研究者詳細 - 水口　徹

論文 - 水口　徹

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当科における肝切除術における手術創およびドレーン管理

久木田和晴, 水口徹, 川本雅樹, 目黒誠, 永山稔, 信岡隆幸, 木村康利, 古畑智久, 平田公一

北海道外科雑誌 ( 北海道外科学会 ) 54 ( 2 ) 159 - 159 2009年12月

当科における腹腔鏡(補助)下肝切除術の現状と標準化に向けて

目黒誠, 水口徹, 川本雅樹, 久木田和晴, 永山稔, 西舘敏彦, 沖田憲司, 信岡隆幸, 木村康利, 古畑智久, 平田公一

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 14 ( 7 ) 598 - 598 2009年12月

当科の肝切除術における創管理法の工夫と術後創感染の検討

目黒誠, 水口徹, 川本雅樹, 久木田和晴, 西舘敏彦, 沖田憲司, 永山稔, 信岡隆幸, 木村康利, 古畑智久, 平田公一

北海道外科雑誌 ( 北海道外科学会 ) 54 ( 2 ) 119 - 123 2009年12月

肝切除術の開腹創は良好な視野を得るために比較的大きく、体壁破壊による術後疼痛持続・残存や創感染機会が他の術創に比し高い。当科で施行してきたHCCに対する肝切除時の皮膚切開方法やドレーン管理法を前期群62例(2001年1月から2003年12月)(上腹部正中+八字切開、絹糸使用、ソフトプリーツドレーン留置)と後期群50例(2004年1月から2006年7月)(逆T字or逆L字切開、吸収糸使用、皮下にも閉鎖吸引式BLAKEドレーン(Johnson & Johnson,Co.,Ltd.)留置)に分けて検討し、肝切除後の創感染(漿液腫を含む)に与える影響について検討した。その結果、前期群で13例(11.6%)、後期群で5例(4.5%)、に創感染を生じたが有意差はなかった(p=0.116)ものの、後期群で頻度が半減した。全期間において、創感染群(18例)と非感染群(94例)に分けて単変量解析を施行したところ、肝予備能の低い症例で有意に創感染の頻度が高かった。多変量解析では、ICG15分値において有意差を認め[RR=1.084(1.009-1.165)、p=0.027]、ICG15分値が16.8%以上の症例でとくに創感染のリスクが高かった(感度66.7%、特異度74.5%)。肝切除術後の創感染発生予防には適切な閉鎖吸引式ドレーン管理と閉腹・閉創方法が重要であり、肝予備能が低い症例では、とくに有用であると思われた。(著者抄録)

Effects of a low-fat meal on the oral bioavailability of UFT and leucovorin in patients with colorectal cancer

Tomohisa Furuhata, Makoto Meguro, Toshihiko Nishidate, Kenji Okita, Gentarou Ishiyama, Yuuji Iwayama, Yuuichi Hosokawa, Tetsuhiko Tsuruma, Yasutoshi Kimura, Toru Mizuguchi, Kazuaki Sasaki

International Journal of Clinical Oncology 14 ( 6 ) 529 - 533 2009年12月

Background: UFT is composed of tegafur, a prodrug of 5-fluorouracil, and uracil, at a fixed ratio of 1: 4. UFT is widely used with leucovorin as adjuvant chemotherapy in patients with colon cancer. As reported, UFT/leucovorin should not be taken simultaneously with food because a high fat content will reduce the systemic exposure to the active cytotoxic moiety of UFT. In this single-dose, randomized, two-way crossover study, we investigated the effects of a low-fat Japanese meal on the pharmacokinetics and oral bioavailability of UFT (2 × 100-mg capsules dose in terms of tegafur) and leucovorin (1 × 25-mg tablet). Methods: Patients (n = 12) were randomly assigned to receive both drugs after an overnight fast or 5 min after eating a standard Japanese breakfast (641 kcal), with a 3-day washout period between treatments. Pharmacokinetics (n = 12) were determined for tegafur, 5-fluorouracil, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin). Results: For 5-fluorouracil pharmacokinetics, the maximum plasma concentration and the area under the curve were reduced by 73.7% and 47.4%, respectively, when UFT was taken postprandially, and the maximum plasma concentration and the area under the curve for uracil were reduced by 84.1% and 68.9%, respectively, compared with dosing on an empty stomach. These decreases in the systemic exposure to 5-fluorouracil were quite marked and may have an impact on its antitumor effect. Conclusion: A low-fat meal affects the pharmacokinetics of UFT similarly to a high-fat meal. © 2009 Japan Society of Clinical Oncology.

DOI PubMed

ローカルサーベイランス2007 最新の報告を10年分と比較して

水口徹, 川本雅樹, 目黒誠, 久木田和晴, 永山稔, 今村将史, 木村康利, 信岡隆幸, 古畑智久, 平田公一

日本外科感染症学会雑誌 ( (一社)日本外科感染症学会 ) 6 ( 5 ) 520 - 520 2009年11月

当科における肝切除術における手術創およびドレーン管理

川本雅樹, 水口徹, 久木田和晴, 目黒誠, 永山稔, 信岡隆幸, 木村康利, 古畑智久, 平田公一

日本外科感染症学会雑誌 ( (一社)日本外科感染症学会 ) 6 ( 5 ) 528 - 528 2009年11月

How I do it?肝切除ラウンドチップCUSAによる高度癒着剥離術と新規肝切離法

水口徹, 川本雅樹, 久木田和晴, 目黒誠, 木村康利, 古畑智久, 信岡隆幸, 平田公一

日本臨床外科学会雑誌 ( 日本臨床外科学会 ) 70 ( 増刊 ) 343 - 343 2009年10月

Clinical compliance with an oral uracil/tegafur (UFT) plus leucovorin (LV) regimen as adjuvant chemotherapy in Japanese colorectal cancer patients

Makoto Meguro, Tomohisa Furuhata, Kenji Okita, Toshihiko Nishidate, Gentaro Ishiyama, Yuji Iwayama, Yasutoshi Kimura, Toru Mizuguchi, Koichi Hirata

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER TOKYO ) 14 ( 5 ) 402 - 407 2009年10月 [査読有り]

The combination of oral uracil/tegafur (UFT) plus leucovorin (LV) is widely accepted as adjuvant chemotherapy for stages II and III of colorectal cancer. However, the clinical compliance of Japanese patients with this regimen has not been clearly elucidated to date. A total of 40 Japanese outpatients were treated with oral UFT plus LV as adjuvant chemotherapy following colorectal cancer surgery between January 2005 and June 2007. UFT capsules (300-500 mg/body per day) and LV tablets (75 mg/body per day, administered with each dose of UFT) were to be taken for 28 days, followed by 7 days of rest, with this cycle repeated every 35 days for 6 months or until recurrence. The patients were classified into the following three groups based on compliance: the completed group (n = 21), the modified group (n = 12), and the discontinued group (n = 7). The UFT doses (mean +/- SD) were 267 +/- 35 mg/m(2) in the completed group, 276 +/- 50 mg/m(2) in the modified group, and 288 +/- 22 mg/m(2) in the discontinued group. The UFT dose in the discontinued group tended to be higher than that in the completed group (P = 0.12). The most frequent symptoms of nonhematologic toxicity were appetite loss (45%) and fatigue (45%). There were no hematologic or nonhematologic toxicities of grade 3 or 4. The regimen of oral UFT plus LV produced only low-grade toxicity and was convenient for outpatients. It appears that the initial UFT dose might be associated with the development of toxicity in the oral UFT plus LV regimen.

DOI

同時多発性に発症し異なった組織型を呈した混合型肝癌の1切除例

久木田和晴, 水口徹, 川本雅樹, 目黒誠, 孫誠一, 西舘敏彦, 原田敬介, 沖田憲司, 今村将史, 永山稔, 信岡隆幸, 木村康利, 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 ) 70 ( 増刊 ) 680 - 680 2009年10月

当科における腹腔鏡(補助)下肝切除術の工夫

目黒誠, 水口徹, 川本雅樹, 久木田和晴, 中村幸雄, 西舘敏彦, 沖田憲司, 永山稔, 信岡隆幸, 木村康利, 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 ) 70 ( 増刊 ) 481 - 481 2009年10月

当科における高齢者肝切除症例の検討

川本雅樹, 水口徹, 目黒誠, 久木田和晴, 孫誠一, 永山稔, 西舘敏彦, 沖田憲司, 今村将史, 信岡隆幸, 木村康利, 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 ) 70 ( 増刊 ) 683 - 683 2009年10月

Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice

Takayuki Nobuoka, Toru Mizuguchi, Hideki Oshima, Toshihito Shibata, Shinsuke Kaji, Minoru Nagayama, Makoto Meguro, Toshihiro Mitaka, Koichi Hirata

LIVER INTERNATIONAL ( WILEY-BLACKWELL PUBLISHING, INC ) 29 ( 7 ) 979 - 987 2009年08月 [査読有り]

Background/Aims Urinary trypsin inhibitor (UTI) is an innate anti-inflammatory regulator. It can block the release of inflammatory factors, prevent the cascade reaction of cytokines and inhibit excessive activation of leukocytes. Liver regeneration (LR) is a dynamic molecular phenomenon without inflammation. Many cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), have been implicated in regulating LR. However, the role of UTI in LR is totally unknown. The aim of this study was to elucidate the role of UTI in LR using genetically UTI-deficient mice. Methods We performed 68% hepatectomy, comparing UTI (-/-) and UTI (+/+) mice. Recovery of liver weight was recorded and we calculated labelling indices after 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. A DNA microarray was used to examine gene expression followed by real-time polymerase chain reaction. Serum IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 beta (MIP-1 beta) were measured. Results LR in UTI (-/-) mice was delayed at 36 h after hepatectomy, at which time the DNA profile was different. One hundred and fourteen genes were upregulated and 100 genes were downregulated in UTI (-/-) mice at 36 h after hepatectomy among the 21, 977 mRNAs examined. Furthermore, serum IL-6, IL-10, MCP-1 and MIP-1 beta levels at 36 h after hepatectomy in the UTI (-/-) mice were significantly higher than in the UTI (+/+) mice. Conclusion UTI appears to important cytokine and chemokine regulation in normal liver regeneration.

DOI PubMed

Matrix metalloproteinase-2 expression in stromal tissues is a consistent prognostic factor in stage II colon cancer

Yoshiko Inafuku, Tomohisa Furuhata, Makoto Tayama, Kenji Okita, Toshihiko Nishidate, Toru Mizuguchi, Yasutoshi Kimura, Koichi Hirata

CANCER SCIENCE ( WILEY-BLACKWELL PUBLISHING, INC ) 100 ( 5 ) 852 - 858 2009年05月 [査読有り]

For patients with stage II colon cancer, the usefulness of adjuvant chemotherapy remains controversial. Therefore, it is important to identify high-risk indicators. The biological prognostic factors for recurrence might allow further insight into the optimal treatment strategy for patients with node-negative disease. Matrix metalloproteinase-2 seems to be one of the essential factors for tumor invasion and lymph node metastasis. In this study, we analyzed the expression of cyclooxygenase-2 and matrix metalloproteinase-2 by immunohistochemical staining in 109 patients with stage II colon cancer. A positive correlation was observed between tumor cyclooxygenase-2 and tumor matrix metalloproteinase-2 expression (P = 0.0006) and between tumor cyclooxygenase-2 and stromal matrix metalloproteinase-2 expression (P < 0.0001). Stromal matrix metalloproteinase-2 expression was associated with disease-free survival (P = 0.0095) and was shown to be an independent risk factor for recurrence by multivariate analysis. In addition, we carried out an invasion assay in vitro to investigate whether cyclooxygenase-2 and matrix metalloproteinase-2 affected the tumor-invasive potential of colon cancer cell lines. The invasion assay showed that every cancer cell line acquired invasive potential in coculture with stromal cell lines and the cyclooxygenase-2 inhibitor suppressed this phenomenon by downregulating the matrix metalloproteinase-2 expression of stromal cells. In conclusion, these findings suggest that matrix metalloproteinase-2 expression in stromal cells can be a high-risk indicator for recurrence in patients with stage II colon cancer. (Cancer Sci 2009; 100: 852-858).

DOI

Prognostic Impact of Surgical Complications and Preoperative Serum Hepatocyte Growth Factor in Hepatocellular Carcinoma Patients After Initial Hepatectomy

Toru Mizuguchi, Minoru Nagayama, Makoto Meguro, Toshihito Shibata, Shinsuke Kaji, Takayuki Nobuoka, Yasutoshi Kimura, Tomohisa Furuhata, Koichi Hirata

JOURNAL OF GASTROINTESTINAL SURGERY ( SPRINGER ) 13 ( 2 ) 325 - 333 2009年02月 [査読有り]

The relationship between postoperative complications and survival after hepatectomy is not completely understood. The purpose of this study was to determine if surgical complications would have a prognostic impact and to identify any difference of the prognostic factors between a complication group and complication-free group for hepatocellular carcinoma (HCC) patients after initial hepatectomy. One hundred consecutive HCC patients were analyzed in this study. Operative variables and liver functional markers were compared between the complication group and complication-free group. The diagnostic accuracy for predicting complications was evaluated by the receiver operating characteristic (ROC) curve. The Kaplan-Meier method with log-rank test was employed for survival analysis. Univariate and multivariate analyses were performed to identify the prognostic factors in each group. A total of 45 complications in 32 patients were observed according to the modified Clavien classification. The albumin, gamma-glutamyl transferase, choline esterase, indocyanine green retention rate at 15 min (ICGR(15)), hyaluronic acid, prealbumin, hepatocyte growth factor (HGF), HH15, and LHL15 levels before hepatectomy, operative time, and blood loss were significantly different between the two groups. Multivariate analysis revealed that gamma-glutamyl transferase, ICGR(15), and HGF were independent risk factors for postoperative complications. The values of the areas under the ROC curve for predicting complications proved the significance of the predictions. Although the recurrence-free survival rates were not significantly different, the overall survival rates were significantly different between the two groups. Univariate and multivariate analyses for the overall survival rate showed that the stage of the HCC and HGF for the complication group and tumor size for the complication-free group were independent prognostic factors for overall survival. Postoperative surgical complications could have a prognostic impact on overall survival in HCC patients after initial hepatectomy. Serum HGF could be a factor connected to complications and survival in this group.

DOI

Rapid recovery of postoperative liver function after major hepatectomy using saline-linked electric cautery

Toru Mizuguchi, Tadashi Katsuramaki, Minoru Nagayama, Makoto Meguro, Toshihito Shibata, Shinsuke Kaji, Koichi Hirata

Hepato-Gastroenterology 55 ( 88 ) 2188 - 2192 2008年11月

Background/Aims: The exact effect of heat injury in the residual liver on postoperative liver function is not totally understood. The purpose of this study was to compare postoperative liver function after major liver resection using an argon laser beam coagulator (AR) and that using saline-linked electric cautery (SLC) for vessels and bile duct sealing. Methodology: Between January 2001 and December 2005, thirty patients were analyzed in this study retrospectively. The inclusion criteria were that the patients received hemihepatectomy without vascular and biliary reconstruction in a non-cirrhotic liver. Operative variables and liver functions were compared between the AR method and the SLC method. Results: The clinical profiles of the two groups were almost identical, including preoperative hepatic function. Although there was no difference in most of the intraoperative variables between them, warm ischemic time in the SLC group was shorter than in the AR group (46.53 + 25.42 min vs. 70.47±11.48 min: p=0.003). Albumin and hulirubin levels at 7 days after hepatectomy were not significantly different between the two groups, but low-density lipoprotein (LDL) and apolipoprotein B (ApoB) levels in the SLC group at 7 days after hepatectomy were significantly higher than in the AR group (84.27 ± 14.38 mg/dl vs. 60.21 ± 14.27 mg/dl: p=0.001 69.53 ± 17.18 mg/dl vs. 55.87 ± 9.56 mg/dl: p=0.012, respectively). Conclusion: SLC reduces warm ischemic time during hepatectomy. Furthermore, the rapid recovery of LDL and ApoB levels in the SLC group indicates that the SLC method has potential benefits for postoperative hepatic function. © H.G.E. Update Medical Publishing S.A., Athens-Stuttgart.

PubMed

Laminin α5 mediates ectopic adhesion of hepatocellular carcinoma through integrins and/or Lutheran/basal cell adhesion molecule

Yamato Kikkawa, Ryo Sudo, Junko Kon, Toru Mizuguchi, Motoyoshi Nomizu, Koichi Hirata, Toshihiro Mitaka

Experimental Cell Research ( ELSEVIER INC ) 314 ( 14 ) 2579 - 2590 2008年08月 [査読有り]

Laminins are a diverse group of alpha/beta/gamma heterotrimers formed from five alpha, three beta and three gamma chains; they are major components of all basal laminae (BLs). One laminin chain that has garnered particular interest due to its widespread expression pattern and importance during development is laminin alpha 5. Little is known, however, about the expression and function of laminins containing the alpha 5 chain in human hepatocellular carcinoma (HCC). Here, using a specific antibody, we examined the expression of laminin alpha 5 in normal liver and in HCCs. In normal liver, although laminin alpha 5 was observed in hepatic BLS underlying blood vessels and bile ducts, it was absent from the parenchyma, which may be the origin of HCC. Oil the other hand, laminin alpha 5 deposition was observed throughout all HCCs tested, regardless of tumor grade. in well-differentiated HCCs, it localized along the trabecules of the tumor. In poorly-differentiated HCCs, it was present in surrounding tumor nodules. In HCC cell lilies, laminin alpha 5 heterotrimerized with beta and gamma chains and was secreted into the culture media. To attempt to understand the function of laminins containing alpha 5, the expression of its receptors in HCCs was also determined. In this regard, alpha 3 beta 1/alpha 6 beta 1 integrins and Lutheran/basal cell adhesion molecule (Lu/B-CAM) were expressed in HCC cells. In vitro studies showed that HCC cells readily attached to laminin containing the alpha 5 chain, more so than did primary hepatocytes. in addition to alpha 3 beta 1/alpha 6 beta 1 integrins and Lu/B-CAM, laminin alpha 5 was recognized by integrin alpha 1 beta 1, which also was expressed in HCC cells. These results suggest that laminins containing alpha 5 serve as functional substrates regulating progression of HCC. (C) 2008 Elsevier Inc. All rights reserved.

DOI

Prospective nonrandomized comparison between pylorus-preserving and subtotal stomach-preserving pancreaticoduodenectomy from the perspectives of DGE occurrence and postoperative digestive functions

Emi Akizuki, Yasutoshi Kimura, Takayuki Nobuoka, Masafumi Imamura, Toshihiko Nishidate, Toru Mizuguchi, Tomohisa Furuhata, Koichi Hirata

Journal of Gastrointestinal Surgery 12 ( 7 ) 1185 - 1192 2008年07月

Background: To determine the influence of pylorus preservation after pancreaticoduodenectomy, we compared the postoperative course of subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) and pylorus-preserving pancreaticoduodenectomy (PPPD). Methods: A prospective, nonrandomized comparison of 77 consecutive patients undergoing PPPD (n=37) or SSPPD (n=40) between January 2003 and March 2007 was planned. The early postoperative course, dietary intake, and the incidence of delayed gastric emptying (DGE) were evaluated. Results: SSPPD included significantly more cases of regional lymph node dissection (D2, PPPD 53% vs. SSPPD 80%) and portal vein resection. The median duration of surgery (457 vs. 520 min) was significantly shorter, and blood loss (619 vs. 1,235 ml) was significantly less in PPPD. Regarding postoperative clinical factors, the duration of nasogastric tube intubation (1 vs.1 day), days until solid diet (7 vs. 7 days), and the incidence of DGE (9% vs.10%) were similar in PPPD and SSPPD. However, the postoperative/preoperative body weight ratio (95% vs. 93%) was significantly higher, and the postoperative hospital stay (31 vs. 38 days) was significantly shorter in PPPD (p< 0.05). Conclusions: Despite the bias of the operative factors, the incidence of DGE and postoperative dietary intake after SSPPD was comparable with PPPD, and therefore, pylorus preservation seemed to have no impact on postoperative dietary intake or DGE. © 2008 The Society for Surgery of the Alimentary Tract.

DOI PubMed

膵癌に対する膵頭十二指腸切除術の各種手術手技膵周囲剥離面陰性化を目指した神経叢郭清と門脈合併切除・再建

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

日本消化器外科学会雑誌 ( (一社)日本消化器外科学会 ) 41 ( 7 ) 1013 - 1013 2008年07月

膵と胆管で乳頭粘液性腫瘍が同時重複した一例

永山稔, 木村康利, 今野愛, 信岡隆幸, 古畑智久, 水口徹, 平田公一, 廣川直樹

膵臓 ( (一社)日本膵臓学会 ) 23 ( 3 ) 432 - 432 2008年06月

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年06月

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