Intrahepatic biliary cysts in congenital biliary atresia

A case of pronounced cystic dilatation of the intrahepatic bile ducts with biliary atresia is presented. Intrahepatic biliary cysts have been described in biliary atresia, although, as far as we are aware, none as extensive as in this case. The cysts represent end-stage obstruction with irreversible liver injury; thus, drainage of these cysts does not alleviate the condition. The differential diagnosis includes Caroli's disease, congenital hepatic fibrosis, and polycystic liver disease.     

Extrahepatic biliary atresia. Morphological study of 98 biliary remnants

Histologic examination was performed on 98 biliary remnants. Classification into three types was made according to the presence of epithelial structure; biliary and glandular formations had to be separated. Atretic lesions were predominantly observed at the pars inferior of the remnants. These histological findings agree with the theory of a dynamic ascending process that leads to progressive, complete destruction of the biliary and glandular structure, although main ducts may remain preserved by the vicinity of the porta hepatis. Classic clinical data suggest that the damage is initiated in utero. The lesions certainly progress after birth; in some cases the fibrotic process of the remnant may have already reached completion at birth, whereas in some others it may become clinically evident after birth.     

术前胆道引流对肝胆管结石合并胆汁性肝硬化的作用

目的探讨肝胆管结石合并继发性胆汁性肝硬化病人，在进行肝叶切除手术前行胆道引流（PBD）的作用。方法回顾性分析67例行肝叶切除治疗合并继发性胆汁性肝硬化的肝胆管结石病例，其中PBD组35例均行术前胆道引流，非PBD组32例未行术前胆道引流，将两组的肝功能变化、结石清除率、并发症发生情况等进行比较分析。结果PBD组的术前肝功能较入院前有所改善，术中结石清除率高于非PBD组，两组的手术并发症发生情况无显著差异。结论术前胆道引流虽然没有减少手术并发症，但可以改善术前肝功能，增加结石清除率。     

Intrahepatic biliary papillomatosis

A 66-year-old man had intrahepatic biliary papillomatosis. This benign tumor has great growth potential that can present a difficult management problem.     

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.     

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease, which is invariably fatal. Circumstantial and indirect evidence suggests that autoimmune mechanisms have a role in the pathogenesis of PBC. Antimitochondrial antibodies (AMA) are highly sensitive and specific markers that can predict the development of the disease in a healthy individual. Long-term administration of ursodeoxycholic acid (UDCA), a naturally occurring bile acid, safely slows the progression of PBC, delays the need for liver transplantation, and postpones death. An effort should be made to identify the patients with PBC in the asymptomatic stage by the presence of AMA and to conduct a clinical trial in order to assess the benefit of long-term administration of UDCA on the prevention of the overt disease in these individuals.     

Primary biliary cirrhosis

Primary biliary cirrhosis is an autoimmune chronic cholestatic liver disease of unknown cause that usually affects middle-aged women. It is characterized by inflammatory destruction of the interlobular and septal bile ducts, which leads to chronic cholestasis and cirrhosis. The diagnosis should be considered in the setting of elevated alkaline phosphatase, immunoglobulin M level and the presence of antimitochondrial antibody in serum. Ursodeoxycholic acid is the only medication of proven benefit for these patients. Liver transplantation is only therapeutic option for patients who have end-stage disease.     

Primary biliary cirrhosis

There are many unresolved issues in PBC that should be the focus of investigation, but studies are hampered by the general unhelpfulness of the experimental systems. There is no satisfactory animal model for this illness, perhaps owing to the fact that the physiology of the biliary systems of many common laboratory animals differ significantly from that of humans. Secondly, the relative rarity of the disease means that we almost never come across it in the early or preclinical stage. Perhaps it is now time to design large-scale prospective surveys so that we can obtain samples from patients that can be retrospectively examined once they develop the disease. This could shed light on many immunological phenomena that we can only now examine during late-stage disease.     

Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm

Cholangiocarcinoma of intrahepatic and extrahepatic bile ducts has a multistep carcinogenesis. Two premalignant lesions have been suggested for invasive cholangiocarcinoma: biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. How the carcinogenetic process differs between biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct is not clear. In this study, we performed a pathological study to reveal the expression of key molecules related to the cell cycle during 2 carcinogenetic lineages. We immunohistochemically examined the expression of p21, p53, cyclin D1, and Dpc4 in a total of 89 cases: nonneoplastic biliary epithelium, biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and invasive cholangiocarcinoma. The expression of p21, p53, and cyclin D1 was up-regulated with histological progression in both biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct, whereas Dpc4 expression was down-regulated in these 2 lineages. In biliary intraepithelial neoplasia, p21 expression was significantly up-regulated early on. In contrast, levels of all molecules changed gradually in intraductal papillary neoplasm of the bile duct. Changes in p53 expression during histological progression differed significantly between biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. p53 expression was dramatically up-regulated at the invasive stage of biliary intraepithelial neoplasia, whereas it was quite low in noninvasive biliary intraepithelial neoplasia. In contrast, p53 expression was already up-regulated in low-grade intraductal papillary neoplasm and reached a plateau in high-grade intraductal papillary neoplasm and invasive cholangiocarcinoma. This study suggested p21, p53, cyclin D1, and Dpc4 to be involved in the carcinogenesis of both biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. p53 expression was regulated differently in biliary intraepithelial neoplasia compared with intraductal papillary neoplasm of the bile duct.     

A case of unclassified multicystic biliary tumor with biliary adenofibroma features

A 40-year-old Japanese man was admitted to our hospital for evaluation of upper abdominal pain. Abdominal computed tomography (CT) revealed a well-circumscribed multicystic mass measuring approximately 7 × 6 cm. The mass contained a solid lesion measuring 3 × 2 cm. Biopsy of a swollen cervical lymph node led to a diagnosis of diffuse large B-cell lymphoma. After initial chemotherapy for lymphoma, the multicystic mass was surgically resected. The tumor was composed of a multicystic lesion and a solid lesion. Histopathologic examination of the multicystic lesion revealed that the locules were lined by biliary epithelium, demonstrating various degrees of cytological atypia. The stroma was fibrous, and the tumor showed marked apocrine snouts. Part of the tumor showed papillary growth with strong cytological atypia. The solid lesion showed tubulocystic proliferation of tumor cells, with prominent apocrine snouts, embedded in dense and partially hyalinized fibrous stroma. The morphology of the solid part was quite similar to that of reported biliary adenofibroma. Despite lengthy discussion, an appropriate pathological diagnosis could not be found among the current classifications of biliary tumor. The tumor was finally diagnosed as unclassified multicystic biliary tumor with adenofibroma features.