β-catenin、E-cadherin和Ki67在小鼠大肠癌中的表达及其意义

目的 :探讨小鼠正常肠黏膜组织与大肠癌组织β-catenin、E-cadherin和Ki67表达情况及其关系。方法:采用氧化偶氮甲烷诱导建立小鼠大肠癌模型;运用SP免疫组织化学方法检测20只正常小鼠肠黏膜组织与20只小鼠大肠癌组织中β-catenin、E-cadherin和Ki67的表达情况,并分析三者表达的相关性。结果:β-catenin在小鼠大肠癌组织中的异常表达率(70%)较正常小鼠肠黏膜组织(5%)显著升高(P0.001);E-cadherin在小鼠大肠癌组织中的阳性率(45%)较正常小鼠肠黏膜组织(95%)显著降低(P0.001);Ki67在小鼠大肠癌组织中的阳性率(80%)较正常小鼠肠黏膜组织(15%)显著升高(P0.001)。小鼠大肠癌组织中Ki67的阳性表达与β-catenin的异常表达呈正相关(P0.001),与E-cadherin的阳性表达呈负相关(P0.001)。结论:E-cadherin低表达、Ki67高表达以及β-catenin异常表达可能在大肠癌的发生发展和转移过程中发挥着重要作用。     

Transforming growth factor-β and prostate cancer

Summary This review focuses on the possible role of transforming growth factor- isoforms 1–3 (TGF) in prostate cancer. TGF1 appears to inhibit the cellular proliferation of normal prostate cells. Surprisingly, TGF1 is overexpressed in prostate cancer. To help explain this apparent paradox, it has been revealed that with tumor progression, prostate cancer cells acquire reduced sensitivity to the growth-inhibitory effects of TGF1. Aberrations of the TGF1 signaling pathway at the prereceptor, receptor, or postreceptor level may lead to prostate cancer cell resistance to TGF1 growth inhibition. Indirectly, elevated levels of TGF1 may induce host effects that may be beneficial to prostate tumor growth by suppressing the immune system, promoting angiogenesis and extracellular matrix formation, and enhancing metastatic potential. Consequently, TGF1 appears to be important in prostate carcinogenesis and tumorigenicity. TGF2 and TGF3 are only briefly presented as very little is known about their role in prostate cancer.     

Clinical and Genetic Analysis of Noncancerous and Cancerous Biliary Epithelium in Patients with Pancreaticobiliary Maljunction

We analyzed clinical features and genetic alterations in the noncancerous and cancerous biliary lesions obtained from pancreaticobiliary maljunction (PBM) patients. Gallbladder (GB) and bile duct (BD) lesions were obtained surgically from 36 patients with PBM, and polymerase chain reaction (PCR) methods were used to examine for mutations of the K-ras gene and the p53 gene and for microsatellite instability (MSI). The 36 cases were clinically classified into two types according to whether extrahepatic bile duct dilatation was present: a congenital choledochal dilatation (CCD) group (n = 20) and a noncongenital choledochal dilatation (NCCD) group (n = 16). In the NCCD group, all 16 GB specimens exhibited hyperplastic, dysplastic, and cancerous (n = 9) lesions, but no pathological lesions were detected in the 12 BD specimens. On the other hand, in the CCD group, pathological examination revealed lesions, including 8 cancerous lesions, in 60% of the 20 GB specimens and lesions, and including 8 cancerous lesions, in 65% of the 20 BD specimens. K-ras mutations and MSI were detected in 33.3% and 0%, respectively, of 9 hyperplastic lesions, 28.6% and 85.7%, respectively, of 7 dysplastic lesions, and 60.0% and 80.0%, respectively, of 25 cancerous lesions (p <0.05; MSI in hyperplasia vs. dysplasia and cancer). There was no difference of the frequency in K-ras mutations and MSI between the NCCD and CCD groups. By contrast, p53 mutations were detected only in the cancerous GB lesions of both types, the rate being 35.3%. Genetic alterations of K-ras, MSI, and p53 are strongly associated with biliary tract cancer in PBM patients. MSI appears to contribute to carcinogenesis in the biliary tract mucosa of PBM patients, and p53 mutations may be related to the development of GB cancer in the CCD group.     

Suprabasal expression of Ki-67 antigen as a marker for the presence and severity of oral epithelial dysplasia

BACKGROUND: Suprabasal expression of Ki-67 is assessed as a marker for oral dysplasia. The study involved non-neoplastic epithelium adjacent to 74 oral squamous cell carcinomas. METHODS: An immunohistochemical technique was carried out (peroxidase-antiperoxidase) with the monoclonal antibody MIB-1. Epithelial expression of Ki-67 was classified as being absent, basal, and suprabasal. The epithelium was normal in 19 cases, hyperplastic in 38 cases, and dysplastic in 37 cases. The dysplasia was slight in 20 cases, moderate in 12 cases, and severe in 5 cases. RESULTS: The results of the expression of Ki-67 were in normal epithelium, basal expression 9 cases, absent 10 cases; in hyperplastic epithelium, basal expression 18 cases, absent 20 cases; in dysplastic epithelium, basal and suprabasal expression (always jointly) 27 cases, absent 10 cases; all the severe and moderate dysplasia cases expressed suprabasal Ki-67. A significant association was observed between the presence (p <.0001) and severity (p <.007) of the dysplasia and the suprabasal expression of Ki-67.     

人膀胱移行细胞癌上皮间质转化与胸腺素β4的关系

目的 探讨人胸腺素β4(Tβ4)与膀胱移行细胞癌(BTCC)上皮-间质转化的相关性,以及与临床病理特征之间的关系.方法 选用膀胱移行细胞癌手术切除标本60例,每例标本均选用癌组织中心、癌旁组织及其远端正常黏膜对照.采用定量逆转录-聚合酶链反应(RT-PCR)、Western blot和免疫组织化学技术检测切除标本中的Tβ4、整合素连接激酶(ILK)、E-cadherin和β-catenin的表达,并分析与各临床病理因素之间的关系.结果 Tβ4在BTCC组织中的表达明显高于正常黏膜(91.7%比15.0%,P<0.05),其在深层浸润组中的表达高于浅层浸润组(97.4%比81.00,P<0.05);ILK在BTCC组织中的表达明显高于正常黏膜(80.0%比18.3%,P<0.05);β-catenin在BTCC组织中的表达高于正常黏膜(76.7%比26.7%,P<0.05);E-cadherin在BTCC组织中的表达明显低于正常黏膜(30.0%比90.0%,P<0.05);Tβ4与E-cadherin表达呈负相关,与ILK、β-catenin表达呈正相关.结论 胸腺索β4与膀胱移行上皮癌分化和转移有关,可能通过调控上皮-间质转化从而在膀胱移行上皮癌的侵袭转移过程中发挥作用.     

The Prognostic Value of E-Cadherin, α-, β-, and γ-Catenin in Urothelial Cancer of the Upper Urinary Tract

Objectives

To determine the value of loss of the expression of E-cadherin and cadherin-associated molecules as useful markers for both prognosis and bladder recurrence in patients with upper urinary tract cancer.

Materials and methods

In 61 paraffin-embedded nephroureterectomy specimens, the expression of E-cadherin and α-, β-, and γ-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance, Kaplan-Meier survival curves were calculated and compared by the log-rank test. A multivariate test was performed to detect prognostic markers.

Results

Normal expression was found in 32 cases (52.5%) for E-cadherin, 41 cases (67.2%) for α-catenin, 42 cases (68.9%) for β-catenin, and 31 cases (50.8%) for γ-catenin. The expression patterns of E-cadherin and α-, β- and γ-catenin were significantly correlated with each other. Survival analysis showed a significant difference between normal and aberrant expression in each staining. Multivariate analysis revealed that tumor stage and the expression of E-cadherin were independent prognostic factors for cause-specific survival. In contrast, there was no significant correlation between the expression of E-cadherin and α-, β-, and γ-catenin and bladder recurrence.

Conclusion

Our data suggest E-cadherin may be a good prognostic marker for patients with upper urinary tract cancer.     

联合检测泛素连接酶Cullin1和基质金属蛋白酶MT4-MMP在乳腺癌组织中的表达及临床意义

目的探究泛素连接酶Cullin1和基质金属蛋白酶MT4-MMP在不同类型乳腺癌组织中表达情况及临床意义。 方法2015年1月至8月,选择徐州市肿瘤医院80例乳腺癌组织及其对应的癌旁正常乳腺组织,应用免疫组织化学法和Western blotting法分别检测其中Cullin1和MT4-MMP的表达情况,并分析其相关性。 结果Cullin1、MT4-MMP蛋白在乳腺癌组织中的表达均高于癌旁正常乳腺组织,差异均有统计学意义（77.5% vs 28.8%,67.5% vs 17.5%,χ²=38.174、40.921,均P<0.01）;在乳腺癌组织中,Cullin1及MT4-MMP蛋白的表达呈正相关（P<0.05）。Cullin1及MT4-MMP在乳腺癌中的蛋白表达在分子分型、腋窝淋巴结是否转移及TNM分期组间差异有统计学意义（P<0.05）;在患者年龄、肿瘤大小、肿瘤部位、是否复发转移组间差异无统计学意义。 结论Cullin1及MT4-MMP可能参与了乳腺癌的形成及发展过程,且两者在此过程中有一定协同作用。在分型差、分期晚的乳腺癌中,Cullin1及MT4-MMP更高的表达状态提示其可能成为新的乳腺癌恶性程度指标。     

Parathyroid hormone inhibits the expression of membrane-type matrix metalloproteinase-1 (MT1-MMP) in osteoblast-like MG-63 cells

Parathyroid hormone (PTH) can stimulate bone resorption by increasing the activity and the number of osteoclasts in bone tissue by several mechanisms. Recently, osteoblast-derived membrane-type matrix metalloproteinase-1 (MT1-MMP) has been implied to play an important role in the process of bone resorption by degrading bone matrix. In the present study, we observed the effects of PTH (1-34) on MT1-MMP production, and the role of the protein kinase A (PKA) and protein kinase C (PKC) pathways in the regulation of MT1-MMP in cultures of human osteoblast-like MG-63 cells. By Northern blot and Western immunoblot analysis, we found, unexpectedly, that PTH (1-34) inhibited MT1-MMP mRNA and protein expression in a dose- and time-dependent manner in MG-63 cells. The PKA antagonist H-89 blunted PTH (1-34)-mediated decreases in MT1-MMP protein synthesis. Forskolin, a PKA agonist, decreased MT1-MMP expression, which was similar to the action of PTH on MT1-MMP expression, in MG-63 cells. Staurosporine, a PKC inhibitor, also blocked the inhibition by PTH. We suggest that both the PKA and PKC pathways are involved in MT1-MMP downregulation by PTH. Furthermore, we found that PTH (1-34) induced the expression of receptor activator of nuclear factor (NF)-B ligand (RANKL) mRNA in a dose- and time-dependent manner in MG-63 cells, and this effect of PTH on RANKL mRNA expression was nearly parallel to the effects of MT1-MMP downregulation, implying a correlation between MT1-MMP and RANKL expression. Our findings suggest that the decreased MT1-MMP expression induced by PTH may be involved in RANKL signaling in osteoblasts, and may play a role in the activation of bone resorption.     

Risk factors for biliary tract and ampullary carcinomas and prophylactic surgery for these factors

Curative resection is the only treatment for biliary tract cancer that achieves long-term survival. However, patients with advanced biliary tract cancer have only a limited prognosis even after radical surgical resection. Thus, to improve the longterm results, the early detection of biliary tract cancer and subsequent cure seem to be essential. The purpose of this study was to review the literature concerning the risk factors for cancerous and precancerous lesions of the biliary tract, and prophylactic surgery for these factors. It has been reported that pancreaticobiliary maljunction (PBM) with bile duct dilatation is a risk factor for gallbladder cancer and bile duct cancer, while PBM without bile duct dilatation is a risk factor for gallbladder cancer. Thus, in the former group, a prophylactic excision of the common bile duct and gallbladder should be recommended, while in the later group, a prophylactic cholecystectomy without bile duct resection may be the appropriate surgical procedure. It has also been reported that primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. Patients with PSC often develop advanced cholangiocarcinoma with a poor prognosis. In patients with PSC, therefore, strict follow-up should be recommended. Adenoma and dysplasia have been regarded as precancerous lesions of gallbladder cancer. A polypoid lesion of the gallbladder that is sessile, has a diameter greater than 10 mm, and /or grows rapidly, is highly likely to be cancerous and should be resected. Although gallstones seem to be closely associated with gallbladder cancer, there is no evidence of a direct causal relationship between gallstones and gallbladder cancer. Thus, a cholecystectomy is not advised for asymptomatic cholecystolithiasis. Controversy remains as to whether adenomyomatosis of the gallbladder and porcelain gallbladder are associated with gallbladder cancer. With respect to ampullary carcinoma, adenoma of the ampulla is considered to be a precancerous lesion. This article discusses the risk factors for cancerous and precancerous lesions of the biliary tract and prophylactic treatment for these factors.     

Regulation of membrane type-1 matrix metalloproteinase activity and intracellular localization in clinical thoracic aortic aneurysms

Objective

Membrane type-1 matrix metalloproteinase (MT1-MMP) is elevated during thoracic aortic aneurysm (TAA) development in mouse models, and plays an important role in the activation of matrix metalloproteinase (MMP)-2 and the release of matrix- bound transforming growth factor-β. In this study, we tested the hypothesis that MT1-MMP is subject to protein kinase C (PKC)–mediated regulation, which alters intracellular trafficking and activity with TAAs.

Recurrence of mucosal carcinoma of the bile duct, with superficial flat spread, 12 years after operation

We report herein a case of recurrent mucosal cancer of the extrahepatic bile duct, with superficial flat spread, 12 years after operation. A 67-year-old woman had undergone common bile duct (CBD) resection and Roux-en-Y reconstruction. Histologically, the tumor was papillary adenocarcinoma, with superficial flat spread, with no invasive component. The epithelium at the distal margin had been exfoliated, so the absence or presence of any remnant cancerous lesion was unclear. But the superficial flat spread had expanded to within at least 3 mm from the distal margin. About 12 years postoperatively, she was hospitalized with upper abdominal pain, and duodenoscopy demonstrated a tumor in the second portion of the duodenum. Biopsy identified adenocarcinoma. Computed tomography showed a low-density mass between the duodenum and pancreatic head. Pancreatoduodenectomy was performed. Histologically, papillary adenocarcinoma was found within the whole of the intrapancreatic bile duct, and its histological appearance resembled that of the original tumor. Moderately differentiated tubular adenocarcinoma had invaded around the tissue of the intrapancreatic CBD. These findings suggest that remnant intramucosal flat carcinoma within the intrapancreatic bile duct had developed into invasive carcinoma over the course of 12 years. This case suggests that remnant intraepithelial flat carcinoma within the CBD may develop a late local recurrence.     

p16抑癌基因在胆管细胞性肝癌中的表达与预后的关系

目的研究ｐ１６抑癌基因与胆管细胞性肝癌发生、发展及预后的关系。方法用免疫组织化学染色ＳＰ法检测胆管细胞性肝癌３８例、癌旁胆管异型增生组织２６例及正常肝内胆管组织中ｐ１６抑癌基因１６例的表达情况。结果ｐ１６抑癌基因在胆管细胞性肝癌组织中表达率为２６％,明显低于癌旁胆管异型增生组织（６９％,Ｐ＜００１）及正常肝内胆管组织（８１％,Ｐ＜００１）;中、低分化胆管细胞性肝癌ｐ１６抑癌基因表达率（１５％）显著低于高分化胆管细胞性肝癌的ｐ１６抑癌基因表达率（５４％,Ｐ＜００５）;在伴有淋巴结转移和门静脉癌栓的病例中,ｐ１６抑癌基因表达率明显低于相应的对照组（Ｐ＜００５）;ｐ１６抑癌基因阳性病人５年生存率为５６％,而ｐ１６抑癌基因阴性病人５年生存率仅为１４％,二者相比差异有显著意义（Ｐ＜００５）;ｐ１６抑癌基因的表达与癌灶体积、癌灶数目及ＨＢｓＡｇ无关。结论ｐ１６抑癌基因的失表达可能在胆管细胞性肝癌的发生发展中起重要作用;ｐ１６抑癌基因表达与胆管细胞性肝癌的分化程度及有无淋巴结转移和门静脉癌栓形成有关,是判定胆管细胞性肝癌恶性程度及估计预后的重要指标之一。     

Differential localization of MT1-MMP in human prostate cancer tissue: role of IGF-1R in MT1-MMP expression

BACKGROUND: MT1-MMP is a metalloproteinase involved in prostate cancer metastasis. The IGF-1R is a tyrosine kinase receptor involved with tumor progression and metastasis. The purpose of this investigation was to examine MT1-MMP and IGF-1R expression and localization in prostate cancer tissues and explore the role of IGF-1R in regulating MT1-MMP in prostate cancer cell lines. METHODS: Immunohistochemistry was utilized to study MT1-MMP and IGF-1R expression in human prostate tissues. IGF-1R regulation of MT1-MMP expression was determined by gene promoter analysis, quantitative RT-PCR and Western blot analysis following pharmacological inhibition of the receptor in PC-3N cells and treatment of LNCaP cells with androgen and IGF-1. RESULTS: MT1-MMP expression was high in the apical regions of the luminal cells in PIN and prostate cancer and less intense in the basalateral regions of benign tissues. IGF-1R was expressed primarily in the basal cells of normal glands and highly expressed in prostate cancer. Inhibition of IGF-1R in PC-3N cells decreased MT1-MMP expression and treatment of LNCaP cells with a synthetic androgen and IGF-1 increased MT1-MMP expression. CONCLUSIONS: These data demonstrate that MT1-MMP is highly expressed in the apical cytoplasmic regions of the luminal cells in PIN and prostate cancer when compared to basalateral cytoplasmic membrane staining in benign glands. Additionally, we demonstrate that IGF-1R is highly expressed in human prostate carcinoma. These findings suggest that MT1-MMP localization and IGF-1R expression in prostate carcinoma could be predictive biomarkers for aggressive disease and support IGF-1R as a promising therapeutic target to decrease processes of prostate cancer metastasis.     

Reappraisal of Hepatopancreatoduodenectomy as a Treatment Modality for Bile Duct and Gallbladder Cancer

Background

Hepatopancreatoduodenectomy has been performed to achieve radical resection in malignant biliary tumors. We reviewed clinical outcomes to evaluate the clinical feasibility of hepatopancreatoduodenectomy for the treatment of gallbladder and bile duct cancer.

Methods

Twenty-three patients underwent hepatopancreatoduodenectomy from 1995 to 2007; 10 gallbladder cancer and 13 bile duct cancer. Median follow-up periods were 15.0 months.

Results

R0 resection was performed in 17 of 23 patients (73.9%). Morbidity and mortality rates were 91.3% and 13.0%, respectively. Five-year survival rates were 10.0% for gallbladder cancer and 32.3% for bile duct cancer. Survival more than 3 years was possible for most patients with stage IIA or less, whereas all gallbladder cancer patients with stage III and all bile duct cancer with stage IIB or more died within 2 years. Bile duct cancer patients with pN0 survived longer than those with pN1 (p?

Conclusions

To obtain negative proximal and distal ductal resection margins in the biliary tract cancer, R0 resection and long-term survival can be achieved by hepatopancreatoduodenectomy. However, its adoption in patients with lymph node metastasis or adjacent organ invasion cannot be recommended.

     

A resected case of a small hepatocellular carcinoma developing within the bile duct

We experienced a resected case of a small hepatocellular carcinoma, which required differential diagnosis from intrahepatic cholangiocellular carcinoma. The patient was a 76-year-old man. While his course had been being observed because of hepatitis C antibody-positive liver cirrhosis, ultrasonographic examination of the abdomen revealed dilation of biliary branches in the anterior segment of the liver and a hyperechoic mass 10mm in diameter at the origin of the branch. A dynamic computed tomography scan showed a high-density tumor in the early phase. After embolization of the right branch of the portal vein, resection of the right lobe of the liver and the extrahepatic bile duct was performed. A resected specimen showed a white-colored mass 8mm in diameter at the origin of the anterior segmental biliary branch. In the pathological findings, the diagnosis was a poorly differentiated hepatocellular carcinoma with strong nuclear atypia; the tumor filled the bile duct, forming a trabecular structure. The immunohistological stains of the tumor were positive for cytokeratin (CK) 8, CK18, and HepParl and negative for alpha-fetoprotein, carcinoembryonic antigen, CA19-9, CK7, CK19, and CK20. There was atypia in the biliary lining epithelium adjacent to the tumor, and the hepatocellular carcinoma may have developed from the biliary epithelium.     

上皮钙黏素1基因启动子甲基化对结肠癌上皮钙黏素和β-连接素表达的影响

目的 探讨上皮钙黏素基因(CDH1)启动子甲基化与结肠癌上皮钙黏素(E-cadherin)及β-连接素(β-catenin)的表达及临床病理特征的关系.方法 采用甲基化特异性PCR技术检测68例结肠腺癌组织、癌旁组织及正常黏膜组织中CDH1基因启动子甲基化的状况.采用免疫组织化学法检测E-cadherin及β-catenin蛋白的表达.结果 癌旁组织及癌组织中CDH1启动子甲基化的阳性表达分别为32.4%(22/68)、57.4%(39/68),正常组织均为阴性表达(P<0.05).E-cadherin在正常组织、癌旁组织及腺癌组织中阳性表达率分别为92.6%、66.2%和44.1%.正常组织中β-catenin均表达于细胞膜上,无胞质和(或)胞核表达,而β-catenin在癌旁组织及癌组织中胞质和(或)胞核表达分别为29.4%和50.0%.CDH1基因启动子甲基化阳性率与E-cadherin表达则呈负相关(r=-0.312,P=0.01),与β-catenin胞质和(或)胞核表达呈正相关(r=0.309,P=0.018).CDH1基因启动子甲基化及E-cadherin、β-catenin的异常表达均与结肠癌分化程度及转移密切相关(P<0.05).结论 CDH1基因启动子甲基化可能是导致结肠癌E-cadherin与β-catenin异常表达及肿瘤侵袭性增强的重要原因.

Abstract：

Objective To investigate the relationship between methylation of the CDH1 gene promoter on the expression of E-cadherin and β-catenin, and to evaluate the correlation with clinicopathological characteristics of the colonic carcinoma. Methods Methylation specific PCR (MSP) was used to detect CDH1 gene promoter methylation in the cancer tissue, adjacent tissues and normal tissues in 68 patients. The expression of E-cadherin and β-catenin was determined by immunohistochemistry staining. Results The positive rate of CDH1 gene promoter methylation was 32.4% in adjacent tissues and 57.4% in cancer tissue, while no detectable methylation was found in all the normal tissues. The difference was statistically significant. The positive rate of E-cadherin was 92.6% in the normal tissues, 66.2% in the adjacent tissues and 44.1% in the cancer tissues. In all normal tissues, β-catenin was expressed only at the cellular membrane but not in the cytosol or nucleus, while the expression of β-catenin was present in the cytosol or nucleus in 29.4% of the adjacent tissues and 50.0% of the cancer tissues. The positive rate of CDH1 gene promoter methylation was negatively correlated with E-cadherin expression (r =-0.312,P =0.01) and positively correlated with β-catenin cytosolic/nucleus expression(r=0.309,P=0.018). The differentiation and metastasis of colonic carcinoma were associated with the aberrant expression of E-cadherin, β-catenin, and methylation of CDH1 promoter (P<0.05). Conclusion CDH1 gene promoter methylation may lead to aberrant expression of E-cadherin and β-catenin in colonic carcinoma, and may play an important role in promoting the invasion of tumor.     

High Grade Dysplasia: Surveillance,Mucosal Ablation,or Resection?

Barretts esophagus is a common premalignant condition that results from chronic gastroesophageal reflux. High grade dysplasia in the metaplastic esophagus is thought to be the last step in the metaplasia-to-carcinoma sequence that characterizes this disease. The management of high grade dysplasia in Barretts esophagus is controversial. Some investigators advocate a rigorous endoscopic surveillance program with biopsies, but this approach has been questioned because of its clinical impracticality, high cost, possibility of sampling errors, and difficulty demonstrating effectiveness on a reproducible basis. Others advocate mucosal ablative therapy to eradicate the dysplastic and metaplastic epithelium. This approach, still in its infancy, cannot be accepted as standard therapy at the present time because of limited follow-up, its questionable ability to completely eradicate the abnormal mucosa, the phenomenon of pseudoregression, and the patients require continued rigorous endoscopic surveillance. Esophagectomy, on the other hand, can be accomplished with a low mortality rate in these patients. We advocate this approach because a large number of them have invasive cancer in the esophagus despite a preoperative diagnosis of only high grade dysplasia. In addition, the 5-year survival is excellent even if invasive cancer is present, and these patients are liberated from rigorous endoscopic surveillance for the rest of their lives. For patients with high grade dysplasia in Barretts esophagus who are poor operative risks, less invasive approaches such as mucosal ablation may play a role, but longer follow-up information is needed before this technique can be accepted even in this setting.     

Anatomic and molecular pathology of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor of the liver, and ICC is reportedly increasing recently. ICC is usually adenocarcinoma with variable desmoplastic reaction, although there are several special or unusual histological features. ICC may arise at the large intrahepatic bile duct near the hepatic hilus and also from the bile ductules at the border of the hepatic parenchyma. On the anatomical level, the pathology of ICC differs depending on the region from which the ICC arises. At the large intrahepatic bile duct, ICC presents papillary growth and periductal infiltration. Some cases show extensive papillary growth and intraluminal spread with marked gastroenteric metaplasia. Mucus core protein 1 is expressed in aggressive ICC. ICC arising from ductules shares phenotypes of hepatocellular carcinoma. ICC in chronic biliary diseases, particularly arising in hepatolithiasis, presents precancerous lesions that include biliary epithelial dysplasia, as well as in-situ carcinoma. Chronic advanced hepatitis C is one of the background diseases of ICC. Chronic inflammation, with the upregulation of cyclooxygenase-2 and growth factors, and the formation of reactive oxygen species are one of the causative factors in the DNA damage of biliary epithelial cells. K-ras mutation and aberrant expression of p53 are found in one-third of ICCs. The latter may be due to mdm-2 upregulation. Hepatocyte growth factor/met and interleukin 6 (IL6)/IL6 receptor are involved in cell proliferation/mitoinhibition and apoptosis in ICC. Fibrous stroma formation and invasion involve the proliferation of -smooth muscle antigen-positive stromal cells, and cell-to-cell and cell-to-matrix interactions involving E-cadherin/catenin and CD44 and matrix proteinases may be involved in the invasion of ICC. Evasion of immune surveillance involving the Fas/FasL system is important in the malignant progression of ICC. Further molecular and genetic studies are mandatory to evaluate the pathogenesis and progression of ICC.     

Bile duct complications after laparoscopic cholecystectomy

Summary A retrospective review and analysis of patients referred to the Division of Gastroenterology and the Section of Gastrointestinal Surgery with common bile duct complications after laparoscopic cholecystectomy was undertaken in order to identify injury patterns, management, and outcome. Sixteen patients were identified over a 20-month period. Twelve patients had major common bile duct injuries and four had minor injuries (cystic duct leaks). Seventy-one percent of injuries occurred with surgeons who had done more than 13 laparoscopic cholecystectomies. Eighty-three percent of patients who had major ductal injury did not have a cholangiogram prior to the injury. Sixteen percent of patients with major common bile duct injuries had findings of acute cholecystitis and 58% of these major injuries were easy gallbladders. One-third of major injuries were recognized at operation. Two-thirds of immediate repairs failed. All cystic duct leaks were managed nonoperatively.It appears that bile duct complications after laparoscopic cholecystectomy are more common in the community than is reported. Bile duct complications occur with surgeons who are experienced and inexperienced with laparoscopic cholecystectomy. Common bile duct injuries, unrecognized at laparoscopic cholecystectomy in the majority of cases, usually occur with easy gallbladders. Operative cholangiography is not utilized in the majority of common bile duct injuries. When immediate repair of common bile duct injuries is undertaken, the majority are unsuccessful. Endoscopic retrograde cholangiopancreatography (ERCP) is invaluable in the diagnosis and management of bile duct complications. Cystic duct leaks may be managed successfully with endoscopic stents.Presented at the annual SAGES meeting, April 10–12, 1992, Washington, D.C.