Details of a Researcher - MIZUGUCHI Tooru

Papers - MIZUGUCHI Tooru

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膵IPMCと胆管IPMNが並存した1例

永山稔, 木村康利, 今野愛, 信岡隆幸, 水口徹, 古畑智久, 平田公一

北海道外科雑誌 ( 北海道外科学会 ) 53 ( 1 ) 96 - 96 2008.06

術前に腫瘤を指摘しえなかった膵癌の1例

今野愛, 木村康利, 永山稔, 信岡隆幸, 古畑智久, 水口徹, 石渡裕俊, 林毅, 新津洋司郎, 平田公一

北海道外科雑誌 ( 北海道外科学会 ) 53 ( 1 ) 94 - 94 2008.06

【膵切除術の術式選択と手術手技】膵頭部浸潤性膵管癌に対する外科治療

永山稔, 木村康利, 今野愛, 信岡隆幸, 水口徹, 古畑智久, 平田公一

消化器外科 ( (株)へるす出版 ) 31 ( 7 ) 1123 - 1131 2008.06

腹腔鏡下脾臓摘出術の有用性開腹術との比較による臨床的検討

永山稔, 木村康利, 今野愛, 信岡隆幸, 西舘敏彦, 水口徹, 古畑智久, 平田公一

日本臨床外科学会雑誌 ( 日本臨床外科学会 ) 69 ( 3 ) 709 - 709 2008.03

腫瘍性病変疑診例に対する腹腔鏡下膵切除

今野愛, 木村康利, 永山稔, 信岡隆幸, 今村将史, 秋月恵美, 水口徹, 古畑智久, 平田公一

日本臨床外科学会雑誌 ( 日本臨床外科学会 ) 69 ( 3 ) 714 - 714 2008.03

Short- and midterm outcomes of laparoscopy-assisted colectomy for colon and rectosigmoid cancer

Toshihiko Nishidate, Tomohisa Furuhata, Kenji Okita, Makoto Meguro, Gentaro Ishiyama, Takayuki Nobuoka, Koji Yamaguchi, Yasutoshi Kimura, Toru Mizuguchi, Fumitake Hata, Koichi Hirata

Tumor Research 43 31 - 37 2008

Background: Laparoscopy-assisted colectomy (LAC) has gained acceptance for the treatment of colon cancer. Objective: To evaluate the use and outcomes of LAC. Patients: Patients who underwent LAC (n = 176) for colon and rectosigmoid cancer (2001-2008). Results: There were 97 men (55.1%) and 79 women(44.9%), whose median age was 67.5 years (range, 33-99 years). The median operating time for patients who underwent LAC was 216 minutes (range, 70-440). The median blood loss was 60 ml (range 10-610 ml). Intra- and postoperative complications occurred in 3 (1.7%) and 16 patients (9.1%) respectively. The morbidity rate of patient was 0%. The overall survival rates for 3 years were 100.0%, 97.5%, 95.9%, 90.1% and 77.9% for stages 0 I, II, IIIa and IIIb, respectively. The relapse-free survival rates for 3 years were 100.0%, 100.0% 90.1%, 65.7% and 62.3% for stages 0, I, II, IIIa and IIIb, respectively. Conclusion: This study confirmed the favorable short- and midterm operative results in patients who underwent LAC.

Efficient transformation of small hepatocytes into insulin-expressing cells by forced expression of Pdx1.

Kawasaki H, Mizuguchi T, Oshima H, Nobuoka T, Shibata T, Kaji S, Kokai Y, Katsuramaki T, Mitaka T, Hirata K

Journal of hepato-biliary-pancreatic surgery ( 4 ) 15 403 - 409 2008 [Refereed]

DOI PubMed

Proliferation of Hepatocyte Progenitor Cells Isolated From Adult Human Livers in Serum-Free Medium

Kazunori Sasaki, Rtnko Kon, Toru Mizuguchi, Qijie Chen, Hidekazu Ooe, Hideki Oshima, Koichi Hirata, Toshihiro Mitaka

CELL TRANSPLANTATION ( COGNIZANT COMMUNICATION CORP ) 17 ( 10-11 ) 1221 - 1230 2008 [Refereed]

Rat small hepatocytes (SHs) are committed progenitor cells that can differentiate into mature hepatocytes and can selectively proliferate in serum-free medium when they are cultured on hyaluronic acid (HA)-coated dishes. In this study we examined the separation of human SHs from adult human livers. We obtained liver tissues from the resected liver of 16 patients who underwent hepatic resections. Extracted liver specimens were clearly separate from the tumor regions with sufficient margins. Hepatic cells were isolated using the modified method of two-step collagenase perfusion. A low-speed centrifugation was performed and cells in the supernatant were finally cultured on HA-coated dishes in serum-free DMEM/F12 medium including nicotinamide, EGF, and HGF. Small-sized hepatocytes selectively proliferated to form colonies and many colonies continued growing for more than 3 weeks. The average number of cells in a colony was 38.6 +/- 18.0, 79.0 +/- 54.0, and 101.5 +/- 115.7 at day 7, 14, and 21, respectively. About 0.04% of plated cells could form an SH colony. Immunocytochemistry showed that the cells forming a colony were positive for albumin, transferrin, keratin 8, and CD44. The results of RT-PCR showed that colony-forming cells expressed albumin, transferrin, alpha(1)-antitrypsin, fibrinogen, glutamine synthetase, many cytochrome P450s, and liver-enriched transcription factors (HNF3 alpha, HNF4 alpha, C/EBP alpha, and C/EBP beta. Furthermore, the cells expressed not only the genes of hepatic differentiated functions but also those of both hepatic stein cell marker (Thy1.1, EpCAM, AFP) and SH marker (CD44, D6.1A, BRI3). Albumin secretion into culture medium was also observed. Our results demonstrate the existence of hepatocyte progenitor cells in human adult livers, and the cells can grow in a serum-free medium on HA-coated dishes. Human SHs may be a useful source for cell transplantation as well as pharmaceutical and toxicological investigations.

PubMed

In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone-producing cells.

Hiroyuki Kawasaki, Toru Mizuguchi, Yamato Kikkawa, Hideki Oshima, Yasushi Sasaki, Takashi Tokino, Yasuo Kokai, Jun-Ichi Miyazaki, Tadashi Katsuramaki, Toshihiro Mitaka, Koichi Hirata

Journal of hepato-biliary-pancreatic surgery 15 ( 3 ) 310 - 7 2008 [Refereed] [Domestic journal]

BACKGROUND/PURPOSE: Pancreatic and duodenal homeobox factor 1 (Pdx-1) plays an important role in initiating differentiation toward pancreatic endocrine cells. The transdifferentiation or transformation of hepatocytes into pancreatic endocrine cells could be feasible, due to their similar cellular origins. Our goal in this study was to see if small hepatocytes (SHs) could give rise to pancreatic endocrine cells via exogenous Pdx-1 gene expression. METHODS: SHs were cultured for 10 days before adenovirus (Adt)-mediated Pdx-1 gene transfection. We performed western blot analysis for pancreatic transcription factors in the nuclei and reverse-transcription polymerase chain reaction (RT-PCR) for the gene expression of pancreatic endocrine hormones. Confocal laser microscanning analysis was used to observe the transformation of SHs. RESULTS: Pancreatic transcription factors such as Pdx-1, Ngn3, NeuroD, Nkx2.2, and Pax6 were induced after Adt-Pdx-1 gene transfection. The mRNA expression of pancreatic endocrine hormones (insulin, glucagon, and somatostatin) was induced after the gene transfection. Pdx-1 was expressed in the nucleus, where the cells were positive for one or more of the hormones and cytokeratin (CK) 8. Some cells were positive for multiple hormones. The insulin level increased while the glucagon level decreased after the glucose loading test, depending on the glucose concentration. CONCLUSIONS: SHs are transformed into functional pancreatic endocrine cells after Pdx-1 gene transfection.

DOI PubMed

Surgical treatment for gallbladder carcinoma with subserosal invasion

NOBUOKA Takayuki, KIMURA Yasutoshi, OHONO Keisuke, NISHIDATE Toshihiko, AKIZUKI Emi, MIZUGUCHI Toru, MUKAIYA Mitsuhiro, HIRATA Koichi

Tando ( Japan Biliary Association ) 21 ( 5 ) 630 - 636 2007.12

We investigated clinicopathological factors and prognosis for appropriate operation for 44 patients who received resections for gallbladder carcinoma with subserosal invasion. Their 5-year survival rate was 50.2%. There was a significant difference in the survival rate between the patients with and without hepatectomy, whereas there was no survival advantage for the anatomical liver resection or partial hepatectomy group cornpared with the extended cholecystectomy group. However, the 3-year survival rate of patients who underwent pancreaticoduodenectomy was 83.3%; the outcome after pancreaticoduodenectomy was comparable to that after resection of the bile duct. A significant difference in the survival rate was observed between lympahadectomy with D2 and D0/1. In particular, the tendency was remarkable in the gallbladder neck and cystic duct carcinoma. The significance of anatomical liver resection, pancreaticoduodenectomy, and resection of the bile duct was indistinct. The presence of lymph node metastasis was an independent prognostic factor by multivariate analyses. These results suggest that radical resection with hepatectomy and lympahadectomy with D2 is the appropriate procedure for gallbladder carcinoma with subserosal invasion.

DOI CiNii

腹腔鏡下脾臓摘出術の有用性開腹術との比較による臨床的検討

永山稔, 木村康利, 今野愛, 信岡隆幸, 水口徹, 古畑智久, 平田公一

北海道外科雑誌 ( 北海道外科学会 ) 52 ( 2 ) 144 - 147 2007.12

教室で施行した脾臓摘出術症例を、鏡視下手術(LS群)と開腹手術(OS群)にわけ、術後回復過程での鏡視下手術の有用性について検討した。1994年8月から2007年8月までに、教室で施行した脾臓摘出術症例27例を対象とした。LS群は21例(うち、用手補助腹腔鏡下手術3例)、OS群は6例であった。疾患は、LS群では特発性血小板減少性紫斑病、肝硬変に伴う脾機能亢進症、脾腫瘍が(それぞれ6例)、OS群では特発性血小板減少性紫斑病が3例で最も多かった。手術因子として、平均手術時間と出血量において両群間に差はなかった。一方、周術期因子として頓用鎮痛薬使用期間(LS群:1.9日、OS群:6.4日)と術後在院期間(LS群:9.2日、OS群:17.5日)で有意にLS群が短かった(p<0.05)。腹腔鏡下脾臓摘出術は、低侵襲かつ安全に施行されており、今後ますますその需要が増えると考えられた。(著者抄録)

New strategy for the antifibrotic therapy with oral administration of FR260330 (a selective inducible nitric oxide synthase inhibitor) in rat experimental liver cirrhosis

Hitoshi Kikuchi, Tadashi Katsuramaki, Kazuma Kukita, Sonofu Taketani, Makoto Meguro, Minoru Nagayama, Masato Isobe, Toru Mizuguchi, Koichi Hirata

Wound Repair and Regeneration 15 ( 6 ) 881 - 888 2007.11

Inducible nitric oxide synthase (iNOS) activity is significantly elevated in viral hepatitis, alcoholic cirrhosis, and cholestasis. However, there are few reports on the relationship between iNOS and cirrhosis. Here, we investigated the effects of a new iNOS inhibitor that has been developed for oral administration in an experimental rat liver cirrhosis model. A cirrhotic rat model was developed by long-term administration of thioacetamide injections. FR260330 is a new, rationally designed, selective iNOS inhibitor that can be administered orally. After 12 weeks of treatment with FR260330, the rats showed inhibition of progressions of cirrhosis, ascites, and splenomegaly as well as a significant reduction in the proportions of connective tissue in the liver. The expression of nitrotyrosine, which indicates the existence of peroxynitrite and nuclear factor-κB activation, was remarkably decreased in the FR260330 treatment group. In addition, immunohistochemical and Western blot analyses showed that the expression of transforming growth factor-β1 was remarkably decreased in this group. The present study demonstrates that FR260330 reduces liver fibrosis by the inhibition of transforming growth factor-β1 and retards the development of cirrhosis. This oral iNOS inhibitor will be a new strategy for the treatment of cirrhosis. © 2007 by the Wound Healing Society.

DOI PubMed

Current status of surgery for pancreatic cancer.

Hirata Koichi, Egawa Shinichi, Kimura Yasutoshi, Nobuoka Takayuki, Oshima Hidenori, Katsuramaki Tadashi, Mizuguchi Toru, Furuhata Tomohisa

Dig Surg 24 ( 2 ) 137 - 147 2007.04 [Refereed]

DOI PubMed

Assessment of nutritional status and prediction of postoperative liver function from serum apolioprotein A-1 levels with hepatectomy

Tadashi Katsuramaki, Toru Mizuguchi, Masaki Kawamoto, Kouji Yamaguchi, Makoto Meguro, Minoru Nagayama, Takayuki Nobuoka, Yasutoshi Kimura, Tomohisa Furuhata, Koichi Hirata

WORLD JOURNAL OF SURGERY ( SPRINGER ) 30 ( 10 ) 1886 - 1891 2006.10 [Refereed]

Background: We investigated the usefulness-of apolipoprotein A-1 (apoA) as an indicator of nutritional status, and the correlation of the preoperative apoA level with changes in postoperative liver function following hepatectomy. Methods: One hundred patients underwent hepatectomy. Serum levels of apoA, prealbumin (prealb), retinol-binding protein (RBP), lectin-cholesterol acyltransferase (LCAT), hyarulonate (HA), indocyanine green dye retention at 15 minutes (ICG), and the receptor index of Tc-GSA scintigraphy (LHL15) were measured at preoperation and on postoperative days (POD) 7 and 14. Partial resection was carried out in 62 cases, segmentectomy in nine cases, and bisegmentectomy in 29 cases. Co-existent liver conditions were normal liver (NL) in 43 cases, chronic hepatitis (CH) in 29 cases, and liver cirrhosis (LC), in 28 cases. Results: In most cases the serum apoA level had decreased on POD 7, and recovered on POD 14. There were no significant differences in the changes of apoA between the individual operative procedures. Although preoperative apoA had almost the same value in the NL, CH, and LC cases, apoA in LC cases on POD 114 was the lowest of all cases. The apoA level showed significant correlations with prealb, LCAT, and HA on POD 14. All cases were divided into two groups (group N: apoA over 91 mg/dl; group L: apoA under 90 mg/dl) based on the preoperative serum apoA level. On POD 14, the ICG, LHL15, and HA of group L were significantly deteriorated compared with those of group L. Conclusion: The serum level of apoA reflects the changes in hepatic protein synthetic ability after hepatectomy; therefore, it may be possible to estimate recovery of nutritional status after hepatectomy from serum apoA. Moreover, we can predict postoperative deterioration of liver function from the preoperative apoA level.

DOI

In situ graft-trimming method using polyester vascular prosthesis for inferior vena cava reconstruction after hepatectomy

Toru Mizuguchi, Tadashi Katsuramaki, Kiyofumi Morishita, Masaki Kawamoto, Takayuki Nobuoka, Masato Imamura, Yasutoshi Kimura, Koichi Hirata

Digestive Surgery 23 ( 1-2 ) 115 - 118 2006.08

Hepatectomy for secondary liver cancer that has invaded the inferior vena cava (IVC) can be the only way to achieve long-term survival. We describe a method for hepatectomy combined with partial IVC resection without venous bypass circulation and an in situ graft-trimming method to avoid graft size mismatch after reconstruction. We carried out left hepatectomy extended to segment 1 with partial IVC resection first. During resection and reconstruction of the IVC, it was clamped below the right hepatic vein and above the inferior right hepatic vein to maintain systemic circulation. The graft was trimmed in situ, after a half running suture of the graft was finished to ensure the correct size. Preservation of both inferior right hepatic vein and right hepatic vein helps to maintain systemic circulation during reconstruction of the IVC. The in situ graft-trimming method is an easy and safe method to ensure the correct graft size after IVC reconstruction. Copyright © 2006 S. Karger AG.

DOI PubMed

Assessment of liver fibrosis by a noninvasive method of transient elastography and biochemical markers

Masaki Kawamoto, Toru Mizuguchi, Tadashi Katsuramaki, Minoru Nagayama, Hideki Oshima, Hiroyuki Kawasaki, Takayuki Nobuoka, Tasutoshi Kimura, Koichi Hirata

World Journal of Gastroenterology ( Baishideng Publishing Group Co ) 12 ( 27 ) 4325 - 4330 2006.07

Aim: To assess the correlation between the fibrotic area (FA) as calculated by a digital image analysis (DIA), and to compare the diagnostic accuracy of FibroScan to the other existing Liver fibrosis (LF) markers using the receiver operating curve analysis. Methods: We recruited 30 patients who underwent a liver resection for three different etiologies including normal liver, hepatitis B, and hepatitis C. Liver stiffness was measured by using a FibroScan. The FA was then calculated by DIA to evaluate LF in order to avoid any sampling bias. Results: The FA negatively correlated with Prothrombin time (PT), platelet count, lecithin-cholesterol acyltransferase (LCAT), and pre-albumin (ALB). On the other hand, the findings of FibroScan correlated with similar markers. The FA positively correlated with FibroScan, serum hyaluronate level, and type IV collagen level, and aspartate transaminase to platelet ratio index (APRI). The area under the receiver operating curve for FibroScan was higher than that for the other markers, even though the statistical significance was minimal. Conclusion: Our findings suggest that FibroScan can initially be used to assess LF as an alternative to a liver biopsy (LB) and serum diagnosis, because it is a safe method with comparable diagnostic accuracy regarding the existing LF markers. © 2006 The WJG Press. All rights reserved.

DOI PubMed

Serum lipid and lipoprotein alterations represent recovery of liver function after hepatectomy

M Kawamoto, T Mizuguchi, M Nagayama, T Nobuoka, H Kawasaki, T Sato, K Koito, S Parker, T Katsuramaki, K Hirata

LIVER INTERNATIONAL ( BLACKWELL PUBLISHING ) 26 ( 2 ) 203 - 210 2006.03 [Refereed]

Background: The assessment of liver function during human liver regeneration is necessary to prevent unexpected liver failure and to prepare for further treatment. We selected patients prospectively and measured serum lipid and lipoprotein levels to identify which lipids and lipoproteins could represent recovery of liver function in human liver regeneration. Methods: Thirty selected patients who underwent hepatectomy were divided into three groups depending on the serum hyaluronate (HA) level and the type of liver resection. Results: We found three patterns of lipid and lipoprotein alterations after hepatectomy. Among the lipids and lipoproteins examined, the serum beta-lipoprotein and low-density lipoprotein (LDL) levels were significantly different among the groups at 7 days after hepatectomy. The alteration of the apolipoprotein (Apo) B level was similar to that of LDL. The LDL level was correlated with both beta-lipoprotein and Apo B before hepatectomy (r=0.653 and 0.894, respectively) and at 7 days after hepatectomy (r=0.841 and 0.943, respectively). Conclusion: Serum HA before hepatectomy can reflect postoperative liver function depending on the type of liver resection. Recovery of the beta-lipoprotein and LDL levels can reflect the recovery of liver function in human liver regeneration within the early period in association with the Apo B level.

DOI

Liver repopulation and long-term function of rat small hepatocyte transplantation as an alternative cell source for hepatocyte transplantation

C Shibata, T Mizuguchi, Y Kikkawa, T Nobuoka, H Oshima, H Kawasaki, M Kawamoto, T Katsuramaki, T Mitaka, K Hirata

LIVER TRANSPLANTATION ( JOHN WILEY & SONS INC ) 12 ( 1 ) 78 - 87 2006.01 [Refereed]

Hepatocyte transplantation (HT) is an attractive therapeutic modality for liver disease as an alternative for liver organ transplantation. Primary fresh hepatocytes (FHs) are the exclusive cell source that has been used for clinical HT, However, the use of FHs is limited due to a shortage of donor cells. Small hepatocytes (SHs) are hepatic progenitor cells and can be isolated not only from rodents but also from humans. SHs can proliferate in vitro and express liver functions, although conventional hepatocytes lose them within a short period after culture. SH functions in vivo have never been studied. We therefore investigated HT using SHs to evaluate cell engraftment and function compared to HT using FHs. The donor cell number in the SH group was smaller than that in the FH group at HT. The cell engraftment in the SH group was smaller in the liver and larger in the spleen than in the FH group. The cell engraftment in the liver increased after HT; however, that in the spleen decreased after HT in both groups. HT using SHs supported the serum albumin level in the NAR experiment as well as that using FH, and albumin mRNA was detectable in the recipients' tissues at 12 weeks after HT. In conclusion, HT using SHs showed hepatic repopulation similar to that using FHs. This suggests that both SHs and FHs can repopulate the liver as if they were hepatic stem cells. In addition, HT using SHs supported liver functions such as albumin correction at the same level as that using FHs. These observations strongly support the idea that SHs could be an alternative to primary FHs as a novel cell source for future HT.

DOI PubMed

Successful management of locally advanced hilar cholangiocarcinoma : Surgical procedure for extended left hepatic lobectomy coupled by resection/ reconstruction of the right hepatic artery

Akizuki Shindo Emi, Kimura Yasutoshi, Mukaiya Mitsuhiro, Honnma Toshio, Mizuguchi Toru, Furuhata Tomohisa, Koito Kazumitsu, Katsuramaki Tadashi, Hirata Koichi

Tumor Research ( Sapporo Medical University ) 41 77 - 81 2006

Recently, the methods for hepatic lobectomy, which require highly qualified and experienced surgeons and include difficult post-operative management, have improved markedly, and, moreover, there are very few patient deaths resulting from hepatic artery reconstruction. Now, as an overall trend, the focus of discussion has shifted to whether there is any positive value in radical resection. A few reports have described success in such operations.Extended left hepatectomy with right hepatic artery resection in a case of advanced hilar cholangiocarcinoma with suspected right hepatic artery invasion is reported. The surgery absolutely required reconstruction of the hepatic artery. During the postoperative course, in which the patient was at high risk for complications, temporary bleeding was observed from a pseudo aneurysm in the anastomotic site. Fortunately, no severe problems were caused by transarterial embolization in the right hepatic artery. The patient completed the planned chemotherapy regimen and was discharged.

DOI CiNii

Portal blood flow regulates volume recovery of the rat liver after partial hepatectomy: Molecular evaluation

T. Nobuoka, T. Mizuguchi, H. Oshima, T. Shibata, Y. Kimura, T. Mitaka, T. Katsuramaki, K. Hirata

EUROPEAN SURGICAL RESEARCH ( KARGER ) 38 ( 6 ) 522 - 532 2006 [Refereed]

Background/Aim: Liver regeneration is a finely tuned process that is closely regulated by multiple cell cycle steps. Although the portal blood flow affects liver regeneration, the molecular mechanism by which the blood flow regulates gene expression and liver function is largely unknown. The aim of this study was to investigate the molecular effect of portal blood flow on hepatocyte proliferation and gene regulation during liver regeneration. Materials and Methods: We developed a simple surgical rat model to investigate the relation between portal blood flow and liver regeneration by partially ligating the portal trunk with 8-0 Proline sutures under microscopy to reduce the blood flow by 40%. We investigated recovery of liver volume, DNA synthesis, and gene expression associated with cell cycle regulators, comparing partially hepatectomized (PH) rats without (PH group; n = 30) and with partial portal ligation (PHPL group; n = 30) for 7 days after the operation. Results: The hepatic tissue blood flow and the recovery ratio between liver weight and body weight in the PHPL group were significantly lower than in the PH group after hepatectomy. The peak 5-bromo-2'-deoxyuridine labeling index in the PHPL group was delayed and weak compared with the PH group. The expression of CT-1 and cyclin D, E, and B mRNAs indicated that the liver regeneration in the PHPL group was delayed and weak. In addition, there was reciprocal expression of C/EBP alpha and C/EBP beta mRNAs, an observation supported by their nuclear protein levels. Furthermore, the cytochrome P-450 protein level in the PHPL group was higher than that in the PH group 1 day after hepatectomy. Conclusion: The portal blood flow regulates the activity of liver regeneration and the gene expression associated with cell cycle regulators, while the functions are maintained. Copyright (c) 2006 S. Karger AG, Basel.

DOI

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