研究者詳細 - 水口　徹

論文 - 水口　徹

分割表示 156 件中 41 - 60 件目／全件表示 >>

ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway

Tadashi Ogawa, Yoshihiko Hirohashi, Aiko Murai, Toshihiko Nishidate, Kenji Okita, Liming Wang, Yuzuru Ikehara, Tetsuta Satoyoshi, Akihiro Usui, Terufumi Kubo, Munehide Nakastugawa, Takayuki Kanaseki, Tomohide Tsukahara, Goro Kutomi, Tomohisa Furuhata, Koichi Hirata, Noriyuki Sato, Toru Mizuguchi, Ichiro Takemasa, Toshihiko Torigoe

Oncotarget ( Impact Journals LLC ) 8 ( 68 ) 112550 - 112564 2017年 [査読有り]

Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small subpopulation of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive. In this study, we aimed to determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N-Acetylgalactosaminide Alpha- 2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and increased the sphere-forming ability and resistance to a chemotherapeutic reagent. The opposite phenomena were observed by gene knockdown using siRNA. Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and activation of the pathway was cancelled by gene knockdown of galectin-3. The results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.

DOI

Liver Progenitors Isolated from Adult Healthy Mouse Liver Efficiently Differentiate to Functional Hepatocytes In Vitro and Repopulate Liver Tissue

Naoki Tanimizu, Norihisa Ichinohe, Masayuki Ishii, Junichi Kino, Toru Mizuguchi, Koichi Hirata, Toshihiro Mitaka

STEM CELLS ( WILEY-BLACKWELL ) 34 ( 12 ) 2889 - 2901 2016年12月 [査読有り]

It has been proposed that tissue stem cells supply multiple epithelial cells in mature tissues and organs. However, it is unclear whether tissue stem cells generally contribute to cellular turnover in normal healthy organs. Here, we show that liver progenitors distinct from bipotent liver stem/progenitor cells (LPCs) persistently exist in mouse livers and potentially contribute to tissue maintenance. We found that, in addition to LPCs isolated as EpCAM(+) cells, liver progenitors were enriched in CD45(-)TER119(-)CD31(-)EpCAM(-)ICAM-1(+) fraction isolated from late-fetal and postnatal livers. ICAM-1(+) liver progenitors were abundant by 4 weeks (4W) after birth. Although their number decreased with age, ICAM-1(+) liver progenitors existed in livers beyond that stage. We established liver progenitor clones derived from ICAM-1(+) cells between 1 and 20W and found that those clones efficiently differentiated into mature hepatocytes (MHs), which secreted albumin, eliminated ammonium ion, stored glycogen, and showed cytochrome P450 activity. Even after long-term culture, those clones kept potential to differentiate to MHs. When ICAM-1(+) clones were transplanted into nude mice after retrorsine treatment and 70% partial hepatectomy, donor cells were incorporated into liver plates and expressed hepatocyte nuclear factor 4 alpha, CCAAT/enhancer binding protein alpha, and carbamoylphosphate synthetase I. Moreover, after short-term treatment with oncostatin M, ICAM-1(+) clones could efficiently repopulate the recipient liver tissues. Our results indicate that liver progenitors that can efficiently differentiate to MHs exist in normal adult livers. Those liver progenitors could be an important source of new MHs for tissue maintenance and repair in vivo, and for regenerative medicine ex vivo.

DOI

Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy

Shigenori Ota, Miyuki Nishimura, Yuya Murakami, Naoko Kubo Birukawa, Akihiro Yoneda, Hiroki Nishita, Ryosuke Fujita, Yasushi Sato, Kenjiro Minomi, Keiko Kajiwara, Miyono Miyazaki, Maki Uchiumi, Shintaro Mikuni, Yasuaki Tamura, Toru Mizuguchi, Masafumi Imamura, Makoto Meguro, Yasutoshi Kimura, Koichi Hirata, Yoshiro Niitsu

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 11 ( 12 ) e0165747 2016年12月 [査読有り]

Background and objectives Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined. Methods Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection. Results In remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment. Conclusion aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.

DOI PubMed

Flap revascularization in patients following immediate reconstruction using an autologous free dermal fat graft for breast cancer: a report of two cases.

Hiroaki Shima, Goro Kutomi, Takuro Kyuno, Fukino Satomi, Satoko Uno, Hideki Maeda, Hidekazu Kameshima, Tosei Omura, Yasutoshi Kimura, Toru Mizuguchi, Koichi Hirata, Ichiro Takemasa

Surgical case reports 2 ( 1 ) 54 - 54 2016年12月 [国際誌]

It has been reported that use of the free dermal fat graft (FDFG) technique produces a good cosmetic outcome for breast cancer. An FDFG is harvested from the lower abdomen as a columnar-shaped specimen and implanted into the defect of the breast after a partial mastectomy as a volume replacement technique. In this report, two patients who underwent breast-conserving surgery with immediate reconstruction using an autologous FDFG are described in order to show the difference in status between one case with and one without blood flow in the graft. To assess the benefit of this technique using FDFGs, their cosmetic satisfaction was evaluated using a questionnaire, graft shrinkage was measured by CT, and blood flow was assessed using contrast-enhanced ultrasound (CEUS). Both patients scored 10 of 12 points on the questionnaire. After 2 years, shrinkage of the grafts was 21.6 and 25.2 %, respectively. Although one patient had no blood flow in the center of the graft, the other had blood flow from the pectoralis major muscle to the center of the graft. While satisfaction and graft shrinkage were similar in the two patients, one case showed blood flow and had a somewhat softer graft than the other. The graft status was maintained with a good cosmetic outcome for 3 years after breast-conserving surgery with immediate reconstruction using an autologous FDFG, despite mild shrinkage and hardness of the graft. It is notable that blood flow was observed into the graft on CEUS, and more distinct perfusion was seen in the softer graft case after more than 3 years.

DOI PubMed

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy.

Rena Morita, Yoshihiko Hirohashi, Toshihiko Torigoe, Satoko Ito-Inoda, Akari Takahashi, Tasuku Mariya, Hiroko Asanuma, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Terufumi Kubo, Goro Kutomi, Toru Mizuguchi, Takeshi Terui, Kunihiko Ishitani, Satoshi Hashino, Toru Kondo, Nozomi Minagawa, Norihiko Takahashi, Akinobu Taketomi, Satoru Todo, Masahiro Asaka, Noriyuki Sato

Clinical cancer research : an official journal of the American Association for Cancer Research 22 ( 13 ) 3298 - 309 2016年07月 [国際誌]

PURPOSE: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy. EXPERIMENTAL DESIGN: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model. RESULTS: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model. CONCLUSIONS: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR.

DOI PubMed

Intrahepatic Bile Ducts Are Developed Through Formation of Homogeneous Continuous Luminal Network and Its Dynamic Rearrangement in Mice

Naoki Tanimizu, Kota Kaneko, Tohru Itoh, Norihisa Ichinohe, Masayuki Ishii, Toru Mizuguchi, Koichi Hirata, Atsushi Miyajima, Toshihiro Mitaka

HEPATOLOGY ( WILEY-BLACKWELL ) 64 ( 1 ) 175 - 188 2016年07月 [査読有り]

The intrahepatic bile duct (IHBD) is a highly organized tubular structure consisting of cholangiocytes, biliary epithelial cells, which drains bile produced by hepatocytes into the duodenum. Although several models have been proposed, it remains unclear how the three-dimensional (3D) IHBD network develops during liver organogenesis. Using 3D imaging techniques, we demonstrate that the continuous luminal network of IHBDs is established by 1 week after birth. Beyond this stage, the IHBD network consists of large ducts running along portal veins (PVs) and small ductules forming a mesh-like network around PVs. By analyzing embryonic and neonatal livers, we found that newly differentiated cholangiocytes progressively form a continuous and homogeneous luminal network. Elongation of this continuous network toward the liver periphery was attenuated by a potent Notch-signaling inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester. Subsequent to this first step, the fine homogenous network is reorganized into the mature hierarchical network consisting of large ducts and small ductules. Between E17 and E18, when the homogenous network is radically reorganized into the mature hierarchical network, bile canaliculi rapidly extend and bile flow into IHBDs may increase. When formation of bile canaliculi was blocked between E16 and E18 by a multidrug resistance protein 2 inhibitor (benzbromarone), the structural rearrangement of IHBDs was significantly suppressed. Conclusion: Establishment of the mature IHBD network consists of two sequential events: (1) formation of the continuous luminal network regulated by the Notch-signaling pathway and (2) dynamic rearrangement of the homogeneous network into the hierarchical network induced by increased bile flow resulting from the establishment of hepatobiliary connections.

DOI PubMed

Pancreatic regeneration: basic research and gene regulation

Kenji Okita, Toru Mizuguchi, Ota Shigenori, Masayuki Ishii, Toshihiko Nishidate, Tomomi Ueki, Makoto Meguro, Yasutoshi Kimura, Naoki Tanimizu, Norihisa Ichinohe, Toshihiko Torigoe, Takashi Kojima, Toshihiro Mitaka, Noriyuki Sato, Norimasa Sawada, Koichi Hirata

SURGERY TODAY ( SPRINGER ) 46 ( 6 ) 633 - 640 2016年06月 [査読有り]

Pancreatic regeneration (PR) is an interesting phenomenon that could provide clues as to how the control of diabetes mellitus might be achieved. Due to the different regenerative abilities of the pancreas and liver, the molecular mechanism responsible for PR is largely unknown. In this review, we describe five representative murine models of PR and thirteen humoral mitogens that stimulate beta-cell proliferation. We also describe pancreatic ontogenesis, including the molecular transcriptional differences between alpha-cells and beta-cells. Furthermore, we review 14 murine models which carry defects in genes related to key transcription factors for pancreatic ontogenesis to gain further insight into pancreatic development.

DOI PubMed

Multiple hepatocellular adenomas: A case report

Fumito Tamura, Yutaka Kawano, Koji Miyanishi, Tomohiro Kubo, Yusuke Kamihara, Yutaka Okagawa, Kazuma Ishikawa, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Masaki Kawamoto, Makoto Meguro, Toru Mizuguchi, Ziro Ogino, Tadashi Hasegawa, Norihide Yoneda, Motoko Sasaki, Junji Kato

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 56 ( 11 ) 584 - 595 2015年12月

We report a rare case of multiple hepatocellular adenomas difficulty in ruling out well-differentiated hepatocellular carcinomas prior to resection. A 40s female was admitted to the hospital for examination of multiple liver tumors. CT and Gd-EOB-MRI showed that tumors were located in segment 2 and 5. We conducted a percutaneous tumor biopsy and tumor showed low atypical cells containing fat deposit. As the possibility of multiple hepatocellular carcinomas could not be denied, partial hepatectomy and RFA were done. All resected tumors showed a decreased expression of the liver fatty acid binding protein (L-FABP), and were finally diagnosed as multiple HNF1α-inactivated type hepatocellular adenomas Multiple hepatocellular adenomas are rare tumors, so we report this case with review of the literatures.

DOI

Surgical and oncological impact of main pancreatic duct spread in invasive ductal adenocarcinoma: A clinicopathological study of 184 resected cases

Masayuki Ishii, Yasutoshi Kimura, Shintaro Sugita, Masafumi Imamura, Tatsuya Ito, Takayuki Nobuoka, Makoto Meguro, Tadashi Hasegawa, Toru Mizuguchi, Koichi Hirata

PANCREATOLOGY ( KARGER ) 15 ( 6 ) 681 - 687 2015年11月 [査読有り]

Background/Objectives: This study examined main pancreatic ductal spread in invasive ductal adenocarcinoma (IDC) of the pancreas. Methods: Data from IDC patients who underwent radical surgery from 1990 to 2013 in our hospital were examined retrospectively. Incidence of intraductal spread of pancreatic cancer (IS), distance from the tumor edge, direction of IS and clinicopathological factors associated with the presence of IS were retrospectively examined with data from IDC patients who underwent radical surgery. Results: Among 260 IDC patients who underwent surgery, 184 eligible cases, IS was identified in 42 patients (22.8%) and mean length of IS was 18.7 +/- 21.6 mm. Mean distances on the ampullary and distal sides of IS were 11.1 mm and 11.6 mm. IS was significantly more frequent in localized tumors (UICC T1-2 vs. 3-4, p = 0.007), with tumor diameter <= 2 cm (p = 0.034) and in cases with scarce microscopic perineural invasion (p = 0.047). Among patients who underwent pancreaticoduodenectomy and distal pancreatectomy, IS presence (11.6 vs. 21.8%), mean distance to the contralateral side (11.4 vs. 11.6 mm), and IS >= 2 cm (3.3 vs. 4.7%) showed no significant differences. Overall survival did not differ significantly between IS-positive and -negative patients in the full analysis set or propensity score-matched patients (42 matched pairs). Conclusions: In setting resectional margins at 2 cm, a small proportion of cases (3.8%) showed positive surgical margins. Localized tumor (UICC: T1-2, or <2 cm in diameter) requires more care with surgical margins, warranting intraoperative frozen sections. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

DOI

Long-term and perioperative outcomes of laparoscopic versus open liver resection for colorectal liver metastases with propensity score matching: a multi-institutional Japanese study

Toru Beppu, Go Wakabayashi, Kiyoshi Hasegawa, Naoto Gotohda, Toru Mizuguchi, Yutaka Takahashi, Fumitoshi Hirokawa, Nobuhiko Taniai, Manabu Watanabe, Masato Katou, Hiroaki Nagano, Goro Honda, Hideo Baba, Norihiro Kokudo, Masaru Konishi, Koichi Hirata, Masakazu Yamamoto, Kazuhisa Uchiyama, Eiji Uchida, Shinya Kusachi, Keiichi Kubota, Masaki Mori, Keiichi Takahashi, Ken Kikuchi, Hiroaki Miyata, Takeshi Takahara, Masafumi Nakamura, Hironori Kaneko, Hiroki Yamaue, Masaru Miyazaki, Tadahiro Takada

JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES ( WILEY ) 22 ( 10 ) 711 - 720 2015年10月 [査読有り]

Background The aim of the present study was to clarify the surgical outcome and long-term prognosis of laparoscopic liver resection (LLR) compared with conventional open liver resection (OLR) in patients with colorectal liver metastases (CRLM). Methods A one-to-two propensity score matching (PSM) analysis was applied. Covariates (P<0.2) used for PSM estimation included preoperative levels of CEA and CA19-9; primary tumor differentiation; primary pathological lymph node metastasis; number, size, location, and distribution of CRLM; existence of extrahepatic metastasis; extent of hepatic resection; total bilirubin and prothrombin activity levels; and preoperative chemotherapy. Perioperative data and long-term survival were compared. Results From 2005 to 2010, 1,331 patients with hepatic resection for CRLM were enrolled. By PSM, 171 LLR and 342 OLR patients showed similar preoperative clinical characteristics. Median estimated blood loss (163 g vs 415 g, P<0.001) and median postoperative hospital stay (12 days vs 14 days; P<0.001) were significantly reduced in the LLR group. Morbidity and mortality were similar. Five-year rates of recurrence-free, overall, and disease-specific survival did not differ significantly. The R0 resection rate was similar. Conclusions In selected CRLM patients, LLR is strongly associated with lower blood loss and shorter hospital stay and has equivalent long-term survival comparable with OLR.

DOI PubMed

バイオマーカーをめぐるQ&A(Question 16) hERO1-Lα発現による乳癌予後予測は可能か?

九冨五郎, 久木田和晴, 里見蕗乃, 前田豪樹, 島宏彰, 水口徹, 平田公一

Surgery Frontier ( (株)メディカルレビュー社 ) 22 ( 3 ) 283 - 285 2015年09月

Clinical comparison of laparoscopic and open liver resection after propensity matching selection

Makoto Meguro, Toru Mizuguchi, Masaki Kawamoto, Shigenori Ota, Masayuki Ishii, Toshihiko Nishidate, Kenji Okita, Yasutoshi Kimura, Koichi Hirata

SURGERY ( MOSBY-ELSEVIER ) 158 ( 3 ) 573 - 587 2015年09月 [査読有り]

Background. This study aimed to compare the radicality for and clinical advantages of laparoscopic liver resection, which is increasingly used, and the corresponding open procedure by propensity score matching analysis. Methods. We analyzed 260 hepatocellular carcinoma patients who underwent initial liver resection at our department between January 2003 and June 2011, including 60 laparoscopic (the Lap group) and 200 open cases (the Open group). Propensity scores were calculated for each patient via the use of various clinicopathologic features as covariates, and patients' survival was compared. Results. The Lap group had more women and patients of advanced age (n = 60) than the Open group (n = 200). Tumor size (2.3 cm vs 3.5 cm median), multiple tumors (18.3% vs 41.0%), vascular invasion (15.0% vs 36.5%), poor differentiation status (11.2% vs 24.5%), intraoperative bleeding (110 mL vs 420 mL; median), and operative time (277 minutes vs 312 minutes; median) were significantly more favorable in the Lap group than in the Open group because of a selection bias of the patients (Lap vs Open). The postoperative recurrence-free and overall survival rates were greater in the Lap group than in the Open group; however, when 35 patients from each group were analyzed after propensity scare matching of clinicopathologic characteristics of the patients, intraoperative bleeding was lesser in the Lap group. The recurrence-free survival rates at 1, 3, and 5 years were 75.0%, 43.8%, and 43.8%, respectively, in the Lap group and 73.6%, 49.3%, and 37.2%, respectively, in the Open group, which indicated no significant differences (P = .954). Similarly, the overall survival rates at 1, 3, and 5 years were 93.9%, 82.1%, and 82.1%, respectively, in the Lap group and 94.3%, 85.2%, and 61.8%, respectively, in the Open group, indicating no significant differences between the 2 groups (P = .672). Conclusion. Our results indicate that laparoscopic liver resection is comparable with the corresponding open procedure in clinical safety and prognostic efficacy.

DOI

Effects of antecolic versus retrocolic reconstruction for gastro/duodenojejunostomy on delayed gastric emptying after pancreatoduodenectomy: A systematic review and meta-analysis

Masafumi Imamura, Yasutoshi Kimura, Tatsuya Ito, Takuro Kyuno, Takayuki Nobuoka, Toru Mizuguchi, Koichi Hirata

Journal of Surgical Research ( Academic Press Inc. ) 200 ( 1 ) 147 - 157 2015年05月

Background Delayed gastric emptying (DGE) is a relatively common complication after pancreatoduodenectomy (PD). The aim of this study was to determine whether DGE is affected by antecolic or retrocolic reconstruction for gastro/duodenojejunostomy after PD. Methods A literature search was performed of the MEDLINE (PubMed), Ovid SP, ISI Web of Knowledge, EMBASE, and Cochrane databases to identify randomized controlled trials (RCTs) and clinical observational studies related to this topic from January 1995 to November 2014. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for categorical outcomes, and mean differences (MD) using fixed-effect and random-effects models were calculated for the meta-analysis. Results Fourteen studies including 1969 patients met the inclusion criteria. Six studies were RCTs, and eight studies were clinical observational studies. DGE was less common in the antecolic reconstruction group than in the retrocolic reconstruction group (OR = 0.24 [0.12-0.48], P < 0.0001). Postoperative days to start solid foods (MD = -3.67 d [-5.10 to -2.33], P < 0.00001) and length of hospital stay (MD = -2.90 d [-5.36 to -2.33], P < 0.00001) were also significantly in favor of the antecolic reconstruction group. There was no difference in the incidence of pancreatic fistula, intra-abdominal fluid collection or abscess, biliary fistula, or mortality. However, in the subgroup analyses, using the data of six RCTs or seven studies according to the International Study Group of Pancreatic Surgery definition, there was no significant difference in the incidence of DGE. Conclusions Antecolic reconstruction for gastro/duodenojejunostomy does not seem to offer an advantage over retrocolic reconstruction with respect to DGE after PD.

DOI PubMed

Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

Makoto Meguro, Toru Mizuguchi, Toshihiko Nishidate, Kenji Okita, Masayuki Ishii, Shigenori Ota, Tomomi Ueki, Emi Akizuki, Koichi Hirata

World Journal of Gastroenterology ( WJG Press ) 21 ( 16 ) 4933 - 4945 2015年04月

AIM: To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections. METHODS: A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classifed into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by logrank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis. RESULTS: The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST):64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant difference in tumor size, vascular invasion, volume of intraoperative blood loss, and surgical duration however, no significant difference was observed between the three groups in liver function parameters except for albumin levels. In the LL group, the HL group, and the HH group, the MDFST was 50.09 ± 5.90, 31.01 ± 7.21, and 14.81 ± 3.08 mo (log-rank test, P < 0.001), respectively, and the MOST was 79.45 ± 8.30, 58.82 ± 7.56, and 32.87 ± 6.31 mo (log-rank test, P < 0.001), respectively. CONCLUSION: In the HBV group, the prognosis was poor when either AFP or DCP levels were high. In the HCV group, the prognosis was good when either or both levels were low however, the prognosis was poor when both levels were high. High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups. The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.

DOI PubMed

Clinical feasibility of laparoscopic lateral pelvic lymph node dissection following total mesorectal excision for advanced rectal cancer

Tomohisa Furuhata, Kenji Okita, Toshihiko Nishidate, Tatsuya Ito, Hiroshi Yamaguchi, Tomomi Ueki, Emi Akizuki, Makoto Meguro, Tadashi Ogawa, Kazuharu Kukita, Yasutoshi Kimura, Toru Mizuguchi, Koichi Hirata

SURGERY TODAY ( SPRINGER ) 45 ( 3 ) 310 - 314 2015年03月 [査読有り]

Purpose To evaluate the technical feasibility, safety and oncological outcomes of laparoscopic lateral pelvic lymph node dissection in patients with advanced low rectal cancer. Methods Laparoscopic lateral pelvic lymph node dissection was performed in 18 patients from November 2009 to September 2012. The data regarding the patient demographics, surgical outcomes and short-term oncological outcomes were analyzed. Results In all 18 patients, the procedures were completed without conversion to open surgery. The mean length of the operation was 603.7 min (473-746 min). The mean number of harvested lateral pelvic lymph nodes was 16.9 (7-27), and five patients (27.8 %) had lymph node metastases. The postoperative mortality and morbidity rates were 0 and 16.7 %, respectively. Three patients developed Grade 2 urinary retention. No local recurrence had developed after a mean follow-up period of 23.6 months. Conclusion Laparoscopic lateral pelvic lymph node dissection is technically feasible, safe and oncologically acceptable within the limitations of the short-term follow-up period.

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An immunohistochemical marker panel including claudin-18, maspin, and p53 improves diagnostic accuracy of bile duct neoplasms in surgical and presurgical biopsy specimens.

Yoshiko Keira, Akira Takasawa, Masaki Murata, Masanori Nojima, Kumi Takasawa, Jiro Ogino, Yukimura Higashiura, Ayaka Sasaki, Yasutoshi Kimura, Toru Mizuguchi, Satoshi Tanaka, Koichi Hirata, Norimasa Sawada, Tadashi Hasegawa

Virchows Archiv : an international journal of pathology 466 ( 3 ) 265 - 77 2015年03月 [国際誌]

Biliary tract cancers have an extremely poor outcome, and specific diagnostic markers and effective treatments are needed urgently. In this study, we assessed the capacity of panel of immunohistochemical markers including claudin-18, maspin, and p53 to distinguish biliary tract carcinoma and biliary intraepithelial neoplasia (BilIN) from non-neoplastic epithelium. We performed a retrospective study of 66 biliary tract cancer specimens and 63 specimens with non-neoplastic lesions. Of the surgical specimens, 96.7 % with adenocarcinoma/BilIN were detected as neoplastic, and all 63 specimens histologically diagnosed as non-neoplastic lesion were detected as non-neoplastic with high sensitivity (91.1 %) and specificity (100 %). Of presurgical endobiliary forceps biopsy specimens, all with adenocarcinoma/BilIN and only 1 of the 19 with a non-neoplastic lesion were distinguished as neoplastic with high sensitivity (100 %) and specificity (94.7 %). Moreover, this panel provided good separation of neoplasm from malignancy-undetermined atypical epithelium (18/21, 85.7 %). This panel achieves a more reliable distinction of biliary tract cancers and BilINs from non-neoplastic epithelia in both surgical and biopsy specimens than immunohistochemical analysis with single antibodies and is useful in supporting a diagnosis of adenocarcinoma and BilIN.

DOI PubMed

A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer

Yasushi Sato, Hiroyuki Ohnuma, Masahiro Hirakawa, Minoru Takahashi, Takahiro Osuga, Yutaka Okagawa, Kazuyuki Murase, Kohichi Takada, Yutaka Kawano, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Kenji Okita, Toru Mizuguchi, Tomohisa Furuhata, Koichi Hirata, Junji Kato

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 75 ( 3 ) 587 - 594 2015年03月 [査読有り]

The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC). Patients received oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2 to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD). Twelve patients received a median of 6.5 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m(2). The most common grade a parts per thousand yen3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively. XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.

DOI

New technique of extracorporeal hepatic inflow control for pure laparoscopic liver resection

Toru Mizuguchi, Masaki Kawamoto, Yukio Nakamura, Makoto Meguro, Thomas T. Hui, Koichi Hirata

Surgical Laparoscopy, Endoscopy and Percutaneous Techniques ( Lippincott Williams and Wilkins ) 25 ( 1 ) e16 - e20 2015年02月

We have developed a new technique of the Pringle maneuver by clamping outside the abdominal wall for pure laparoscopic liver resection (pure Lap). Our technique successfully controls bleeding and enables pure Lap to be completed without any events, even for a large tumor. Between 2008 and 2010, we compared consecutive patients who received pure Lap with (n=11) and without (n=7) this Pringle maneuver. Although tumor size in the Pringle group was significantly larger than in the no-Pringle group (3.35±1.64 vs. 1.11±0.29 cm, respectively), intraoperative bleeding was not significantly different (165.5±188.5 vs. 177.9±364.4 mL, respectively). In contrast, operation time in the Pringle group was significantly longer than in the no-Pringle group (343.1±99.5 vs. 199.6±63.2 min, respectively). Pure Lap for large tumors is feasible when employing a new Pringle maneuver outside the abdominal wall.

DOI PubMed

Prognostic value of HLA class I expression in patients with colorectal cancer

Yuji Iwayama, Tetsuhiro Tsuruma, Toru Mizuguchi, Tomohisa Furuhata, Nobuhiko Toyota, Masayuki Matsumura, Toshihiko Torigoe, Noriyuki Sato, Koichi Hirata

WORLD JOURNAL OF SURGICAL ONCOLOGY ( BIOMED CENTRAL LTD ) 13 2015年02月 [査読有り]

Background: Prognostic factors are useful for determination of the therapeutic strategy and follow-up examination after curative operation in cancer treatment. The immunological state of the host can influence the prognosis for cancer patients as well as the features of the cancer. Human lymphocyte antigen (HLA) class I molecules have a central role in the anti-cancer immune system. Therefore, we focused on the HLA class I expression level in cancer cells to investigate its prognostic value in patients with colorectal cancer. Methods: We reviewed the clinical pathology archives of 97 consecutive patients with stage II colorectal cancer who underwent curative operation at the Sapporo Medical University, Japan, from February 1994 to January 2005. Fifty-six high-risk patients had adjuvant chemotherapy. The cancer cell membrane immunoreactivity level for HLA class I expressed by EMR8-5 was classified into three categories (positive, dull, and negative). In this study, the cases were divided into two groups: "positive" and "dull/negative". HLA class I expression level and clinicopathological parameters were evaluated with the Pearson chi(2) test. Survival analysis was assessed by the Kaplan-Meier methods, and the differences between survival curves were analyzed using the log-rank test. Results: Immunohistochemical study of HLA class I revealed the following. There were 51 cases that were positive, 40 were dull, and six negative. The HLA class I expression level had no significant correlation with other clinicopathological parameters, except for gender. Univariate and multivariate analyses related to disease-free survival (DFS) revealed that tumor location, HLA expression level, and venous invasion were significant independent prognostic factors (P < 0.05). The 5-year DFS rates in HLA class I positive group and in the dull/negative group were 89% and 70%, respectively. For high-risk patients with adjuvant chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 84% and 68%, respectively. For low-risk patients without the chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 100% and 71%, respectively. Conclusions: Our study concluded that the HLA class I expression level might be a very sensitive prognostic factor in colorectal cancer patients with stage II disease.

DOI

Remnant Pancreas Reconstruction with Duct-To-Duct Anastomosis after Middle Pancreatectomy: A Report of Two Cases

Masayuki Ishii, Yasutoshi Kimura, Masafumi Imamura, Daisuke Kyuno, Tomomi Ueki, Motonobu Uchiyama, Toru Mizuguchi, Mitsuhiro Mukaiya, Koichi Hirata

HEPATO-GASTROENTEROLOGY ( H G E UPDATE MEDICAL PUBLISHING S A ) 62 ( 137 ) 190 - 194 2015年01月 [査読有り]

Reconstruction of a remnant pancreas after middle pancreatectomy has generally been performed with. a pancreaticoenterostomy. We report here two cases in which physiological reconstructive procedures were performed. The reconstructive procedures included pancreatic duct-to-duct anastomosis and parenchymal sutures with absorbable monofilament interrupted stitches. A pancreatic tube was inserted for decompression at the anastomotic site in both cases. The patients comprised one with pancreatic metastasis from renal cell carcinoma and another with a non-malignant insulinoma. The tumors were located in the pancreatic body. Although an International Study Group on Pancreatic Fistula classification grade B-pancreatic fistula was observed in each patient, they both resolved with conservative therapy. The pancreatic duct at the anastomosis site was patent in both cases, and no atrophic changes developed in the remnant pancreas in either patient. These outcomes confirmed that, in selected cases, this reconstructive procedure is safe and feasible for physiological reconstruction without involvement of the digestive tract.

DOI

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