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Regional lymphadenectomy for gallbladder cancer: Rational extent, technical details, and patient outcomes

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World Journal of Gastroenterology 2012年第22期18卷 2775-2783页

作者： yoshio shirai Toshifumi Wakai Jun Sakata Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences

AIM: To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival. METHODS: A total of 152 patients with gallbladder cancer who underwent a minimum of "extended" portal lymph node dissection (defined as en bloc removal of the first-and second-echelon nodes) from 1982 to 2010 were retrospectively analyzed. Based on previous studies, regional lymph nodes of the gallbladder were divided into first-echelon nodes (cystic duct or pericholedochal nodes), second-echelon nodes (node groups posterosuperior to the head of the pancreas or around the hepatic vessels), and more distant nodes. RESULTS: Among the 152 patients (total of 3352 lymph nodes retrieved, median of 19 per patient), 79 patients (52%) had 356 positive nodes. Among nodepositive patients, the prevalence of nodal metastasis was highest in the pericholedochal (54%) and cystic duct (38%) nodes, followed by the second-echelon node groups (29% to 19%), while more distant node groups were only rarely (5% or less) involved. Disease-specific survival after R0 resection differed according to the nodal status (P < 0.001): most node-negative patients achieved long-term survival (median, not reached; 5-year survival, 80%), whereas among nodepositive patients, 22 survived for more than 5 years (median, 37 mo; 5-year survival, 43%). CONCLUSION: The rational extent of lymphadenectomy for gallbladder cancer should include the first-and second-echelon nodes. A considerable proportion of node-positive patients benefit from such aggressive lymphadenectomy.

关键词： Gallbladder neoplasms Lymphatic metasta-sis Lymph node excision Prognosis Radical surgery

"Extended" radical cholecystectomy for gallbladder cancer:Long-term outcomes, indications and limitations

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World Journal of Gastroenterology 2012年第34期18卷 4736-4743页

作者： yoshio shirai Jun Sakata Toshifumi Wakai Taku Ohashi Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental SciencesNiigata City 951-8510Japan

AIM:To delineate indications and limitations for "ex tended" radical cholecystectomy for gallbladder cancer:a procedure which was instituted in our department in 1982. METHODS:Of 145 patients who underwent a radi cal resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystec tomy, which involved en bloc resection of the gallblad der, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first-and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1 2). athological findings were documented according tothe American Joint Committee on Cancer Cancer Stag ing anual (7th edition). RESULTS:he primary t mor as classified as patho-logical T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giv ing an in hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the p classification ( < 0.001) and the nodal status ( = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tu mors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1 2 resection, distant metastasis, or extensive extrahepatic organ involve ment died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4

关键词： Gallbladder neoplasms Radical surgery Hepatectomy Bile duct resection Lymph node excision Prognosis

Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2005年第44期11卷 7024-7027页

作者： Jun Sakata yoshio shirai Toshifumi Wakai Tatsuya Nomura Eiko Sakata Katsuyoshi Hatakeyama Division of Digestive and General Surgery

AIM： To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage （PTBD） for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature. METHODS： A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 too. The English language literature （PubMed, National Library of Medicine, Bethesda, MD, USA）, from .lanuary 1966 through December 2004, was reviewed. RESULTS： Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau （6%） at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma （including our three patients）, two survived for more than 5 years after the excision of isolated catheter tract metastases. CONCLUSION： Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.

关键词： Neoplasm seeding Extrahepatic cholangiocarcinoma Percutaneous transhepatic biliary drainage Malignant biliary obstruction Surgery Prognosis

Low preoperative platelet counts predict a high mortality after partial hepatectomy in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第37期11卷 5888-5892页

作者： Kazuhiro Kaneko yoshio shirai Toshifumi Wakai Naoyuki Yokoyama Kohei Akazawa Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Niigata Japan Department of Medical Informatics Niigata University Medical and Dental Hospital Niigata Japan

AIM： To assess the validity of our selection criteria for hepatectomy procedures based on indocyanine green disappearance rate （KICG）, and to unveil the factors affecting posthepatectomy mortality in patients with hepatocellular carcinoma （HCC）. METHODS： A retrospective analysis of 198 consecutive patients with HCC who underwent partial hepatectomies in the past 14 years was conducted. The selection criteria for hepatectomy procedures during the study period were KICG≥0.12 for hemihepatectomy, KICG≥0.10 for bisegmentectomy, KCG≥0.08 for monosegmentectomy, and KICG≥ 0.06 for nonanatomic hepatectomy. The hepatectomies were categorized into three types： major hepatectomy （hemihepatectomy or a more extensive procedure）, bisegmentectomy, and limited hepatectomy. Univariate （Fishers exact test） and multivariate （the logistic regression model） analyses were used. RESULTS： Postoperative mortality was 5% after major hepatectomy, 3% after bisegmentectomy, and 3% after limited hepatectomy. The bhree percentages were comparable （P = 0.876）. The platelet count of ≤ 10× 10^4/μL was the strongest independent factor for postoperative mortality on univariate （P = 0.001） and multivariate （risk ratio, 12.5; P= 0.029） analyses. No patient with a platelet count of 〉7.3× 10^4/μL died of postoperative morbidity, whereas 25% （6/24 patients） of patients with a platelet count of ≤7.3×10^4/μL died （P〈0.001）. CONCLUSION： The selection criteria for hepatectomy procedures based on KICG are generally considered valid, because of the acceptable morbidity and mortality with these criteria. The preoperative platelet count independently affects morbidity and mortality after hepatectomy, suggesting that a combination of KICG and platelet count would further reduce postoperative mortality.

关键词： Hepatocellular carcinoma Hepatectomy Morbidity Mortality Indocyanine green clearance test Blood platelet count

Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

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World Journal of Gastroenterology 2007年第33期13卷 4480-4483页

作者： Masayuki Nagahashi yoshio shirai Toshifumi Wakai Jun Sakata Yoichi Ajioka Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medicaland Dental Sciences Niigata Japan Division of Molecular and Diagnostic Pathology Niigata University Graduate School of Medical and Dental Sciences Asahimachi-dori Niigata City Japan

AIM： To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS： Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power （×200） fields with the highest lymphatic vessel density （LVD）, termed ＂hot spots＂; were identified for each layer （mucosa, muscle layer, and perimuscular connective tissue）. In individual hot spots, the LVD and relative lymphatic vessel area （LVA） were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses. RESULTS： In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2, 35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively. Thus, both the LVD and LVA differed significantly （P 〈 0.001 and P 〈 0.001, respectively; KruskaI-Wallis test） among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most （98 of 108） of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer. CONCLUSION： The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 （tumor invading the perimuscular connective tissue） or more advanced gallbladder carcinoma.

关键词： Gallbladder Lymphatic vessels Monoclonal antibody D2-40 Gallbladder neoplasms Lymphaticmetastasis

Narrow portion of the terminal choledochus is a cause of upstream biliary dilatation in patients with anomalous union of the pancreatic and biliary ducts

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World Journal of Gastroenterology 2005年第41期11卷 6503-6507页

作者： Tatsuya Nomura yoshio shirai Toshifumi Wakai Naoyuki Yokoyama Jun Sakata Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences 1 Asahimachi-doriNiigata951-8510Japan

AIM: To clarify the pathogenesis of biliary dilatation associated with anomalous union of the pancreatic and biliary ducts (AUPBD).METHODS: Direct cholangiopancreatograms of 350 adult patients with or with suspicion of hepatobiliary or pancreatic disorders were reviewed. AUPBD was diagnosed cholangiopancreatographically, when the pancreaticobiliary ductal union was located above the narrow distal segment of the bile duct, which represents the action of the sphincter of Oddi. The narrow portion of the terminal choledochus was defined as symmetrical stricture of the common bile duct just above the pancreaticobiliary ductal ***: AUPBD was found in 36 patients. Among cholangiopancreatographic features, the narrow portion of the terminal choledochus was the most pathognomonic for AUPBD (accuracy, 98%); it was present in 29 (81%)patients with AUPBD, but was not found in any patients without AUPBD. Among patients with AUPBD, biliary dilatation (＞10 mm) was more frequent in those with the narrow portion of the terminal choledochus (23/29)than in those without (2/7; P = 0.018) AUPBD. Among the patients with both AUPBD and the narrow portion of the terminal choledochus, there was a strong negative correlation between the minimum diameter of the narrow portion and the maximum diameter of the choledochus (r = -0.78, P＜0.001), suggesting that the degree of biliary narrowing at the narrow portion correlates with that of upstream biliary ***: The narrow portion of the terminal choledochus, a pathognomonic radiologic feature of AUPBD, may be a cause of biliary dilatation in patients with AUPBD.

关键词： Anomalous Biliary dilatation Congenital biliary dilatation Congenital choledochal cyst Terminal choledochus Cholangiopancreatography

Genetic changes of p53,K-ras,and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

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World Journal of Gastroenterology 2008年第1期14卷 70-75页

作者： Masayuki Nagahashi Yoichi Ajioka Istvan Lang Zoltan Szentirmay Miklos Kasler Hiroto Nakadaira Naoyuki Yokoyama Gen Watanabe Ken Nishikura Toshifumi Wakai yoshio shirai Katsuyoshi Hatakeyama Masaharu Yamamoto Division of Molecular and Diagnostic Pathology Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan Department of Medical Oncology "B" National Institute of Oncology Budapest H-1122 Hungary Department of Molecular Pathology National Institute of Oncology Budapest H-1122 Hungary Department of Head and Neck Surgery National Institute of Oncology Budapest H-1122 Hungary Department of Nursing Faculty of Nursing Social Welfare and Psychology Niigata Seiryo University Niigata 951-8510 Japan Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan Department of Community Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan

AIM： To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS： We examined 42 cases of gallbladder carcinoma： 22 Japanese and 20 Hungarian cases, p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of flve-microsatellite markers （BAT-25, BAT-26, D2S123, DSS346, and D17S250）. RESULTS： Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases （11/22 vs 6/18, P = 0.348）. Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant （0/11 vs 2/6,P = 0.110）. K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 （42.1%） ]apanese cases were MSI-high （presence of novel peaks in more than one of the five loci analyzed）, whereas only 1 of 15 （6.7%） Hungarian cases was MSI-high （P = 0.047）. CONCLUSION： It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

关键词： Gallbladder Gallbladder Neoplasms K-ras Microsatellite instability p53

Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis

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World Journal of Hepatology 2011年第1期3卷 15-23页

作者： Hirokazu Kawai Minoru Nomoto Takeshi Suda Kenya Kamimura Atsunori Tsuchiya Yasushi Tamura Masahiko Yano Masaaki Takamura Masato Igarashi Toshifumi Wakai Satoshi Yamagiwa Yasunobu Matsuda Shogo Ohkoshi Isao Kurosaki yoshio shirai Masahiko Okada Yutaka Aoyagi Department of Clinical Laboratory Niigata University Medical and Dental Hospital Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Department of Medical Technology Niigata University Graduate School of Health Sciences Division of Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences

AIM:To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis(NASH) focusing on multicentric occurrence (MO) of ***:We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH *** clinical features were implicated with reference to the literature ***:MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC(2 males and 2 females).One patient had synchronous MO;an advanced HCC,two well-differentiated HCCs and a dysplastic nodule,followed by the development of metachronous MO of *** other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic *** these three patients,one had synchronous MO,one had metachronous MO and the other had both synchronous and metachronous *** were no obvious differences between the patients with or without MO in terms of liver function tests,tumor markers and anatomical extent of *** the other hand,all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity,type 2 diabetes mellitus(T2DM),hypertension and *** these conditions were not limited to MO of HCC,all the conditions were met in only one of eight patients without MO of ***,concurrence of these conditions may be a predisposing situation to synchronous MO of *** particular,old age,T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the ***:The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this *** investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.

关键词： Nonalcoholic steatohepatitis Hepatocellular carcinoma Multicentric occurrence

A Case of Male Anorgasmia with Cerebral Infarction

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Open Journal of Urology 2012年第3期2卷 151-152页

作者： Masato shirai yoshio Kawachi Shigeto Yanada Hajime Watanabe Youichiro Toyonaga Sousuke Sugimura Toru Sakurai Makoto Fujime Department of Urology Juntendo University Urayasu Hospital Chiba Japan

Objective: The deficit of male orgasm is an unusual clinical condition. This is a case report on secondary male anorgasmia with cerebral infarction. Material and Method: The patient was a 55-year-old man who had suffered from male anorgasmia, acquired type. The patient had a normal erectile response, but ejaculated without any sensation of orgasm. The patient underwent an evaluation by a psychiatrist and an urologist trained in sexual medicine. Result: The results of physical, psychological, and laboratory examination were normal. Brain MRI revealed cerebral infarction at bilateral parietal lobes and frontal lobes. Conclusion: There is a possibility that these brain regions are related to male orgasmic dysfunction.

关键词： Male Anorgasmia Orgasmic Dysfunction Cerebral Infarction Brain Imaging