Well-differentiated adenocarcinoma, gastric foveolar type, of the extrahepatic bile ducts: A previously unrecognized and distinctive morphologic variant of bile duct carcinoma

Two examples of a rare but distinctive morphologic variant of extremely well-differentiated adenocarcinoma of the extrahepatic bile ducts are reported. One tumor arose in the common bile duct of a 51-year-old man; the other arose in the common hepatic duct of a 27-year-old man. Both tumors were composed predominantly (>95%) of gastric foveolar-type epithelium. Because of their bland nuclear features, low mitotic index, and focal polypoid and lobular architecture, they were initially confused with adenomas. Foci of less-differentiated adenocarcinoma and perineural invasion present in the deep portions of the tumors facilitated recognition. The neoplastic cells and extracellular mucin were periodic acid-Schiff- and alcian blue-positive. By immunohistochemistry, the tumor cells expressed cytokeratins 8 and 20 as well as cathepsin D, as reported in normal foveolar cells. Likewise, p53 overexpression was documented immunohistochemically in both adenocarcinomas, which also stained with the Ki-67 antibody. Despite the well-differentiated nature of the neoplasms and their deceptively benign microscopic appearance, one patient developed recurrence and liver metastasis 5 years after surgery. The other patient is disease-free 2 years following a segmental resection of the common hepatic duct, cystic duct, and gallbladder. The cell phenotype of these tumors can be explained by the ability of the bile duct epithelium to differentiate along gastric cell lines.     

Biliary reconstruction with right hepatic lobectomy due to delayed management of laparoscopic bile duct injuries: a case report

We report a case requiring biliary reconstruction with right hepatic lobectomy due to biliary strictures caused by continuous cholangitis after laparoscopic bile duct injury. The patient, a 55-year-old woman, underwent laparoscopic cholecystectomy for cholelithiasis at another hospital. Although a bile leakage from the intraabdominal drain was observed several days after the operation, the patient was not given adequate treatment to stop the leakage. Two months after the initial laparoscopic cholecystectomy, she was referred to our hospital. Endoscopic retrograde cholangiopancreatography (ERCP) showed complete obstruction of the common hepatic duct, which was caused by clipping during laparoscopic cholecystectomy. Cholangiography from percutaneous transhepatic biliary drainage (PTBD) catheters revealed that sections of the secondary branches of the right intrahepatic bile duct had become constricted due to persistent cholangitis. Fortunately, the left hepatic duct was judged to be normal by imaging. Therefore, we elected to perform a right hepatic lobectomy and left hepaticojejunostomy, because we felt that performing a hepaticojejunostomy without hepatic resection would put the patient at risk of continuing to suffer from cholangitis. The patient was discharged on the 55 th postoperative day, and, 5 years after reconstructive surgery, is healthy and has remained free from biliary strictures in the remnant liver. Appropriate decision-making is essential in the treatment of biliary injury after laparoscopic cholecystectomy. Surgeons should not hesitate to perform biliary reconstruction with hepatic resection to reduce the risk of cholangitis or biliary strictures of the remnant liver. More importantly, preoperative clear imaging of the biliary tree and suitable management of any biliary injury which might occur are necessary to avoid having to perform reconstructive surgery.     

Liver metastasis from rectal cancer with prominent intrabile duct growth

Intrabiliary growth of liver metastases from colorectal cancer has rarely been studied. A surgically resected case of a metastatic liver tumor with prominent intrabiliary growth derived from rectal cancer is reported. The patient was a 62-year-old man who had received a low anterior resection for rectal cancer in March 2000. He was re-admitted due to obstructive jaundice in January 2003, and was diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary tumor extending from the intrahepatic bile duct of segment II to the common hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI, and an extrahepatic bile duct resection with reconstruction of the biliary tract. In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in diameter in segments II and VI, respectively, and an intrabiliary tumor originating from the main tumor in segment II extended to the common hepatic duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to moderately differentiated adenocarcinoma, which showed the same histological features as the rectal cancer. The immunohistochemical findings strongly supported that these tumors, including the intrabiliary growth, were liver metastasis from the rectal cancer. The intrabiliary invasion and growth of metastatic liver tumors has generally been overlooked, notwithstanding their frequently observed biological behavior. The present case is informative, and further investigation into this type of metastatic liver tumor may be warranted.     

胆管神经内分泌癌的诊断和治疗

目的 提高对胆管神经内分泌肿瘤的认识。方法 报道国内首例肝总管神经内分泌癌合并肝脏转移，结合国内已经报道的8例未发生转移病例，总结该病的诊断和治疗。结果 男性3例，女性6例，8例以梗阻性黄疸起病，2例合并类癌综合征，梗阻部位胆总管下段2例，肝总管6例，胆总管中段1例，手术前均未能确诊；采取探查性手术，5例行根治性切除胆管空肠吻合术，2例行Whipple手术，1例行姑息切除＋肝动脉插管化疗，1例外引流，手术后病理确诊。结论 胆管神经内分泌癌是一种少见的胆道恶性肿瘤，梗阻性黄疸是常见的症状，NSE、Cg-A、SYP等免疫组化染色是诊断的要点；手术切除率高，根治性切除是治疗的首选，如果肿瘤转移，姑息性切除＋肝动脉化疗是比较好的选择。     

Hilar cholangiocarcinoma with extensive immunoglobulin G4 reaction

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that can involve multiple organs. It is often challenging to distinguish IgG4-related sclerosing cholangitis (IgG4-SC) from cholangiocarcinoma because of overlap in their clinical findings. A 75-year-old man presented to a hospital for a detailed examination of the elevation of some biliary enzymes. Radiographic examination revealed segmental bile duct with wall thickening of the common hepatic bile duct, and dilation of the peripheral branches. Transampullary biopsy showed a non-specific inflammatory reaction with several IgG4-positive cell infiltrations. There were no signs of malignancy. The liver biopsy showed bile duct injury accompanied by IgG4-positive cell infiltration. We then performed bile duct biopsy and finally diagnosed the patient with cholangiocarcinoma. We should remember that the IgG4 reaction is neither completely sensitive nor specific for IgG4-RD and avoid resting solely on the IgG4 reaction to precisely distinguish IgG4-SC from cholangiocarcinoma.     

亚毫米CT观察肝外胆管的供血小动脉*

背景：亚毫米CT扫描速度极快,有效减少了运动伪影,分辨力极高,可以观察到内径在1 mm以下的小动脉。 目的：采用亚毫米CT观察肝外胆管的供血小动脉。 方法：纳入因各种原因需行上腹部亚毫米CT血管造影患者54例,利用连续薄层源图像观察,辅以多平面重组、最大密度投影、容积再现,观察小动脉起源、支数、分布优势,同时测量胆总管直径。 结果与结论：54例图像中胆总管均为1支,走行无特殊,其中51例能观察到胰十二指肠上动脉,伴行于胆总管下段;其中7例胰十二指肠上动脉与胰十二指肠下动脉吻合成动脉弓,亦伴行下段胆总管;上段供血小动脉中11例为胆囊动脉近段,14例发自右肝动脉,2例发自肝固有动脉,1例发自肝总动脉,1例发自左肝动脉。下段胆管供血小动脉占优势者39例,上段供血小动脉占优势者10例,其余5例较为均衡。54例胆总管内径4-24(11.0±5.8) mm。表明胆总管上段供血脆弱,因此该区术中不宜盲目分离、结扎小血管;对于胆石症与肝胰良恶性占位的中老年患者,术前行上腹部CT血管造影检查是有必要的。关键词：胆总管;动脉;血供;计算机断层成像(CT);血管造影 doi:10.3969/j.issn.1673-8225.2012.18.017     

Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat.

The reversibility of hepatic fibrosis was investigated in an experimental model of extrahepatic cholestasis in the rat after common bile duct ligation for 2 weeks, followed by bilioduodenal anastomosis for 3 weeks. Bile duct ligation resulted in a transitory marked elevation in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin during the first 3 days. Then these levels decreased to threefold, twofold, and 100-fold the normal values, respectively, during the following 4 weeks. Histologic examination of the liver disclosed extensive bile duct proliferation and the formation of periportal fibrosis, with only slight inflammation and necrosis. The distribution of the major components of the hepatic extracellular matrix was analyzed 2 weeks after bile duct ligation, using the indirect immunoperoxidase method. Fibrous septa were found to be strongly stained for collagens I, pro-III, III and IV, fibronectin, and laminin. The most intense staining was found in enlarged periportal areas, collagen IV and laminin being particularly abundant around newly formed bile ducts. These changes paralleled high steady-state levels of alpha 1(I) and alpha 1(IV) collagen and B2 chain laminin mRNAs. Relief of the obstruction for 2 weeks resulted in a shift in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin toward normal values. A dramatic resorption of bile duct proliferations and periportal fibrosis were observed. Three weeks after bile duct repermeabilization, immunohistochemical study showed that the pattern of distribution of extracellular matrix components was almost normal, except for collagen IV, which remained abundant in the sinusoids when compared with the normal liver. In parallel, the steady-state B2-chain laminin mRNA level became lower than in cholestatic livers, whereas alpha 1(I) and alpha 1(IV) mRNAs were almost undetectable. These results show that hepatic fibrosis induced by experimental extrahepatic cholestasis in rat disappears in less than 3 weeks after relief of bile duct obstruction, suggesting that an active degradation of matrix protein occurs, except for collagen IV in the sinusoid.     

Factors producing bile infarction and bile duct proliferation in biliary obstruction

To clarify the factors producing bile infarction and bile duct proliferation in obstructive jaundice, the incidence of the hepatic lesions and the serum levels of the bile constituents were examined in three rat models. (1) Ligation of the common bile duct induced bile infarction, bile duct proliferation, retention of bile in the liver, and elevation of the serum levels of total bilirubin and total bile acids. (2) The rats treated by choledochotomy had bile in the abdominal cavity, but there was no retention of bile in the liver. The degree of development of bile infarction was similar to that of the common bile duct ligation group, but bile duct proliferation was not found: the serum levels of total bilirubin and total bile acids were elevated. (3) In the rats subjected to partial bile duct ligation, bile infarction and bile duct proliferation were seen only in the lobes with ligation of the hepatic ducts: only slight or no elevation of the serum levels of total bilirubin and total bile acids was found. These data suggest that bile infarction is caused by the toxic action of bile constituents other than bilirubin and bile acids, absorbed into the blood from the obstructed biliary system, and that bile duct proliferation is due to mechanical factors following bile retention or direct actions of retained bile in the liver.     

Biomechanical study of the bile duct system outside the liver.

Diseases of the bile duct system in the digestive system after surgery are common. In order to clarify the cause of these diseases, research on the diseases from a biomechanical perspective is increasing; however, the same cannot be said of biochemical research. In this paper, by using a new, well-devised testing apparatus, specimens extracted from the bile duct system of canine body are tested. The test data are analyzed using the finite deformation theory, and mechanical properties of the bile duct system outside the liver are investigated. The conclusions show that the viscoelasticity of the bile duct system is very small. In its normal physiological condition, the bile duct wall has an almost uniform distribution of circumferential and longitudinal stress. However, when the diseases of the bile duct system cause high pressure at the bile duct, the circumferential stress and longitudinal stress at the bile inside wall suddenly increase and are much larger than those stresses at the outside wall. The elastic modulus gradually becomes small from the common bile duct and the common hepatic duct to hepatic duct, and the value of elastic modulus for the cystic duct is almost equal to that of the hepatic duct.     

Anatomie und Pathologie des intrahepatischen und extrahepatischen Gallengangskarzinoms

Adenocarcinomas of the intra- and extrahepatic bile ducts are rare tumors that begin with malignant transformation of the bile duct epithelia. Intrahepatic cholangiocarcinomas derive from the small bile ducts located proximally to the right and left hepatic ducts. Extrahepatic bile duct carcinomas originate in the right or left hepatic duct, the cystic duct, or the choledochal duct. Tumors located at the bifurcation are called Klatskin tumors. The intrahepatic cholangiocarcinomas are classified according to the TNM classification of liver tumors, while the extrahepatic bile duct tumors have their own TNM classification. Several factors, accompanied by a chronic inflammatory reaction, have been discussed in the etiopathogenesis of these tumors: schistosomiasis, ulcerative colitis with primary sclerosing cholangitis, and inborn bile duct cysts of the liver as a consequence of a disturbance of the ductal plate formation. Over 95% of bile duct tumors are adenocarcinomas. In the nomenclature of precursor lesions a two-grade classification of dysplasia (low-grade versus high-grade) has been found to be more reproducible.     

Endocrine cell carcinoma of extrahepatic bile duct

An endocrine cell carcinoma of the extrahepatic bile duct in a 79-year-old man is described. The patient had complaints of jaundice and epigastric pain due to a small tumor located at the confluence of the common hepatic duct with the cystic duct. Microscopically, the tumor showed a well differentiated tubular adenocarcinoma and was confined to the mucosa. Numerous tumor cells showed argyrophil and/or argentaffin reactions. Immunoperoxidase staining revealed that the tumor tissue contained somatostatin-, gastrin-and serotonin-immunoreactive cells. From these findings the tumor was diagnosed as endocrine cell carcinoma. Four years later he remains well without any evidence of recurrence or metastasis. The histogenesis of endocrine cells in the biliary tract is briefly discussed.     

急性胆源性胰腺炎的个体化治疗分析

目的 探讨急性胆源性胰腺炎（ABP）临床个体化治疗方法及效果。方法 回顾性分析34 例ABP患者的临床资料。其中原发病为胆囊结石18例,胆总管结石7例,胆囊结石合并胆总管结石 5 例,未见胆囊及胆管结石但有胆总管扩张表现 4例;轻型急性胰腺炎11 例,重症急性胰腺炎23例。34例均在采用保守治疗的同时实施早期微创治疗,其中经皮肝穿刺胆管引流术（PTCD）15例;胆囊穿刺引流术10例;经内镜逆行胰胆管造影术（ERCP）4例;经皮穿刺胰周引流术＋胆囊穿刺1例,经皮穿刺胰周引流术＋PTCD 4例,其中3例（8.82%）经上述治疗后无缓解施行急诊手术（胆囊切除＋胆总管切开取石＋T管引流术＋胰腺坏死组织清除术＋胰周引流术1例,以及加腹腔减压术2例）。结果 3例急诊手术患者中,2例治愈出院后无ABP再次发作,1例死亡;26例（76.47%）择期手术（胆囊切除术22例、胆囊切除＋胆总管切开＋T管引流术 4例）,随访期间,无ABP再次发作;4例（ 11.76%）患者暂未行手术治疗,随访期间4例中均无ABP再次发作;1例患者微创介入治疗（PTCD）后,住院期间死亡未行手术治疗。全组并发心功能损害15 例（44.12%）,肾功能损害 11 例（32.35%）,肝损害 12例（35.29%）,急性肺部感染9例（26.47%）。治愈32例（94.12%）,死亡2例（5.88%）。结论 对于ABP的治疗应按不同病因和病期采取个体化治疗方案,早期ERCP、超声引导下经皮经肝胆管或胆囊穿刺引流或胰周引流能显著提高疗效。     

Fibrolamellar carcinoma as a cause of bile duct obstruction

Obstructive jaundice due to growth within bile ducts of hepatocellular carcinoma is uncommon and usually a manifestation of advanced, lethal tumour. We report a case of fibrolamellar carcinoma of the liver presenting with obstructive jaundice, caused by tumorous permeation of the left hepatic duct with migration of tumour fragments into the common bile duct. Immunocytochemical and ultrastructural features are described. Two and a half years after complete surgical resection the patient is free of tumour. The importance of accurate diagnosis of such tumours is emphasized.     

活体造影法肝内胆管的解剖学研究及临床意义

目的　通过经皮胆道直接造影,研究肝内胆管的解剖与变异的类型与分布。 方法　经皮胆道造影50例, 用20 ml注射器接体外引流管进行造影,胆管充分显影的状态下,旋转拍摄胆管,观察胆管解剖与变异。 结果　50例成像中胆管变异42.0％（21例）。12.0% (6例)显示右前叶肝管、右后叶肝管及肝左管呈三分叉状汇合形成肝总管。8.0% (4例) 肝左管先和右前叶肝管汇合,在肝门处与右后叶肝管汇合。20.0% (10例) 肝左管先和右后叶肝管汇合,在肝门处与右前叶肝管汇合。2.0% (1例)多个肝管在肝门处汇合。 结论　胆管解剖与变异的分析对术前手术方式的确定有一定的临床意义。     

Composite large cell neuroendocrine carcinoma and adenocarcinoma of the common bile duct

Large cell neuroendocrine carcinoma (LCNEC) is a high grade type of neuroendocrine tumour with an aggressive clinical course. This report describes the first case of LCNEC combined with an adenocarcinoma component in the common bile duct. A 68 year old man presented with jaundice. Severe stenosis of the bile duct was revealed by endoscopic retrograde cholangiography, and adenocarcinoma cells were detected by brush cytology. Pancreaticoduodenectomy was performed, and the patient died of disease three months after surgery. A tumour measuring 2.0 cm in diameter was located in the intrapancreatic portion of the bile duct. Histologically, the tumour consisted of a LCNEC component and a well differentiated adenocarcinoma component. There were transitional areas between the two components. Immunohistochemically, LCNEC cells were reactive for neuroendocrine markers, but no specific hormonal expression was found. Chromogranin A positive cells were found in some areas of the adenocarcinoma component. These findings are consistent with the theory that both of the carcinoma components originated from a common pluripotent stem cell.     

ENDOCRINE CELL CARCINOMA OF EXTRAHEPATIC BILE DUCT

An endocrine cell carcinoma of the extrahepatic bile duct in a 79-year-old man is described. The patient had complaints of jaundice and epigastric pain due to a small tumor located at the confluence of the common hepatic duct with the cystic duct. Microscopically, the tumor showed a well differentiated tubular adenocarcinoma and was confined to the mucosa. Numerous tumor cells showed argyrophil and/or argentaffin reactions. Immunoperoxidase staining revealed that the tumor tissue contained somatostatin-, gaastrin-and serotonin- immunoreactive cells. From these findings the tumor was diagnosed as endocrine cell carcinoma. Four years later he remains well without any evidence of recurrence or metastasis. The histogenesis of endocrine cells in the biliary tract is briefly discussed.     

Two cases of common bile duct stone after liver transplantation

Biliary complications after orthotopic liver transplants are a continuing cause of morbidity and mortality. Biliary stones and sludge are less well known complications of hepatic transplantation, although they have long been recognized. Recently we experienced two cases of biliary stones developed after liver transplantation. One 32-year-old male, who frequently admitted due to recurrent cholangitis, was treated with percutaneous transhepatic biliary drainage and choledochojejunostomy with cholecystectomy. The other 58-year-old male, who had stones in commone bile duct, was treated by endoscopic manipulation. They are in good condition without recurrent bile duct stones or its accompanying complications. Although stones and sludge are relatively infrequent after liver transplantation, surgical or interventional radiologic treatments are usually performed for treatment.     

Tissue polypeptide antigen--a marker antigen differentiating cholangiolar tumors from other hepatic tumors

Twenty-two cases of primary hepatic tumors consisting of 11 hepatocellular carcinomas, 6 cholangiocarcinomas, 3 mixed hepatocellular and cholangiocellular carcinomas, and 2 biliary cystadenocarcinomas together with 8 cases of metastatic adenocarcinoma from various sites were studied by immunoperoxidase technic to demonstrate tissue polypeptide antigen. All of the tumors presumably derived from the epithelial lining of the bile duct, including cholangiocarcinoma, cholangiocarcinomatous portion of the mixed hepatocellular and cholangiocellular carcinoma, and biliary cystadenocarcinoma showed strong positive reaction. The hepatocellular carcinoma and the metastatic adenocarcinoma exhibited negative to weakly positive reactions. These results indicate that TPA can be of use in differentiating bile duct carcinomas from hepatocellular carcinoma and, to a lesser extent, from hepatic metastases of various adenocarcinomas.     

Primary follicular lymphoma of the extrahepatic bile duct mimicking a hilar cholangiocarcinoma: case report and review of the literature

We report a case of a 53-year-old Asian woman who presented with abdominal pain, bloating, dysphagia, and signs of incomplete biliary obstruction, having elevated liver function tests but without increased bilirubin. Imaging studies revealed a mass measuring 6.0 × 8.0 cm at the porta hepatis extending to the right lobe of the liver and obstructing the common hepatic duct, causing mild to moderate intrahepatic biliary dilation and variable occlusion of the right portal vein. At laparotomy, an infiltrative neoplasm was noted at the hilum that involved the common bile duct, right and left hepatic ducts, and the right lobe of the liver. Extended right hepatectomy and resection of the extrahepatic bile duct and right portal vein was performed. Histologic examination revealed a high grade follicular lymphoma (grade 3A) with a predominantly follicular pattern of growth. Portal lymph nodes and a staging bone marrow biopsy showed no evidence of lymphoma. The patient subsequently received chemotherapy. Postoperative follow-up of more than 4 years has been uneventful, without disease recurrence. To the best of our knowledge, this is the third report of a primary extranodal follicular lymphoma of the extrahepatic biliary system.