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Pancreatic Neoplasms: HELP
Articles by Masahiko Hirota
Based on 20 articles published since 2010
(Why 20 articles?)
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Between 2010 and 2020, Masahiko Hirota wrote the following 20 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Small solid pseudopapillary tumor of the pancreas in a 32-year-old man: report of a case. 2010

Mima, Kosuke / Hirota, Masahiko / Abe, Shinya / Iwatsuki, Masaaki / Imamura, Hiroshi / Tsuruzoe, Shu / Chikamoto, Akira / Tanaka, Hiroshi / Takamori, Hiroshi / Kanemitsu, Keiichiro / Tagami, Hirofumi / Honda, Yumi / Iyama, Kenichi / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. ·Surg Today · Pubmed #20676863.

ABSTRACT: A solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of a small SPT arising from the head of the pancreas in an asymptomatic 32-year-old man, plus a literature review of this tumor. A 32-year-old man was admitted to our department at Kumamoto University Hospital for the evaluation of a pancreatic mass. The tumor had central necrosis, which was poorly perfused on contrast-enhanced computed tomography (CT) and which had a high intensity on T2-weighted magnetic resonance imaging (MRI). Histology revealed the lesion to be a solid pseudopapillary tumor of the pancreas, with the characteristic pseudopapilla formation and central degeneration. However, no capsule formation was observed. The tumor was positive for CD56, CD10, alpha1-antitrypsin, alpha1-antichymotrypsin, beta-catenin, and progesterone receptor. However, the tumor was negative for pancreatic hormones, chromogranin-A, carcinoembryonic antigen, and carbohydrate antigen 19-9. We diagnosed the patient to have an SPT based on these histological findings. Small-sized solid pseudopapillary tumors of the pancreas are being increasingly recognized because of the recent advances in CT and MRI. We should also consider SPT even if it occurs in a male when the tumor contains necrosis-suspected areas which are poorly perfused on contrast-enhanced CT with a high intensity on T2-weighted MRI.

2 Clinical Trial No-touch pancreatectomy for invasive ductal carcinoma of the pancreas. 2014

Hirota, Masahiko / Ogawa, Michio. ·Kumamoto Regional Medical Center, Kumamoto, Japan. mhirota@krmc.or.jp. ·JOP · Pubmed #24865535.

ABSTRACT: BACKGROUND: Pancreatectomy is the only effective treatment for cancers of the pancreas. Surgeons usually grasp tumors during pancreatectomy; however, this procedure may increase the risk of squeezing and shedding of the cancer cells into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to overcome these problems, we have developed surgical techniques for no-touch pancreatectomy. METHODS: From April 2008 through September 2013, 52 patients have been operated on no-touch pancreatectomy for invasive ductal carcinoma of the pancreas by a single operator (M.H.). Among them, 40 received pancreatoduodenectomy (PD), and 12 did distal pancreatectomy (DP). Twenty two cases (42%) required SMV-PV resection. This is a study to see if pancreatectomy can be technically done using a no-touch surgical technique without deteriorating the post-operative prognosis. During the procedure, the pancreatic tumor is neither grasped nor squeezed by the surgeon. Furthermore, for improved dissection of the retroperitoneal tissue (leftward and posterior margins for PD and rightward and posterior margins for DP), we use a hanging and clamping maneuver and dissection behind Gerota fascia. RESULTS: Overall 2- and 5-year survival rates were 64 and 42% with mean follow-up periods of 34.4 months (range: 6-68 months). Recurrence free 2- and 5-year survival rates were 49 and 31%, respectively. The 5-year survival rates of patients with JPS-stage III and those with JPS-stage IV were 57 and 20%, respectively. The 5-year survival rates of patients with UICC-stage IIA and those with UICC- stage IIB were 49 and 39%, respectively. Patients with UICC-stage III or IV did not survive for more than 2 years. CONCLUSIONS: No-touch pancreatectomy has many theoretic advantages that merit further investigation in future randomized controlled trials.

3 Article Pancreatic cancer arising from the remnant pancreas after pancreatectomy: a multicenter retrospective study by the Kyushu Study Group of Clinical Cancer. 2019

Hashimoto, Daisuke / Arima, Kota / Nakagawa, Shigeki / Negoro, Yuji / Hirata, Toshihiko / Hirota, Masahiko / Inomata, Masafumi / Fukuzawa, Kengo / Ohga, Takefumi / Saeki, Hiroshi / Oki, Eiji / Yamashita, Yo-Ichi / Chikamoto, Akira / Baba, Hideo / Maehara, Yoshihiko. ·Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. · Department of Gastroenterological Surgery, Omuta Tenryo Hospital, 1-100 Tenryo, Omuta, 836-8566, Japan. · Department of Gastroenterology, Kochi Health Sciences Center, 2125 Ike, Kochi, 781-8555, Japan. · Department of Surgery, Japanese Red Cross Kumamoto Hospital, 2-1-1 Nagamine Minami, Higashi-ku, Kumamoto, 861-8520, Japan. · Department of Surgery, Kumamoto Regional Medical Center, 5-16-10 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. · Department of Gastroenterological and Pediatric Surgery, Oita University, Faculty of Medicine, 1-1-1 Idaigaoka, Hasama-machi, Oita, 879-5593, Japan. · Department of Surgery, Oita Red Cross Hospital, 3-2-37 Chiyo-cho, Oita, 870-0033, Japan. · Department of Surgery, Fukuoka Higashi Medical Center, 1-1-1 Chidori, Koga, 811-3195, Japan. · Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. · Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp. ·J Gastroenterol · Pubmed #30515563.

ABSTRACT: BACKGROUND: After initial pancreatic resection, local recurrence of pancreatic cancer (PC) or new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this retrospective study was to clarify the clinical features and establish a treatment strategy for remnant PC. METHODS: A multicenter retrospective study with the Kyushu Study Group of Clinical Cancer was carried out. Clinical data from 50 patients who developed remnant PC were analyzed. RAS mutation analysis of the initial tumor and of remnant PC was performed in 17 cases. RESULTS: The initial pancreatic resections were performed for 37 invasive ductal carcinomas, and for 13 other tumors. Thirty-seven patients underwent a second pancreatectomy for remnant PC (resected group), while thirteen patients were not operated (unresected group). The median overall survival times were 42.2 months in the resected group and 12.3 months in the unresected group (HR 0.374; 95% CI 0.17-0.83). In RAS mutation analysis, 14 cases had at least 1 missense variant of KRAS, HRAS, or NRAS in the initial pancreatic tumor and/or remnant PC. The same missense variants between the initial tumor and remnant PC were discovered only in KRAS of one patient, and in HRAS of one patient. No case had completely consistent missense variants between the initial tumor and remnant PC. CONCLUSIONS: This study found that repeated pancreatectomy for remnant PC can prolong patient survival, and RAS mutation analysis indicated that many remnant PCs are developed from metachronous multifocal origins.

4 Article PD-L1 expression enhancement by infiltrating macrophage-derived tumor necrosis factor-α leads to poor pancreatic cancer prognosis. 2019

Tsukamoto, Masayo / Imai, Katsunori / Ishimoto, Takatsugu / Komohara, Yoshihiro / Yamashita, Yo-Ichi / Nakagawa, Shigeki / Umezaki, Naoki / Yamao, Takanobu / Kitano, Yuki / Miyata, Tatsunori / Arima, Kota / Okabe, Hirohisa / Baba, Yoshifumi / Chikamoto, Akira / Ishiko, Takatoshi / Hirota, Masahiko / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan. · International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan. · Department of Cell Pathology, Kumamoto University, Kumamoto, Japan. · Department of Surgery, Kumamoto Regional Medical Center, Kumamoto, Japan. ·Cancer Sci · Pubmed #30426611.

ABSTRACT: Immunotherapy using anti-PD-1/PD-L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD-L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD-L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)-α upregulated PD-L1 expression in PDAC cells through NF-κB signaling. The induction of PD-L1 expression was also caused by co-culture with activated macrophages, and the upregulation was inhibited by neutralization with anti-TNF-α antibody after co-culture with activated macrophages. PD-L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD-L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8-positive T-cell infiltration. These findings indicate that tumor-infiltrating macrophage-derived TNF-α could be a potential therapeutic target for PDAC.

5 Article Significance of lymph node metastasis in pancreatic neuroendocrine tumor. 2017

Taki, Katsunobu / Hashimoto, Daisuke / Nakagawa, Shigeki / Ozaki, Nobuyuki / Tomiyasu, Shinjiro / Ohmuraya, Masaki / Arima, Kota / Kaida, Takayoshi / Higashi, Takaaki / Sakamoto, Keita / Sakata, Kazuya / Okabe, Hirohisa / Nitta, Hidetoshi / Hayashi, Hiromitsu / Chikamoto, Akira / Beppu, Toru / Takamori, Hiroshi / Hirota, Masahiko / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. · Department of Surgery, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Minami-ku, Kumamoto, 861-4193, Japan. · Department of Surgery, Kumamoto Regional Medical Center, 5-16-10 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. · Institute of Resources Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. · Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp. ·Surg Today · Pubmed #28229300.

ABSTRACT: PURPOSE: Pancreatic neuroendocrine tumor (PNET) is relatively rare and has a generally better prognosis than does pancreatic cancer. However, as its prognosis in patients with lymph node metastasis (LNM) is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of LNM in PNET. METHODS: We retrospectively examined 83 PNET patients who underwent pancreatic resections with lymph node dissection at Kumamoto University Hospital, Saiseikai Kumamoto Hospital, and Kumamoto Regional Medical Center from April 2001 to December 2014. Their clinicopathological parameters were analyzed by the absence or presence of LNM, and with regard to the disease-free survival (DFS) and overall survival (OS). A predictive score of LNM was also made using the age, tumor size, primary tumor location, and tumor function. RESULTS: Although the 5-year OS was 74.8% for LNM CONCLUSIONS: Although LNM was not an independent prognostic factor, lymph node dissection is recommended for patients whose predictive score is larger than 1.69.

6 Article Residual total pancreatectomy: Short- and long-term outcomes. 2016

Hashimoto, Daisuke / Chikamoto, Akira / Taki, Katsunobu / Arima, Kota / Yamashita, Yo-Ichi / Ohmuraya, Masaki / Hirota, Masahiko / Baba, Hideo. ·Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto City, Japan. Electronic address: daisukeh@kumamoto-u.ac.jp. · Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto City, Japan. · Institute of Resource Development and Analysis, Kumamoto University Graduate School of Medical Sciences, Kumamoto City, Japan. · Department of Surgery, Kumamoto Regional Medical Center, Kumamoto City, Japan. ·Pancreatology · Pubmed #27189919.

ABSTRACT: BACKGROUND/OBJECTIVES: Because of limited numbers of patients, there are limited data available regarding outcomes after residual total pancreatectomy (R-TP). This study aimed to assess outcomes after the R-TP vs the one-stage total pancreatectomy (O-TP), especially focused on the pancreatic adenocarcinoma cases. METHODS: From 2005 to 2014, all patients who underwent the R-TP (n = 8) and the O-TP (n = 12) for pancreatic primary malignancy were prospectively enrolled. RESULTS: The median time from the initial operation to the R-TP was 30 months. Ten patients in the O-TP group and 8 in the R-TP had pancreatic adenocarcinoma. Postoperative complications occurred in two O-TP patients and one R-TP patient. There was no in-hospital mortality. At 12 months after surgery, the median insulin dose was 27 U/day after the O-TP and 24 U/day after the R-TP, the median hemoglobin A1c was 7.2% after the O-TP and 6.9% after the R-TP. There was a significantly larger reduction in body weight after the O-TP than after the R-TP. Postoperative fatty liver disease occurred in about half of the patients in each group. In patients with pancreatic adenocarcinoma, the 2-year overall survival rate was not significantly different (68.6% after the O-TP vs 71.4% after the R-TP). CONCLUSIONS: Although the postoperative morbidity and nutritional statuses should be improved, these favorable short- and long-term outcomes demonstrate that the R-TP is a feasible procedure for patients with malignant tumor in the remnant pancreas.

7 Article Heterogeneity of KRAS Mutations in Pancreatic Ductal Adenocarcinoma. 2016

Hashimoto, Daisuke / Arima, Kota / Yokoyama, Naomi / Chikamoto, Akira / Taki, Katsunobu / Inoue, Risa / Kaida, Takayoshi / Higashi, Takaaki / Nitta, Hidetoshi / Ohmuraya, Masaki / Hirota, Masahiko / Beppu, Toru / Baba, Hideo. ·From the *Department of Gastroenterological Surgery and †Institute of Resource Development and Analysis, Kumamoto University Graduate School of Medical Sciences; and ‡Department of Surgery, Kumamoto Regional Medical Center, Kumamoto, Japan. ·Pancreas · Pubmed #26967456.

ABSTRACT: OBJECTIVES: Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are the most common and frequent changes observed in pancreatic cancer. This study aimed to determine the frequency and extent of intratumoral and metastatic lymph node KRAS mutation heterogeneity of resected pancreatic ductal adenocarcinoma. METHODS: Tumor tissues macrodissected from tumor centers, invasion fronts (n = 97), and lymph nodes (n = 11) were subjected to DNA extraction and mutation analysis of KRAS codons 12 and 13 by pyrosequencing. RESULTS: Activating mutations in codon 12 of KRAS were detected in 90 (92.8%) tumor centers. No mutations were detected in KRAS codon 13 in any patient. After a comparison of tumor centers and invasion fronts, intratumoral heterogeneity of KRAS was observed only in 4 (4.1%) cases. Additional invasion front tumor analysis revealed the same mutation status consistent with each tumor center. No heterogeneity was observed between primary tumors and metastatic lymph nodes. CONCLUSIONS: Intratumoral heterogeneity of the KRAS mutational status is rare in pancreatic ductal adenocarcinoma. In addition, no KRAS heterogeneity between primary tumors and metastatic lymph nodes was detected in this study. This finding is consistent with the hypothesis that oncogenic activation of KRAS is the first driver mutation in pancreatic cancer.

8 Article Retrospective analysis of short term outcomes after spleen-preserving distal pancreatectomy for sodid pseudopapillary tumours. 2015

Graziosi, Luigina / Marino, Elisabetta / Rivellini, Roberta / Ciaccio, Vincenzo / Cirocchi, Roberto / Sanguinetti, Alessandro / Hirota, Masahiko / Avenia, Nicola / Donini, Annibale. ·General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia. Electronic address: luiginagraziosi@yahoo.it. · General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia. Electronic address: elisabetta.marino1986@gmail.com. · General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia. Electronic address: roririvellini@gmail.com. · General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia. Electronic address: vincenzo.ciaccio@unipg.it. · Department of General and Oncologic Surgery, Santa Maria Hospital, University of Perugia, Terni. Electronic address: roberto.cirocchi@unipg.it. · Department of General Surgery, Santa Maria Hospital, University of Perugia, Terni. Electronic address: a.sanguinetti@aospterni.it. · Kumamoto Regional Medical Center, Japan. Electronic address: mhirota@krmc.or.jp. · Department of General Surgery, Santa Maria Hospital, University of Perugia, Terni. Electronic address: nicolaavenia@libero.it. · General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia. Electronic address: annibale.donini@unipg.it. ·Int J Surg · Pubmed #26118599.

ABSTRACT: Solid pseudopapillary pancreatic tumour (SPN) is a rare pancreatic tumour representing 0.1%-3% of all exocrine pancreatic tumours. Most SPN show benign and low-grade malignant behaviour; malignant degeneration is observed in 10-15% of the patients. More than 40% of SPN involve the tail of the pancreas leading to a minimal invasive distal pancreatectomy approach. In this report we present the case of a young 22 Caucasian woman suffering from SPN who successfully underwent laparoscopic spleen-preserving distal pancreatectomy. Postoperative course was uneventful. A CT scan control at six months was negative for recurrences. We have also made an analysis of all the laparoscopic treatment of SPN reported in English literature.

9 Article Can the measurement of amylase in drain after distal pancreatectomy predict post-operative pancreatic fistula? 2015

Cirocchi, Roberto / Graziosi, Luigina / Sanguinetti, Alessandro / Boselli, Carlo / Polistena, Andrea / Renzi, Claudio / Desiderio, Jacopo / Noya, Giuseppe / Parisi, Amilcare / Hirota, Masahiko / Donini, Annibale / Avenia, Nicola. ·Department of General and Oncologic Surgery, University of Perugia, Terni, Italy. Electronic address: roberto.cirocchi@unipg.it. · General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy. Electronic address: luiginagraziosi@yahoo.it. · Department of General Surgery, Saint Mary Hospital, University of Perugia, Terni, Italy. Electronic address: a.sanguinetti@aospterni.it. · Department of General and Oncologic Surgery, University of Perugia, Perugia, Italy. Electronic address: carloboselli@yahoo.it. · Department of General Surgery, Saint Mary Hospital, University of Perugia, Terni, Italy. Electronic address: apolis74@yahoo.it. · Department of General and Oncologic Surgery, University of Perugia, Perugia, Italy. Electronic address: renzicla@virgilio.it. · Department of General and Oncologic Surgery, University of Perugia, Terni, Italy. Electronic address: djdesi85@hotmail.it. · Department of General and Oncologic Surgery, University of Perugia, Perugia, Italy. Electronic address: giuseppe.noya@unipg.it. · Department of Digestive Surgery, St. Maria Hospital, Terni, Italy. Electronic address: amilcareparisi@virgilio.it. · Kumamoto Regional Medical Center, Japan. Electronic address: mhirota@krmc.or.jp. · General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy. Electronic address: annibale.donini@unipg.it. · Department of General Surgery, Saint Mary Hospital, University of Perugia, Terni, Italy. Electronic address: nicolaavenia@libero.it. ·Int J Surg · Pubmed #26117433.

ABSTRACT: INTRODUCTION: The most frequent reason for performing a distal pancreatectomy is the presence of cystic or neuroendocrine tumors, in which the distal pancreatic stump is often soft and non fibrotic. This parenchymal consistence represents the main risk factor for post-operative pancreatic fistula. In order to identify the fistula and assessing its severity postoperative monitoring of amylase from intraperitoneal drains is important. METHODS: From a retrospective multicentric database analysis were included 33 patients who underwent distal pancreatectomy for pancreatic neoplastic disease. RESULTS: Postoperative pancreatic fistula occurred in four cases. One patient had a ductal adenocarcinoma, two presented with pancreatic endocrine neoplasms and the last one had an intraductal papillary mucinous neoplasia. Two patients underwent open, the other two laparoscopic distal pancreatectomy. DISCUSSION: Postoperative pancreatic fistulas after distal pancreatectomy worsen the quality of life, prolong the post-operative stay and delay further adjuvant therapy. In patients who underwent distal pancreatectomy literature exposed some advantages deriving from the placement of abdominal drainages only in selected cases and from their early removal. Patients presenting a high risk of pancreatic fistula had higher amylase levels of drainage fluid in the first postoperative day. CONCLUSION: POPF is the most frequently complication after pancreatectomy. In our analysis DFA1>5000 can be considered as a predictive factor for pancreatic fistula. For this reason, the systematic measurement of amylase in drain fluid in first-postoperative day can be considered a good clinical practice.

10 Article Staging laparoscopy leads to rapid induction of chemotherapy for unresectable pancreatobiliary cancers. 2015

Hashimoto, Daisuke / Chikamoto, Akira / Sakata, Kazuya / Nakagawa, Shigeki / Hayashi, Hiromitsu / Ohmuraya, Masaki / Hirota, Masahiko / Yoshida, Naoya / Beppu, Toru / Baba, Hideo. ·Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. ·Asian J Endosc Surg · Pubmed #25598056.

ABSTRACT: Preoperatively evaluating the resectability of pancreatobiliary cancers is difficult. The aim of this study was to investigate the benefit of staging laparoscopy in unresectable pancreatobiliary cancers. Between 2010 and 2013, 25 patients with pancreatobiliary cancers underwent staging laparoscopy after conventional tumor staging; they were compared with 10 patients who had unresectable or metastatic tumors that were found during laparotomy. Staging laparoscopy did not show unresectable factors in 11 patients, and resections were performed in these patients. Unresectable factors were found in other 14 patients who underwent staging laparoscopy. In these patients, chemotherapy was started after median postoperative day 3 (range, 2-10 days). This period was significantly longer in patients who received unnecessary laparotomy; chemotherapy was started after median postoperative day 11 (range, 6-15 days). These results suggest that staging laparoscopy, while avoiding laparotomy with unsuccessful resection, can lead to rapid induction of chemotherapy for unresectable pancreatobiliary cancers.

11 Article Impact of Postoperative Weight Loss on Survival After Resection for Pancreatic Cancer. 2015

Hashimoto, Daisuke / Chikamoto, Akira / Ohmuraya, Masaki / Abe, Shinya / Nakagawa, Shigeki / Beppu, Toru / Takamori, Hiroshi / Hirota, Masahiko / Baba, Hideo. ·Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Japan. · Institute of Resource Development and Analysis, Kumamoto University Graduate School of Medical Sciences, Japan. · Department of Surgery, Saiseikai Kumamoto Hospital, Japan. · Department of Surgery, Kumamoto Regional Medical Center, Japan. · Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Japan hdobaba@kumamoto-u.ac.jp. ·JPEN J Parenter Enteral Nutr · Pubmed #24486859.

ABSTRACT: BACKGROUND: The aim of this study was to assess the effects of postoperative body weight loss on long-term survival after resection for pancreatic cancer. METHODS: A total of 93 patients with primary pancreatic cancer underwent pancreatic resection between April 2005 and December 2011. Patient characteristics, preoperative body mass index, and changes in postoperative body weight were evaluated retrospectively and correlated with long-term survival. RESULTS: There was no significant association between survival and preoperative body mass index. Body weight fell by 8.4% at 2 months after surgery and by 9.0% at 4 months after surgery. Severe postoperative body weight losses, both at 2 months (P = .033) and 4 months (P = .014) after surgery, were significantly associated with poor prognosis, especially among patients with stage IA-IIA pancreatic cancer (n = 43) (P = .005 at 2 months and P < .001 at 4 months). Additionally, severe body weight loss tended to be associated with shorter survival among patients with stage IIB-III pancreatic cancer (n = 50), although the difference was not significant. Multivariate analysis revealed that postoperative body weight loss was an independent prognostic factor. CONCLUSIONS: The results of this study demonstrated that pancreatic cancer patients with severe postoperative body weight loss have poorer postoperative outcomes.

12 Article EZH2 is associated with malignant behavior in pancreatic IPMN via p27Kip1 downregulation. 2014

Kuroki, Hideyuki / Hayashi, Hiromitsu / Okabe, Hirohisa / Hashimoto, Daisuke / Takamori, Hiroshi / Nakahara, Osamu / Nakagawa, Shigeki / Fukushima, Yukiko / Chikamoto, Akira / Beppu, Toru / Hirota, Masahiko / Iyama, Ken-ichi / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. · Department of Surgery, Kumamoto Regional Medical Center, Kumamoto, Japan. · Department of Surgical Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. ·PLoS One · Pubmed #25084021.

ABSTRACT: BACKGROUND: The epigenetic mechanism of tumorigenesis in pancreatic intraductal papillary mucinous neoplasm (IPMN) remains largely unknown. The aim of this study is to examine the role of enhancer of zeste homologue 2 (EZH2) alteration in pancreatic IPMN progression. METHODS: Fifty-four surgically resected pancreatic IPMN specimens, including a total of 181 lesions (normal duct in 48, adenoma in 50, borderline atypia in 53, carcinoma in situ (CIS) in 19, and invasive carcinoma in 11) were analyzed by immunohistochemical staining (EZH2, Ki-67, p27Kip1). Using paraffin embedded sections, total RNA was successfully extracted from 20 IPMN lesions (borderline IPMN in 9, CIS in 6, invasive carcinoma in 5) and 7 pancreatic normal ducts, and then levels of EZH2 and p27Kip1 mRNA were analyzed by real time PCR. RESULTS: In immunohistochemical analysis, cell proliferative activity revealed by Ki-67 positive nuclei was increased during IPMN progression (normal ductEZH2 is associated with the accelerated cell proliferation and malignant step in pancreatic IPMN via the downregulation of p27Kip1.

13 Article Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs. 2014

Hashimoto, Daisuke / Bläuer, Merja / Hirota, Masahiko / Ikonen, Niina H / Sand, Juhani / Laukkarinen, Johanna. ·Tampere Pancreas Laboratory, Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Teiskontie 35, P.O. Box 2000, 33521 Tampere, Finland; Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan. · Tampere Pancreas Laboratory, Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Teiskontie 35, P.O. Box 2000, 33521 Tampere, Finland. · Department of Surgery, Kumamoto Regional Medical Center, 5-16-10 Honjo, Kumamoto 860-0811, Japan. · Tampere Pancreas Laboratory, Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Teiskontie 35, P.O. Box 2000, 33521 Tampere, Finland. Electronic address: johanna.laukkarinen@fimnet.fi. ·Eur J Cancer · Pubmed #24503026.

ABSTRACT: BACKGROUND AND AIM: Autophagy is a regulated process of degradation and recycling of cellular constituents. The role of autophagy in pancreatic cancer is still not clear. Some studies indicate that in pancreatic cancer autophagy exerts cytoprotective effects, whereas others suggest that autophagy positively contributes to cell death by enhancing cytotoxicity of anticancer drugs. The aim of this study was to investigate the role of autophagy in pancreatic cancer, and to provide insights into new strategies for treatment. MATERIALS AND METHODS: Pancreatic cancer cell lines PANC-1 and BxPC-3 were treated with anticancer drugs (5-fluorouracil or gemcitabine) alone and in combination with autophagy inhibitors (chloroquine or wortmannin). Biopsy samples were retrieved from patients from pancreatic normal tissue and adenocarcinoma. Western blot of microtubule-associated protein 1 light chain 3 (LC3)-II was performed to investigate the degree of autophagy and cell proliferation was assessed by a crystal violet assay. RESULTS: Autophagy was active in PANC-1 cells under basal conditions. Autophagy was significantly induced in pancreatic ductal adenocarcinoma compared to healthy pancreatic tissue in patients. Inhibition of autophagy by chloroquine suppressed the growth of PANC-1 and BxPC-3. Autophagy was markedly increased after treatment with 5-fluorouracil or gemcitabine. Inhibition of autophagy by chloroquine potentiated the inhibition of cell proliferation of PANC-1 and BxPC-3 by 5-fluorouracil and gemcitabine. CONCLUSIONS: Our results with pancreatic cancer cell lines and human pancreatic adenocarcinoma suggest that autophagy contributes to pancreatic cancer cell growth. Autophagy has a cytoprotective effect against 5-fluorouracil and gemcitabine in pancreatic cancer cells. Combination therapy of these anticancer drugs and chloroquine should be investigated.

14 Article The modified Glasgow Prognostic Score (mGPS) is a good predictor of indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. 2014

Ikuta, Yoshiaki / Takamori, Hiroshi / Sakamoto, Yasuo / Hashimoto, Daisuke / Chikamoto, Akira / Kuroki, Hideyuki / Sakata, Kazuya / Sakamoto, Keita / Hayashi, Hiromitsu / Imai, Katsunori / Nitta, Hidetoshi / Hirota, Masahiko / Kanemitsu, Keiichiro / Beppu, Toru / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. ·Int J Clin Oncol · Pubmed #23999903.

ABSTRACT: BACKGROUND: Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. METHODS: Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. RESULTS: The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0-1 patients with an MST of 6.3 months. CONCLUSIONS: The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery.

15 Article Pancreatic cancer in the remnant pancreas following primary pancreatic resection. 2014

Hashimoto, Daisuke / Chikamoto, Akira / Ohmuraya, Masaki / Sakata, Kazuya / Miyake, Keisuke / Kuroki, Hideyuki / Watanabe, Masayuki / Beppu, Toru / Hirota, Masahiko / Baba, Hideo. ·Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. ·Surg Today · Pubmed #23975591.

ABSTRACT: PURPOSE: To clarify the clinical features of cancer in the pancreatic remnant. METHODS: We retrospectively reviewed the clinical and pathological findings of 10 patients who developed remnant pancreatic cancer in our hospital between 2002 and 2012. The KRAS sequences in both the initial pancreatic tumor and remnant pancreatic cancer were examined in two patients. RESULTS: Eight patients underwent a second pancreatectomy for remnant pancreatic cancer (resected group), while two patients were not operated on and underwent chemotherapy (unresected group). The remnant pancreatic cancer developed at the cut end of the pancreas (pancreaticogastrostomy site) in four patients. In the resected group, four patients died 17 months after the emergence of the remnant pancreatic cancer and four patients survived during the median 40.5-month observation period. The median survival of the unresected group after the emergence of the remnant pancreatic cancer was 10 months. The findings of the KRAS sequencing and immunohistological staining of the remnant pancreatic cancer for MUC1 and MUC2 in the two patients were consistent with those of the initial pancreatic tumor in one patient, and not consistent in the other. CONCLUSIONS: Our results suggest that both local recurrence and a new primary cancer can develop in the pancreatic remnant, and repeated pancreatectomy can prolong survival.

16 Article Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia. 2013

Ozaki, Nobuyuki / Ohmuraya, Masaki / Ida, Satoshi / Hashimoto, Daisuke / Ikuta, Yoshiaki / Chikamoto, Akira / Hirota, Masahiko / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. ·J Hepatobiliary Pancreat Sci · Pubmed #23475261.

ABSTRACT: BACKGROUND: Serine protease inhibitor Kazal type 1 (SPINK1) is expressed in normal human pancreatic acinar cells and in a variety of tumors, and binds to the epidermal growth factor receptor (EGFR), mediating cell proliferation through the mitogen-activated protein kinase cascade in pancreatic cancer cell lines. Here, we aimed to assess SPINK1 and EGFR expression in various neoplastic lesions, including tissues demonstrating precancerous changes. METHODS: Surgical specimens of pancreatic ductal adenocarcinoma (n = 23), intraductal papillary mucinous neoplasm (IPMN;n = 21), pancreatic neoplasms other than ductal adenocarcinoma (n = 8), chronic pancreatitis (n = 11), and pancreatic intraepithelial neoplasia (PanIN) lesions within the resected specimens were analyzed immunohistochemically for SPINK1 and EGFR expression. RESULTS: Sixty-five PanIN-1A, 32 PanIN-1B, 17 PanIN-2, and 6 PanIN-3 were identified. Both SPINK1 and EGFR were expressed in almost all PanIN lesions. All tubular ductal adenocarcinoma, IPMN, and mucinous cystadenocarcinoma samples (neoplasms of ductal origin) expressed SPINK1, whereas acinar cell carcinoma, anaplastic carcinoma, adenosquamous carcinoma, insulinoma, and islet cell carcinoma did not. EGFR was expressed in 87 % of tubular adenocarcinoma and 48 % of IPMN lesions. Among IPMN lesions, malignant lesions (IPMC) expressed EGFR more often than benign lesions (IPMA) did. Scattered expression of EGFR was observed in normal pancreatic ducts and within the tubular complex within chronic pancreatitis lesions. CONCLUSIONS: These results indicate that SPINK1 plays a role as a growth factor, signaling through the EGFR pathway in pancreatic ductal adenocarcinoma and neoplasms, and that the EGFR is involved in the malignant transformation of IPMN.

17 Article Perioperative intra-arterial and systemic chemotherapy for pancreatic cancer. 2011

Takamori, Hiroshi / Kanemitsu, Keiichiro / Hirota, Masahiko / Ikeda, Osamu / Tanaka, Hiroshi / Beppu, Toru / Yamashita, Yasuyuki / Oya, Natsuo / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. h-takamori@fc.kuh.kumamoto-u.ac.jp ·Ann Surg Oncol · Pubmed #21046268.

ABSTRACT: BACKGROUND: Even after curative resection of pancreatic cancer, there is a high probability of systemic recurrence. This indicates that subclinical metastases are already present at the time of operation. The purpose of this study was to assess the feasibility and outcomes of patients who received a novel multimodality therapy combining pancreatic resection and intraoperative radiation therapy (IORT) with pre- and postoperative chemotherapy for pancreatic cancer. METHODS: For eligible patients with pancreatic cancer, 5-FU was administered at a dose of 125 mg/m(2)/day on days 1-5 every week as a continuous pancreatic and hepatic arterial infusion, and gemcitabine was infused intravenously at a dose of 800 mg/m(2) per day once per week for 2 weeks for preoperative chemotherapy. Pancreatic resection combined with IORT was performed 1 week after preoperative chemotherapy. Postoperative chemotherapy was performed in the same way as preoperative chemotherapy. We performed an intention-to-treat analysis for all enrolled patients. RESULTS: This study enrolled 44 patients. The most common toxicities were hematological and gastrointestinal events. Grade 3/4 hematological toxicities were observed during preoperative chemotherapy, although there were no grade 3/4 nonhematological events. Postoperative chemotherapy-related toxicities were more critical and frequent than preoperative ones. There were no pre- or postoperative chemotherapy-associated deaths. Median overall survival was 36.5 months with 30.5% overall 5-year survival. CONCLUSIONS: This multimodality therapy is feasible and promises to contribute to survival. It should be evaluated in a phase III setting.

18 Article Nitric oxide inhibits the proliferation and invasion of pancreatic cancer cells through degradation of insulin receptor substrate-1 protein. 2010

Sugita, Hiroki / Kaneki, Masao / Furuhashi, Satoshi / Hirota, Masahiko / Takamori, Hiroshi / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. sugitaf@ba2.so-net.ne.jp ·Mol Cancer Res · Pubmed #20663861.

ABSTRACT: Nitric oxide (NO), which plays a role in the posttranslational modification of proteins, exhibits tumoricidal activity. However, the mechanism remains largely unclear. We investigated whether the regulation of insulin receptor substrate (IRS)-1 protein expression and insulin/insulin-like growth factor (IGF) signaling by NO is involved in the proliferation and invasion of pancreatic cancer cells. NO donor inhibited insulin/IGF-I-stimulated phosphorylation of insulin receptor/IGF-I receptor, IRS-1, Akt/PKB, and glycogen synthase kinase-3beta along with decreased expression of IRS-1 protein in MIAPaCa-2 cells, whereas NO donor enhanced the phosphorylation of extracellular signal-regulated kinase-1/2. In contrast, a selective inducible nitric oxide synthase inhibitor, 1400W, upregulated the expression of IRS-1 protein and the phosphorylation of IRS-1, Akt/PKB, and glycogen synthase kinase-3beta, along with enhanced proliferation and invasion of Panc-1 cells expressing inducible nitric oxide synthase protein. NO donor induced IRS-1 protein reduction through increased ubiquitination and degradation. For the detection of the site responsible for NO-induced ubiquitination, IRS-1 deletion mutant genes were transfected and overexpressed in MIAPaCa-2 cells. The results indicate that the COOH terminus of the IRS-1 protein is required for NO donor-induced ubiquitination and protein degradation. Cells stably transfected with COOH-terminal deletion mutants of IRS-1 exhibited reduced IGF signaling and cell proliferation compared with vector alone-transfected cells, with no influence of NO on IGF signaling and invasion, although stable transfectants with full-length IRS-1 protein exhibited remarkable NO-induced reduction in IGF signaling, cell proliferation, and invasion. These findings indicate that NO inhibits the proliferation and invasion of pancreatic cancer cells, at least in part, through upregulation of IRS-1 protein degradation and resultant downregulation of the insulin/IGF-I-Akt pathway.

19 Article The role of oxysterol binding protein-related protein 5 in pancreatic cancer. 2010

Ishikawa, Shinji / Nagai, Youhei / Masuda, Toshirou / Koga, Yoshikatsu / Nakamura, Tadahiko / Imamura, Yu / Takamori, Hiroshi / Hirota, Masahiko / Funakosi, Akihiro / Fukushima, Masakazu / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. ·Cancer Sci · Pubmed #20128820.

ABSTRACT: The expression of oxysterol binding protein-related protein (ORP) 5 is related to invasion and a poor prognosis in pancreatic cancer patients. ORP5 induced the expression of sterol response element binding protein (SREBP) 2 and activated the downstream gene of sterol response element. ChIP using SREBP2 antibody revealed that histone deacetylase 5 (HDAC5) was one of the downstream genes of SREBP2. The effect of HMG-CoA reductase inhibitors (statins) were analyzed according to the expression level of ORP5. The invasion rate and growth was suppressed in cells that strongly expressed ORP5 in a time- and dose-dependent manner, but had less effect in cells weakly expressing ORP5, suggesting that when the potential of invasion and growth relies on the cholesterol synthesis pathway, it becomes sensitive to HMG-CoA reductase inhibitor. Furthermore, HDAC inhibitor, tricostatin A, induced the expression of phosphatase and tensin homolog as well when ORP5 was suppressed or the cells were treated with statin. Treatment with both statin and tricostatin A showed a synergistic antitumor effect in cells that highly expressed ORP5. Therefore, in some pancreatic cancers, continuous ORP5 expression enhances the cholesterol synthesis pathway and this signal transduction regulates phosphatase and tensin homolog through HDAC5 expression. This is the first report to detail how the signal transduction of cholesterol synthesis is related to cancer invasion and why statins can suppress invasion and growth.

20 Article Clinical significance of dihydropyrimidine dehydrogenase and thymidylate synthase expression in patients with pancreatic cancer. 2010

Nakahara, Osamu / Takamori, Hiroshi / Tanaka, Hiroshi / Sakamoto, Yasuo / Ikuta, Yoshiaki / Furuhashi, Satoshi / Watanabe, Masayuki / Beppu, Toru / Hirota, Masahiko / Kanemitsu, Keiichiro / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan. ·Int J Clin Oncol · Pubmed #20072795.

ABSTRACT: BACKGROUND: Little is known about the clinical significance of TS and DPD in pancreatic cancer. We aimed to evaluate TS and DPD expression levels in not only pancreatic cancer but also surrounding normal pancreatic tissues to assess the clinical implications of the expression of TS and DPD in this study. PATIENTS AND METHODS: Pancreatic cancer and normal pancreatic tissues were obtained from 18 patients with pancreatic cancer who underwent pancreatic resection to measure TS and DPD activities. The TS and DPD activities were determined by enzyme-linked immunosorbent assay using non-fixed fresh-frozen specimens. RESULTS: Pancreatic cancer tissues had significantly higher DPD and TS enzyme activities than surrounding normal tissue. Anaplastic ductal carcinoma had higher DPD and TS activities than the other histological types. Patients with high DPD in this study demonstrated poorer prognosis than those with low DPD. On the other hand, there was no statistically significant difference in survival between the high and the low TS groups. CONCLUSIONS: The efficacy of 5-FU may be lower in pancreatic cancer tissue than in normal tissue because DPD activity is upregulated in pancreatic cancer tissue compared to normal pancreatic tissue. It is necessary to develop an effective 5-FU delivery system and/or 5-FU combined with an inhibitor for DPD that can be used when 5-FU must be administered to patients with pancreatic cancer. High DPD activity may be a prognostic factor in patients with pancreatic cancer.