapy for borderline resectable pancreatic cancer: a multicenter retrospective study. 2019

Kurahara, Hiroshi / Shinchi, Hiroyuki / Ohtsuka, Takao / Miyasaka, Yoshihiro / Matsunaga, Taketo / Noshiro, Hirokazu / Adachi, Tomohiko / Eguchi, Susumu / Imamura, Naoya / Nanashima, Atsushi / Sakamoto, Kazuhiko / Nagano, Hiroaki / Ohta, Masayuki / Inomata, Masafumi / Chikamoto, Akira / Baba, Hideo / Watanabe, Yusuke / Nishihara, Kazuyoshi / Yasunaga, Masafumi / Okuda, Koji / Natsugoe, Shoji / Nakamura, Masafumi. ·Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. h-krhr@m3.kufm.kagoshima-u.ac.jp. · Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. · Surgery and Oncology, Kyushu University, Fukuoka, 812-8582, Japan. · Surgery, Saga University, Saga, 849-8501, Japan. · Surgery, Nagasaki University, Nagasaki, 852-8501, Japan. · Hepato-Biliary-Pancreas Surgery, Miyazaki University, Miyazaki, 889-1692, Japan. · Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Yamaguchi, Japan. · Gastroenterological and Pediatric Surgery, Oita University, Oita, 879-5593, Japan. · Gastroenterological Surgery, Kumamoto University, Kumamoto, 860-0811, Japan. · Surgery, Kitakyushu Municipal Medical Center, Fukuoka, 802-0077, Japan. · Gastroenterological Surgery, Department of Medicine, Kurume University, Kurume, 830-0011, Japan. ·Langenbecks Arch Surg · Pubmed #30649607.

ABSTRACT: PURPOSE: Neoadjuvant therapy (NAT) is increasingly used to improve the prognosis of patients with borderline resectable pancreatic cancer (BRPC) albeit with little evidence of its advantage over upfront surgical resection. We analyzed the prognostic impact of NAT on patients with BRPC in a multicenter retrospective study. METHODS: Medical data of 165 consecutive patients who underwent treatment for BRPC between January 2010 and December 2014 were collected from ten institutions. We defined BRPC according to the National Comprehensive Cancer Network guidelines, and subclassified patients according to venous invasion alone (BR-PV) and arterial invasion (BR-A). RESULTS: The rates of NAT administration and resection were 35% and 79%, respectively. There were no significant differences in resection rates and prognoses between patients in the BR-PV and BR-A subgroups. NAT did not have a significant impact on prognosis according to intention-to-treat analysis. However, in patients who underwent surgical resection, NAT was independently associated with longer overall survival (OS). The median OS of patients who underwent resection after NAT (53.7 months) was significantly longer than that of patients who underwent upfront (17.8 months) or no resection (14.9 months). The rates of superior mesenteric or portal vein invasion, lymphatic invasion, venous invasion, and lymph node metastasis were significantly lower in patients who underwent resection after NAT than in those who underwent upfront resection despite similar baseline clinical profiles. CONCLUSIONS: Resection after NAT in patients with BRPC is associated with longer OS and lower rates of both invasion to the surrounding tissues and lymph node metastasis.

15 Article Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion. 2019

Kibe, Shin / Ohuchida, Kenoki / Ando, Yohei / Takesue, Shin / Nakayama, Hiromichi / Abe, Toshiya / Endo, Sho / Koikawa, Kazuhiro / Okumura, Takashi / Iwamoto, Chika / Shindo, Koji / Moriyama, Taiki / Nakata, Kohei / Miyasaka, Yoshihiro / Shimamoto, Masaya / Ohtsuka, Takao / Mizumoto, Kazuhiro / Oda, Yoshinao / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: kenoki@surg1.med.kyushu-u.ac.jp. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Endoscopic Diagnostics and Therapeutics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Kyushu University Hospital Cancer Center, Fukuoka, Japan. · Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: mnaka@surg1.med.kyushu-u.ac.jp. ·Cancer Lett · Pubmed #30590101.

ABSTRACT: The pancreas is an organ prone to inflammation, fibrosis, and atrophy because of an abundance of acinar cells that produce digestive enzymes. A characteristic of pancreatic cancer is the presence of desmoplasia, inflammatory cell infiltration, and cancer-associated acinar atrophy (CAA) within the invasive front. CAA is characterized by a high frequency of small ducts and resembles acinar-to-ductal metaplasia (ADM). However, the clinical significance of changes in acinar morphology, such as ADM with acinar atrophy, within the tumor microenvironment remains unclear. Here, we find that ADM within the invasive front of tumors is associated with cell invasion and desmoplasia in an orthotopic mouse model of pancreatic cancer. An analysis of resected human tumors revealed that regions of cancer-associated ADM were positive for TGFα, and that this TGFα expression was associated with primary tumor size and shorter survival times. Gene expression analysis identified distinct phenotypic profiles for cancer-associated ADM, sporadic ADM and chronic pancreatitis ADM. These findings suggest that the mechanisms driving ADM differ according to the specific tissue microenvironment and that cancer-associated ADM and acinar atrophy contribute to tumor cell invasion of the local pancreatic parenchyma.

16 Article Clinicopathological characteristics of non-functioning cystic pancreatic neuroendocrine tumors. 2019

Nakashima, Yohei / Ohtsuka, Takao / Nakamura, So / Mori, Yasuhisa / Nakata, Kohei / Miyasaka, Yoshihiro / Ishigami, Kosei / Matsuda, Ryota / Oda, Yoshinao / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: takao-o@surg1.med.kyushu-u.ac.jp. · Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: mnaka@surg1.med.kyushu-u.ac.jp. ·Pancreatology · Pubmed #30497875.

ABSTRACT: BACKGROUND/OBJECTIVES: The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component. METHODS: The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed. RESULTS: Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, P < 0.05) and cystic PNETs were significantly larger than solid PNETs (25 mm vs. 17 mm, P < 0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, P = 0.64), hepatic metastasis (7% vs. 3%, P = 0.54), or disease-free survival rate (both 86%, P = 0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, P < 0.01). CONCLUSIONS: Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively.

17 Article Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas: Metachronous multifocal lesion or local recurrence? 2019

Gotoh, Yoshitaka / Ohtsuka, Takao / Nakamura, So / Shindo, Koji / Ohuchida, Kenoki / Miyasaka, Yoshihiro / Mori, Yasuhisa / Mochidome, Naoki / Oda, Yoshinao / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: takao-o@surg1.med.kyushu-u.ac.jp. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Surgery · Pubmed #30497813.

ABSTRACT: BACKGROUND: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. METHODS: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes-KRAS, TP53, CDKN2A, and SMAD4-associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. RESULTS: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. CONCLUSION: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence.

18 Article Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix. 2019

Okumura, Takashi / Ohuchida, Kenoki / Kibe, Shin / Iwamoto, Chika / Ando, Yohei / Takesue, Shin / Nakayama, Hiromichi / Abe, Toshiya / Endo, Sho / Koikawa, Kazuhiro / Sada, Masafumi / Horioka, Kohei / Mochidome, Naoki / Arita, Makoto / Moriyama, Taiki / Nakata, Kohei / Miyasaka, Yoshihiro / Ohtsuka, Takao / Mizumoto, Kazuhiro / Oda, Yoshinao / Hashizume, Makoto / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Materials Science and Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan. ·Int J Cancer · Pubmed #30152542.

ABSTRACT: Although recent studies revealed that adipose tissue accelerates pancreatic tumor progression with excessive extracellular matrix, key players for desmoplasia in the adipose microenvironment remains unknown. Here, we investigated the roles of adipose tissue-derived stromal cells (ASCs) in desmoplastic lesions and tumor progression by in vitro and in vivo experiments. In a three-dimensional (3-D) organotypic fat invasion model using visceral fat from CAG-EGFP mice, GFP-positive fibroblastic cells infiltrated toward cancer cells. When tumor cells were inoculated into transplanted visceral fat pads in vivo, tumor weights and stromal components were enhanced compared to subcutaneous and orthotopic tumor cells inoculated without fat pads. Expression of αSMA in established human ASCs was lower compared to cancer associated fibroblasts, and the 3-D collagen matrices produced by ASCs cultured in cancer cell-conditioned medium changed from loose to dense structures that affected the motility of cancer cells. Microarray analyses revealed upregulation of S100A4 in ASCs, while S100A4-positive stromal cells were observed at extrapancreatic invasion sites of human pancreatic cancer. The present findings indicate that ASCs are recruited to extrapancreatic invasion sites and produce dense collagen matrices that lead to enhanced tumor progression. Both inhibition of ASCs recruitment and activation could lead to a novel antistromal therapy.

19 Article Differential Diagnosis of Pancreatic Epidermoid Cyst Without a Solid Component (Residual Splenic Tissue) vs. Mucinous Cystic Neoplasm. 2019

Ishigami, Kousei / Nishie, Akihiro / Irie, Hiroyuki / Asayama, Yoshiki / Ushijima, Yasuhiro / Takayama, Yukihisa / Okamoto, Daisule / Fujita, Nobuhiro / Ohtsuka, Takao / Ito, Tetsuhide / Mochidome, Naoki / Honda, Hiroshi. ·Department Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-8582, Japan. ishigami@radiol.med.kyushu-u.ac.jp. · Department Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-8582, Japan. · Department of Radiology, Faculty of Medicine and Graduate School of Medicine, Saga University, Saga, Japan. · Department Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan. · Department Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan. · Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan. ·J Gastrointest Cancer · Pubmed #29218653.

ABSTRACT: PURPOSE: The purpose of this study was to clarify whether there are differences in imaging findings between pancreatic epidermoid cyst (EDC) without a solid component (residual splenic tissue) and mucinous cystic neoplasm (MCN). MATERIALS AND METHODS: The study group consisted of histologically proven EDC (eight cases) and MCN (20 cases). CT and MRI findings were compared on the following imaging findings: the shape of the cystic lesions and the presence or absence of septum, calcification, and high-intensity fluid on T1- and diffusion-weighted images (b factor = 1000). The degree of contact with the pancreatic tail was compared between the EDCs and six of the MCNs at the edge of the pancreatic tail. RESULTS: The EDCs were round (n = 3) or oval (n = 5), while the MCNs consisted of three round, five oval, six pear-like, and six multilobulated lesions (P < 0.05). Septum was present in 4 of 8 (50%) EDCs and 19 of 20 (95%) MCNs (P < 0.05). The presence of calcification (2 of 8 [25%] EDCs vs. 8 of 20 [40%] MCNs), high-intensity fluid on T1-weighted images (2 of 7 [29%] EDCs vs. 5 of 20 [25%] MCNs), and high-intensity fluid on diffusion-weighted images (5 of 7 [71%] EDCs vs. 5 of 20 [25%] MCNs) were not significantly different. The degree of contact with the pancreatic parenchyma was similar between the two types of lesions. CONCLUSION: Although the imaging findings for EDC without a solid component and MCN overlap, a pear-like or multilobulated shape may favor a diagnosis of MCN.

20 Article Prognostic Value of Preoperative Nutritional and Immunological Factors in Patients with Pancreatic Ductal Adenocarcinoma. 2018

Abe, Toshiya / Nakata, Kohei / Kibe, Shin / Mori, Yasuhisa / Miyasaka, Yoshihiro / Ohuchida, Kenoki / Ohtsuka, Takao / Oda, Yoshinao / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mnaka@surg1.med.kyushu-u.ac.jp. ·Ann Surg Oncol · Pubmed #30225838.

ABSTRACT: BACKGROUND: Preoperative nutritional and immunological patient factors have been found to be associated with prognostic outcomes of malignant tumors; however, the clinical significance of these factors in pancreatic ductal adenocarcinoma (PDAC) remains controversial. OBJECTIVE: The aim of this study was to evaluate the prognostic value of nutritional and immunological factors in predicting survival of patients with PDAC. METHODS: Retrospective studies of 329 patients who underwent surgical resection for PDAC and 95 patients who underwent palliative surgery were separately conducted to investigate the prognostic impact of tumor-related factors and patient-related factors, including Glasgow Prognostic Score (GPS), modified GPS, Prognostic Nutritional Index (PNI), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, and lymphocyte/monocyte ratio. RESULTS: In multivariate analysis for patients with surgical resection for PDAC, PNI was an independent factor for overall survival (OS) and disease-free survival. The median OS of patients with PNI ≤ 45 was significantly shorter than that of patients with PNI > 45 (17.5 and 36.2 months, respectively; p < 0.001). In multivariate analysis for patients undergoing palliative surgery for PDAC, only NLR was an independent prognosis factor. The median OS of patients with NLR > 5 was significantly shorter than that of patients with NLR ≤ 5 (2.7 and 8.9 months, respectively; p < 0.001). CONCLUSIONS: PNI in patients with surgical resection and NLR in patients with palliative surgery for PDAC may be useful prognostic factors.

21 Article Minimally invasive preservation versus splenectomy during distal pancreatectomy: a systematic review and meta-analysis. 2018

Nakata, Kohei / Shikata, Satoru / Ohtsuka, Takao / Ukai, Tomohiko / Miyasaka, Yoshihiro / Mori, Yasuhisa / Velasquez, Vittoria Vanessa D M / Gotoh, Yoshitaka / Ban, Daisuke / Nakamura, Yoshiharu / Nagakawa, Yuichi / Tanabe, Minoru / Sahara, Yatsuka / Takaori, Kyoichi / Honda, Goro / Misawa, Takeyuki / Kawai, Manabu / Yamaue, Hiroki / Morikawa, Takanori / Kuroki, Tamotsu / Mou, Yiping / Lee, Woo-Jung / Shrikhande, Shailesh V / Tang, Chung Ngai / Conrad, Claudius / Han, Ho-Seong / Chinnusamy, Palanivelu / Asbun, Horacio J / Kooby, David A / Wakabayashi, Go / Takada, Tadahiro / Yamamoto, Masakazu / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Mie Prefectural Ichishi Hospital, Tsu-Shi, Mie, Japan. · Department of Community Medicine, Mie University School of Medicine, Tsu, Mie, Japan. · Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. · Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan. · Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan. · Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan. · Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. · Department of Surgery, Tokyo Jikei University School of Medicine, Tokyo, Japan. · Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan. · Department of Surgery, Tohoku University, Sendai, Japan. · Department of Surgery, National Hospital Nagasaki Medical Center, Nagasaki, Japan. · Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, China. · Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea. · Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea. · Division of Gastrointestinal Surgery and Minimal Access Surgery, GEM Hospital and Research Centre, Coimbatore, India. · Department of Surgery, Mayo Clinic, Jacksonville, FL, USA. · Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. · Department of Surgery, Ageo Central General Hospital, Ageo, Japan. · Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan. · Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan. ·J Hepatobiliary Pancreat Sci · Pubmed #29943909.

ABSTRACT: BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) has gained in popularity recently. However, there is no consensus on whether to preserve the spleen or not. In this study, we compared MIDP outcomes between spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS); as well as outcomes between splenic vessel preservation (SVP) and Warshaw's technique (WT). METHODS: A systematic search of PubMed (MEDLINE) and Cochrane Library was conducted and the reference lists of review articles were hand-searched. RESULTS: Fifteen relevant studies with 769 patients were selected for meta-analyses of DPS and SPDP, while another 15 studies with 841 patients were used for the analysis between SVP and WT. Compared with the DPS group, SPDP patients had significantly lower incidences of infectious complications (P = 0.006) and pancreatic fistula (P = 0.002), shorter operative time (P < 0.001), and less blood loss (P = 0.01). Compared with WT, SVP patients had significantly lower incidences of splenic infarction (P < 0.001) and secondary splenectomy (P = 0.003). Subanalysis for laparoscopic surgery alone had similar results. CONCLUSIONS: Based on this study, SPDP has significantly superior outcomes compared to DPS. When a spleen is preserved, SVP has better outcomes over WT for reducing splenic complications.

22 Article Role of SpyGlass-DS 2018

Ohtsuka, Takao / Gotoh, Yoshitaka / Nakashima, Yohei / Okayama, Yoshifumi / Nakamura, So / Morita, Makiko / Aly, Mohammed Y F / Velasquez, Vittoria Vanessa D M / Mori, Yasuhisa / Sadakari, Yoshihiko / Nakata, Kohei / Miyasaka, Yoshihiro / Ishigami, Kousei / Fujimori, Nao / Mochidome, Naoki / Oda, Yoshinao / Shimizu, Shuji / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: takao-o@surg1.med.kyushu-u.ac.jp. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · International Medical Department, Kyushu University Hospital, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: mnaka@surg1.med.kyushu-u.ac.jp. ·Pancreatology · Pubmed #29730245.

ABSTRACT: BACKGROUND/OBJECTIVES: It is often difficult to determine an adequate resection line during pancreatectomy for intraductal papillary mucinous neoplasm involving the main pancreatic duct during partial pancreatectomy. The aim of this study was to evaluate the usefulness of improved peroral pancreatoscopy using SpyGlass-DS METHODS: We collected and retrospectively analyzed clinicopathological data from seven consecutive patients who underwent preoperative assessment of intraductal papillary mucinous neoplasm involving the main duct using SpyGlass-DS RESULTS: Good imaging quality of the intraductal protruding lesion was obtained in all seven patients, and only one adverse event was noted wherein a patient had mild pancreatitis. Six patients underwent pancreatectomy. In one patient, masked-type concomitant pancreatic ductal adenocarcinoma and low-length dysplastic lesion was found near the surgical margin, which was not detected by preoperative imaging modalities including SpyGlass-DS CONCLUSIONS: SpyGlass-DS

23 Article Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma. 2018

Koikawa, Kazuhiro / Ohuchida, Kenoki / Ando, Yohei / Kibe, Shin / Nakayama, Hiromichi / Takesue, Shin / Endo, Sho / Abe, Toshiya / Okumura, Takashi / Iwamoto, Chika / Moriyama, Taiki / Nakata, Kohei / Miyasaka, Yoshihiro / Ohtsuka, Takao / Nagai, Eishi / Mizumoto, Kazuhiro / Hashizume, Makoto / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: kenoki@surg1.med.kyushu-u.ac.jp. · Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: mnaka@surg1.med.kyushu-u.ac.jp. ·Cancer Lett · Pubmed #29580808.

ABSTRACT: Stroma invasion is an important step in pancreatic cancer progression. However, how pancreatic ductal adenocarcinoma (PDAC) with ductal structure invades the surrounding stroma has not been clear. Here, we elucidated the mechanism of stromal invasion of PDAC, using organoids. From resected PDAC specimens, we established human PDAC organoids, which developed ductal and basement membrane (BM) structures. When the organoids were co-cultured with pancreatic stellate cells (PSCs) in a collagen matrix, organoids lost their BM and ductal structures, and invaded collagen matrix more frequently than did mono-cultured organoids. Interestingly, direct contact by PSCs to PDAC organoids was observed before BM destruction. Matrix metalloproteinase (MMP) 2 or membrane type-1 MMP (MT1MMP) knockdown in PSCs significantly attenuated BM destruction by PSCs, and retained the ductal structures in organoids. Our results imply that direct contact by PSCs induces BM destruction and stromal invasion of PDAC via MMP2 which binds to MT1MMP on PSCs.

24 Article Surveillance of patients with intraductal papillary mucinous neoplasm with and without pancreatectomy with special reference to the incidence of concomitant pancreatic ductal adenocarcinoma. 2018

Date, Kenjiro / Ohtsuka, Takao / Nakamura, So / Mochidome, Naoki / Mori, Yasuhisa / Miyasaka, Yoshihiro / Oda, Yoshinao / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: takao-o@surg1.med.kyushu-u.ac.jp. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: mnaka@surg1.med.kyushu-u.ac.jp. ·Surgery · Pubmed #29221879.

ABSTRACT: BACKGROUND: The presence of an intraductal papillary mucinous neoplasm is important in the detection of concomitant pancreatic ductal adenocarcinoma. The aim of this study was to elucidate the incidence and timing of development of concomitant pancreatic ductal adenocarcinoma in patients with and without pancreatectomy for intraductal papillary mucinous neoplasm. METHODS: We reviewed retrospectively the surveillance data for 22 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm (pancreatic ductal adenocarcinoma-resection group), 180 who underwent pancreatectomy for intraductal papillary mucinous neoplasm (intraductal papillary mucinous neoplasm-resection group), and 263 whose intraductal papillary mucinous neoplasms were left untreated (nonresection group). The incidence and timing of the development of a concomitant pancreatic ductal adenocarcinoma during the surveillance of patients with and without partial pancreatectomy for intraductal papillary mucinous neoplasm were investigated using the Kaplan-Meier method. RESULTS: During a median surveillance period of 40 months (range 6-262 months), 5 patients in the pancreatic ductal adenocarcinoma-resection group, 6 in the intraductal papillary mucinous neoplasm-resection group, and 8 in the nonresection group developed concomitant pancreatic ductal adenocarcinoma. The estimated 5-year (17%) and 10-year (56%) cumulative incidences of secondary pancreatic ductal adenocarcinoma in the pancreatic ductal adenocarcinoma-resection group were significantly greater than those in the other two groups (P < .01). Conversely, the difference in the estimated cumulative incidence of concomitant pancreatic ductal adenocarcinoma between the intraductal papillary mucinous neoplasm-resection and nonresection groups was not significant (5-year, 5.0% vs 2.2%; 10-year, 5.0% vs 8.7%; P = .87). CONCLUSION: Long-term (≥5-year) surveillance in patients with intraductal papillary mucinous neoplasm is necessary and important because of the potential for development of concomitant pancreatic ductal adenocarcinoma. Those with a history of resection of concomitant pancreatic ductal adenocarcinoma at the time of the initial operation are at quite high risk for the development of secondary pancreatic ductal adenocarcinoma.

25 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 / Anonymous7560927. ·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.

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