胆囊癌组织中nm23H1和PTEN基因蛋白表达及其临床意义

目的:探讨nm23H1和PTEN基因蛋白在胆囊癌中表达的意义.方法:应用免疫组化方法,检测52例胆囊腺癌、20例胆囊腺瘤和10例慢性胆囊炎组织中nm23H1和PTEN表达水平.结果:在胆囊癌中nm23H1和PTEN表达阳性率分别为51.9%和42.3%,其表达阳性率均明显低于胆囊腺瘤和慢性胆囊炎(P＜0.05).nm23H1和PTEN表达与胆囊癌的分化程度、浆膜浸润和转移密切相关(P＜0.05).nm23H1和PTEN蛋白表达呈正相关(γ=0.56,P＜0.05).结论:检测nm23H1和PTEN基因蛋白表达可作为评价胆囊癌生物学行为的参考指标.     

抑癌基因WWOX在肝外胆管癌中的表达

目的:检测WWOX mRNA及其编码蛋白在肝外胆管癌中的表达,分析其临床病理学意义.方法:用Real Time RT-PCR方法定量分析21例胆管癌组织WWOX mRNA表达情况,5例肝移植的正常胆管组织作为对照;采用UIP法染色检测相应病理切片的蛋白表达情况,并比较mRNA和蛋白在不同分级组织中的表达差异.结果:WWOX mRNA在肝外胆管癌中的表达显著低于正常胆管组织(8.936×10~(-7)±3.253×10~(-7) vs 1.079×10~(-6)±1.735×10~(-7),P<0.001),47%表达缺失;蛋白表达的缺失频率为57%,其mRNA及蛋白表达与组织学分级有显著相关(r=-0.583,-0.840,P<0.001),而年龄、性别、术前肝功能及临床分期无显著相关性.低分化胆管癌组织中的表达显著低于分化较好的肿瘤组织(P±<0.05).结论:WWOX表达改变参与胆管癌的发病,可作为预测肝外胆管癌生物侵袭性的有效指标.     

Smac和Ki-67在肝外胆管异型增生组织和癌组织中的表达及意义

目的 探讨Smac和Ki-67在肝外胆管癌发生发展中的作用和临床意义.方法 用免疫组化S-P法检测27例肝外胆管癌组织、10例异型增生组织和5例正常肝外胆管上皮组织中Smac和Ki-67的表达.结果 Smac在正常肝外胆管上皮组织、异型增生组织和癌组织中阳性表达率分别为40%、50%和85.2%,异型增生组织和癌组织中Smac表达差异有统计学意义(P=0.041).Ki-67在正常肝外胆管上皮组织、异型增生组织和癌组织中阳性表达率分别为0、40%和81.5%,正常肝外胆管上皮组织和癌组织中表达差异无统计学意义(P=0.001),异型增生组织和癌组织中表达差异有统计学意义(P=0.038).Smac和Ki-67在异型增生组织和癌组织的表达呈正相关性(r=0.688,P=0.028).Smac和Ki-67的表达与肝外胆管癌组织病理学特征和临床分期无关.结论 Smac和Ki-67参与了肝外胆管癌的发生发展,凋亡和增殖失衡在其过程中起重要作用,Smac和Ki-67可能在异型增生向癌的恶性转化阶段起重要作用.     

Fascin和MMP-9在肝门胆管癌组织中的表达及临床意义

目的:研究Fascin蛋白和基质金属蛋白酶9(matrix metallo proteinase-9,MMP-9)在肝门胆管癌组织中的表达及其与肝门胆管癌的临床生物学行为的关系.方法:应用SP法检测56例肝门胆管癌及14例正常胆管上皮组织中Fascin和MMP-9的表达.结果:Fascin和MMP-9在肝门胆管癌中的表达阳性率都明显高于正常胆管上皮组织(58.9%vs0%,P<0.05)和(73.2%vs14.3%,P<0.05);且Fascin和MMP-9在肝门胆管癌中的表达与肿瘤的组织分化程度、淋巴结转移、门静脉浸润有关(P<0.05);Fascin和MMP-9在肝门胆管癌组织中的表达呈正相关(P<0.05).结论:Fascin和MMP-9在肝门胆管癌的进展、转移中起重要作用,两者之间起相互协同促进作用.     

大肠癌组织nm23/NDPK及p53表达的意义

研究表明,ｎｍ２３基因的表达与多种实验性肿瘤［１,２］及人类恶性肿瘤［３－５］的转移潜能密切负相关,提示它是一种能抑制肿瘤转移表型的转移抑制基因．ｐ５３在多种肿瘤中均有过度表达,并与肿瘤分化、转移和预后有关．我们应用免疫组织化学方法检测了大肠癌中ｎｍ２３／ＮＤＰＫ和ｐ５３的表达情况,以分析其与大肠癌的病理特征和临床意义的关系．１　材料和方法１．１　材料　外科手术切除大肠癌标本４８例,其中结肠癌２１例,直肠癌２７例,组织病理学分型为高分化腺癌２１例,中分化腺癌１８例,低分化腺癌９例．组织经中性福尔…     

CD66c在肝外胆管癌中的表达及其意义

目的 观察CD66c mRNA在肝外胆管癌(EHCC)组织中的表达,并探讨其与EHCC临床病理特征之间的关系.方法 采用逆转录-聚合酶链反应(RT-PCR)法检测CD66c mRNA在30例EHCC组织中的表达情况.结果 EHCC组织淋巴结转移组和无转移组中CD66c mRNA表达分别为0.13±0.03和0.08±0.02:EHCC组织低分化组和高中分化组中CD66c mRNA表达分别为0.24±0.02和0.15±0.04,差异有统计学意义(P＜0.05);Ⅱ、Ⅲ期和Ⅰ期肝外胆管癌组织中CD66c mRNA表达分别为0.52±0.06和0.16±0.02,差异有统计学意义(P＜0.05).结论 CD66c可能对EHCC的发生和发展起促进作用.     

胃癌组织中C-erbB-2、p53、PCNA和P-gp的表达及其临床意义

应用免疫组化198例胃癌组织中C-erbB-2、p53、增殖细胞核抗原（PCNA）和P-糖蛋白（P-gp）进行联合检测,并结合临床资料进行分析。认为联合检测C-erbB-2、p53、PCNA和P-gp对判断胃癌的发展、恶性程度、淋巴结转移、临床耐药及预后具有重要意义。     

bcl—2蛋白在肝肿瘤组织的表达及意义

目的 探讨抗凋亡基因ｂｃｌ－２蛋白在常见肝肿瘤发生中的作用。方法 应用ｂｃｌ－２癌蛋白单克隆抗体对６４例四种类型的肝恶性肿瘤进行ＬＳＡＢ免疫组织化学标记。结果 １６．２％（６／３７）的肝细胞癌，６９．２％（９／１３）的胆管细胞癌，２０．０％（１／５）的肝母细胞瘤和２２．２％（２／９）肝转移癌呈ｂｃｌ－２癌蛋白阳性表达，其中胆管细胞癌的阳性率显著高于其癌旁组织（Ｐ值〈０．０５）和肝细胞癌（Ｐ值〈０．     

P21、nm23和bcl-2在大肠癌组织中的表达

目前．大肠癌的癌基因改变正日益受到人们的重视。2001～2003年，我们应用免疫组织化学方法检测原癌基因(P^21)、转移抑制基因(nm23)和凋亡抑制基因(bcl-2)在大肠癌组织中的表达，并探讨其在大肠癌生物学行为方面的意义。     

CD24 expression predicts distant metastasis in extrahepatic bile duct cancer

AIM: To evaluate the prognostic significance of CD24 expression in patients undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Eighty-four patients with EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to a median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine chemotherapy for radiosensitization during radiotherapy. CD24 expression was assessed with immunohistochemical staining on tissue microarray. Clinicopathologic factors as well as CD24 expression were evaluated in multivariate analysis for clinical outcomes including loco-regional recurrence, distant metastasisfree and overall survival. RESULTS: CD24 was expressed in 36 patients (42.9%). CD24 expression was associated with distant metastasis, but not with loco-regional recurrence nor with overall survival. The 5-year distant metastasis-free survival rates were 55.1% and 29.0% in patients with negative and positive expression, respectively (P=0.0100). On multivariate analysis incorporating N stage, histologic differentiation and CD24 expression, N stage was the only significant factor predicting distant metastasis-free survival (P=0.0089), while CD24 expression had borderline significance (P=0.0733). In subgroup analysis, CD24 expression was significantly associated with 5-year distant metastasis-free survival in node-positive patients (38.4% with negative expression vs 0% with positive expression, P=0.0110), but not in nodenegative patients (62.0% with negative expression vs 64.0% with positive expression,P=0.8599). CONCLUSION: CD24 expression was a significant predictor of distant metastasis for patients undergoing curative resection followed by adjuvant chemoradiotherapy especially for node-positive EHBD cancer.     

Intraductal ultrasonography for the diagnosis of proximal invasion in extrahepatic bile duct cancer

Intraductal ultrasonograpy (IDUS) was performed on 22 patients with extrahepatic bile duct cancer, using the percutaneous transhepatic approach. Intraductal ultrasonograpy images of the proximal invasion of the bile duct cancer were defined. In addition, three patients were examined through the peroral approach, to try to diagnose whether or not the cancer invaded to the bifurcation of the hepatic duct. Intraductal ultrasonograpy images obtained through the percutaneous approach could be classified into three patterns, types 1, 2 and 3, according to the features of the interior surface of the bile duct and the thickness of the bile duct wall. Type 1 images, which did not show protrusions into the bile duct lumen and had a bile duct wall of even thickness, were not likely to show bile duct cancer. Type 2 images showed protrusions of the tumour into the bile duct lumen and the surfaces of the protrusions were irregular. Type 3 images showed single or multiple low echoic papillary masses in the bile duct. Using the peroral technique, we considered all three cases to be type 1 and could diagnose that cancer had not invaded to the bifurcation of the hepatic ducts. From the results of this study, we suggest that proximal invasion of extrahepatic bile duct cancer can be diagnosed using IDUS.     

Neuroendocrine carcinoma of the extrahepatic bile duct: A case report

Neuroendocrine carcinoma(NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma(cT 4N1M0, c Stage Ⅳ). He underwent a right hepatectomy combined with extrahepatic bile duct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis.     

Frozen section and permanent diagnoses of the bile duct margin in gallbladder and bile duct cancer

Hypothesis. Frozen section diagnosis and permanent diagnosis of bile duct margin predict local recurrence after surgical resection of gallbladder or bile duct carcinoma. Design. Retrospective review. Setting. University, tertiary care. Patients. A total of 20 patients underwent frozen section diagnosis of bile duct margin for resection of gallbladder and bile duct carcinoma. Main outcome. Diagnosis of frozen and permanent section of bile duct margin, and local recurrence. Results. The permanent diagnosis was identical in 15 patients but changed in 5 (from positive to negative in 3 and from negative to positive in 2). The reasons for these changes were overdiagnosis (mucosal lesions in two and mesenchymal components in another) and new recognition of malignant cells on permanent section in the other two. In seven patients with a positive bile duct margin by permanent histology, mucosal spread was evident in two and involvement of the subepithelial layer was present in the other five. No local recurrence occurred in the two patients with epithelial spread and four of the five with subepithelial infiltration. Conclusions. Frozen section and permanent diagnoses of the bile duct margin in gallbladder and bile duct carcinoma may be inconsistent in 25% of patients due to overdiagnosis of frozen section or new recognition of cancer cells by permanent histology. In situ carcinoma does not always produce local recurrence, while cancer cells in the subepithelial layer strongly predict occurrence of local recurrence.     

Limitations of three-dimensional intraductal ultrasonography in the assessment of longitudinal spread of extrahepatic bile duct carcinoma

We investigated the utility and limitations of three-dimensional intraductal ultrasonography (3D-IDUS), for the assessment of the extent of longitudinal cancer spread to the hepatic side by extrahepatic bile duct carcinoma. In eight patients with extrahepatic bile duct carcinoma, 3D-IDUS was used to assess longitudinal cancer extension to the hepatic side prior to resection. When the linear dimension of 3D-IDUS showed bile duct wall thickening that was connected to the tumor and which became thin at a point, it was determined to be the front formation of longitu-dinal cancer extension. The findings were examined in relation to histologic information from the resected specimen. Although 3D-IDUS showed front formation of wall thickening in two patients, it accurately reflected the histological margin of the longitudinal cancer extension in only one patient. In the other patient, the wall thickening was longer than the histological margin. When 3D-IDUS showed bile duct wall thickening without front formation (n = 2), the wall thickening was longer than the histological margin of the longitudinal cancer extension. Even when 3D-IDUS did not show wall thickening (n = 4), one of these patients showed cancer spread histologically. As a result, the accuracy in assessing longitudinal cancer extension by 3D-IDUS was only 50%. Even if the linear dimension of 3D-IDUS demonstrated front formation of thickening of the bile duct, it reflected not only cancer extension but also inflammatory wall thickening. Received: March 21, 2000 / Accepted: July 7, 2000     

胆道肿瘤组织中ubiquitin的表达及临床意义

目的研究人胆道系统肿瘤中泛素（ubiquitin）蛋白的表达与胆道系统肿瘤不同病理分型的关系及其临床意义。方法采用免疫组织化学法结合蛋白印迹技术检测人胆道肿瘤组织、正常胆道组织及炎性组织中泛素蛋白的表达,分析人胆道肿瘤组织中泛素蛋白的表达情况与不同临床病理情况之间的相关性。结果人胆道肿瘤组织中泛素蛋白的表达显著高于正常组织及炎性组织中泛素蛋白的表达（P〈0．05）。泛素蛋白的表达与病理组织学分级有明显相关性（P〈0．05）。结论泛素蛋白在人胆道肿瘤组织中表达水平升高,可能与胆道系统肿瘤的恶性程度、疾病的进程有密切的关系。     

肝细胞癌p53及nm23-H1 mRNA表达的意义

目的探讨ｐ５３,ｎｍ２３Ｈ１与原发性肝细胞癌（ＨＣＣ）发生发展的关系．方法运用原位分子杂交技术对４９例ＨＣＣ中ｐ５３和ｎｍ２３Ｈ１基因ｍＲＮＡ进行检测,并结合临床病理特征进行分析．结果ｐ５３ｍＲＮＡ杂交阳性２３例,占４６９％;ｐ５３ｍＲＮＡ过表达与肿瘤的肝内转移．包膜侵犯及Ｅｄｍｏｎｄｓｏｎ分级相关（Ｐ＜００５）;ｎｍ２３Ｈ１ｍＲＮＡ阳性表达２７例,占５５１％;ｎｍ２３Ｈ１ｍＲＮＡ表达与肿瘤肝内转移及ＴＮＭ分期呈负相关（Ｐ＜００５）;同时发现ｐ５３ｍＲＮＡ过表达和ｎｍ２３Ｈ１ｍＲＮＡ低表达在ＨＣＣ肝内转移中具有协同作用．结论ｐ５３和ｎｍ２３Ｈ１参与ＨＣＣ的发生发展,ｐ５３过表达及ｎｍ２３Ｈ１低表达提示ＨＣＣ肝内转移．     

Diagnostic value of transpapillary biopsy using double lumen introducer for determination of mucosal extent in extrahepatic bile duct cancer

Diagnosis of the upstream extent of extrahepatic bile duct cancer has been difficult via the transpapillary approach, due to the difficulty of obtaining a biopsy sample above the stricture. We developed a new biopsy technique that allows a sample to be taken above the stricture, and prospectively evaluated the new technique's utility. Twenty‐four consecutive patients diagnosed as having possible extrahepatic bile duct cancer by endoscopic retrograde cholangiopancreatography and other imaging tests were included in the study. They initially underwent endoscopic placement of a nasobiliary drainage tube. After improvement of jaundice and cholangitis, the cholangiogram obtained via the tube was examined and transpapillary biopsy was performed using a double lumen catheter under fluoroscopic guidance. The biopsy sampling in the stricture was successful in all cases, and pathological diagnosis was confirmed in all cases. The success rate of the method of upstream diagnosis was also sufficient in cases in which stricture was located below the middle extrahepatic bile duct. However, it was relatively low in cases whose stricture was located in the upper extrahepatic bile duct. Biopsy sampling in the hepatic hilum was also difficult. The transpapillary biopsy technique is useful for determination of the upstream extent of extrahepatic bile duct cancer, especially in cases in which stricture is located in the lower extrahepatic bile duct. Compared to the percutaneous transhepatic approach, it is less invasive and can shorten the preoperative period. It was also seen to be relatively safe, easy and convenient.     

Metachronous double cancer of the gallbladder and common bile duct

We report a rare case of metachronous double cancer of the biliary tract. At age 59 years, a man had undergone a cholecystectomy and resection of the liver bed for gallbladder cancer pathologically diagnosed as papillary adenocarcinoma, in 1997. Four years later, he was admitted to our hospital with jaundice. At first, we suspected lymph node metastasis of the gallbladder cancer along the common bile duct. But abdominal computed tomography demonstrated circular wall thickness of the common bile duct, so primary bile duct cancer was strongly suspected. Thus, extended right hepatectomy and pancreaticoduodenectomy were performed after right portal vein embolization. The pathological diagnosis of the resected specimen was well-differentiated tubular adenocarcinoma, and this case was clarified to be metachronous double cancer. A review of the literature regarding double cancer of the biliary tract is presented following this case report. We showed that half of 30 cases of double cancer of the biliary tract were not associated with pancreaticobiliary maljunction, including all 6 metachronous cases.