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.     

Anaerobes in human biliary tracts.

During a 2-year period, 1,892 patients underwent biliary tract surgery at the Mayo Clinic. Both aerobic and anaerobic cultures of bile were performed in 371 of these patients. Sixty-nine percent of the cultures were positive, and 41% (117) of these grew anaerobes, although they were present in pure culture only twice. Mixed cultures most commonly contained four different organisms (three aerobes and one anaerobe). Bacteroides fragilis was the single most commonly isolated anaerobe and ranked fourth in terms of overall isolates behind Escherichia coli, group D streptococci, and Klebsiella B. fragilis accounted for 7.0% of the total group D streptococci, and Klebsiella. B. fragilis accounted for 7.0% of the total aerobic and anaerobic isolates and was present in 21% of all positive cultures. Pseudomonas aeruginosa and Clostridium perfringens ranked fifth and sixth, providing 6.5 and 5.9% of all isolates, respectively. This study demonstrates the frequent presence of anaerobes in patients with bactibilia and suggests that they be considered in the formulation of antimicrobial therapy for infections involving human biliary tracts.     

Primary biliary cirrhosis and autoantibodies.

Fifty years have passed since anti-mitochondrial antibodies were found in patients with primary biliary cirrhosis (PBC). PBC is an autoimmune hepatic disease in which 85-90% of patient antibodies bind to mitochondrial antigens that include pyruvate dehydrogenase complex (PDC)-E2 and other members of the oxaloacid dehydrogenase family. In addition, indirect immunofluorescence (IIF) assays utilizing HEp-2 cell substrates have been used to identify anti-centromere antibodies in 20-30% of PBC sera. These antibodies are generally easily recognized, however, anti-nuclear envelope and anti-multiple nuclear dot antibodies are occasionally more difficult to recognize with certainty by IIF. The use of enzyme linked immunosorbent assays that utilize recombinant gp210 (an autoantigen of the nuclear envelope) and/or sp100 (a protein target represented by multiple nuclear dots) should be particularly considered in anti-mitochondrial antibody negative PBC sera. Although the clinical significance of these antibodies still remains to be determined, there is evidence that the existence of anti-gp210 antibodies are related to poorer prognosis and more aggressive disease progression.     

Identification of biliary antigens in circulating immune complexes in primary biliary cirrhosis.

The presence of biliary tract antigens in circulating immune complexes from patients with primary biliary cirrhosis (PBC) was investigated. Concentrations of immune complexes in PBC sera, measured by the Raji cell immunoassay, ranged from 58 to greater than 1,000 microgram/ml, but did not correlate with disease activity. Immunofluorescent staining of complexes bound to Raji cells was carried out with guinea-pig antiserum raised against biliary tract antigens. Positive staining reactions were observed with complexes obtained from PBC patients, but not with those obtained from patients with systemic lupus erythematosus or rheumatoid arthritis, indicating that in PBC antigenic components associated with the biliary tract are contained within the complexes.     

Familial primary biliary cirrhosis in Hiroshima.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitochondrial antibodies and chronic inflammatory destruction of septal and intrahepatic bile ducts. Although there are no obvious associations of PBC with MHC class I or class II genes, there appears to be a significant increased risk of developing disease within families. Clearly, a combination of genetic and environmental factors play a role in disease pathogenesis, although the relative contributions of each are unclear. In this study, we have taken advantage of the well-defined health-care system in Hiroshima prefecture, where PBC is a reportable disease. In the period 1988-1997, 156 new patients with PBC in a total population of 2,873,000 were diagnosed. These patients included 18 subjects that were derived from eight different families in which more than one family member had a history of PBC; this reflects a frequency of 5.1% and further shows that the prevalence of PBC is greatly increased in family members. Of interest, the median age of onset of PBC in second generation patients was much younger (33.4+/-10.8 years) compared to median disease onset in general patients with PBC in Hiroshima (55.6+/-12 years). In fact, it was striking that the onset of disease in family members often occurred within a few years of each other. We also noted that sera of affected members had similar AMA reactive profiles against recombinant PDC-E2, BCKD-E2 and OGDC-E2; the major autoantigens of PBC. Similar HLA types were found within affected members of a pedigree but the data is limited because of absence of similar typing of unaffected members. The increased family history of PBC, and the earlier onset of disease in second generation members, suggests that environmental agents are an important risk factor for the development of disease. We suggest that genomic analysis in familial PBC will be important to identify the mechanisms of genetic susceptibility.     

Immunohistochemical analysis of biliary tract lesions.

The distinction among inflammatory, benign, and malignant lesions of the biliary tract can at times be difficult. Several methods have been used, including immunohistochemistry (IHC), with variable success. We evaluated a panel of IHC stains to determine their utility in discriminating between bile duct lesions. Formalin-fixed, paraffin-embedded 4-microm sections from 12 inflammatory lesions, 10 bile duct adenomas, and 13 bile duct carcinomas were immunostained using a modified avidin-biotin-complex technique after epitope enhancement using antibodies for p53, Ki-67, and bcl-2. For p53 and bcl-2, greater than 1% of cells staining positive was interpreted as positive. The proliferation index was calculated by determining the number of Ki-67-positive cells in a 1000 cell count. In the inflammatory group, 0 of 12 reacted with anti-p53, 2 of 12 were positive with anti-bcl-2, and the proliferation index with was 22.9% +/- 3.9%. Two of 10 bile duct adenomas showed reactivity with anti-bcl-2, and none were decorated with anti-p53 or Ki-67. In the carcinoma group, 6 of 13 were positive with anti-p53, 9 of 12 were positive with anti-bcl-2, and the proliferation index was 35.3% +/- 5.5%. The proliferation rates differed significantly between groups (P < 0.05). The presence of bcl-2 and p53 immunoreactivity coupled with a high proliferative rate in a biliary tract lesion suggests a malignant process. A panel using these antibodies may be useful in difficult cases.     

Oncocytic differentiation in intrahepatic biliary cystadenocarcinoma.

An intrahepatic biliary cystadenocarcinoma in a 56-yr-old white man was characterized by pronounced oncocytic differentiation. Grossly the tumor was a well-demarcated cyst filled with numerous branching papillary fronds. Most tumor cells had abundant granular, intensely eosinophilic cytoplasm on light microscopic examination and large numbers of densely packed mitochondria by electron microscopy. Mucin-secreting cells were also present. The patient returned 20 mo after resection of the primary tumor with recurrent tumor in the liver and widely disseminated disease throughout the abdominal cavity, and he died 5 mo later. Although less differentiated, the recurrent tumor again contained greatly increased numbers of mitochondria. The partial loss of oncocytic differentiation in the evolution of the present case and the benign nature of purely oncocytic tumors suggest that in the presence of mixed histologic features the potential for tumor progression is primarily determined by the lesser differentiated or nononcocytic component. To the best of our knowledge, oncocytic differentiation has not been previously described in biliary neoplasia.     

Circadian rhythm of biliary excretion and its control mechanisms in rats with chronic biliary drainage.

Rats with chronic biliary drainage under a rigid lighting schedule (light on at 6 A.M. and off at 6 P.M.) exhibited a remarkable circadian rhythm of bile flow, biliary concentrations and excretory rates of bile salts, cholesterol, and phospholipid. The peak was attained at midnight and nadir at noon except for the peak concentrations of cholesterol and phospholipid occurring at 8 P.M. Cholesterol feeding abolished the circadian rhythm of biliary cholesterol and phospholipid concentrations but not their excretory rates because the daily fluctuation of the bile flow remained unchanged. Bilateral vagotomy enhanced the bile flow rate and shifted the peak of circadian rhythm of all parameters except bile salt 4 h earlier. Bilateral adrenalectomy abolished the circadian variation of the concentration of cholesterol and phospholipid and minimized that of bile salt, but the daily fluctuation of their excretory rates persisted in a lower amplitude. The studies suggested that such circadian rhythm might be controlled simultaneously by multiple factors and could not be entirely abolished by any single special treatment.     

Accuracy of staging in primary biliary cirrhosis.

AIMS: To evaluate sampling variability of liver biopsy in patients with primary biliary cirrhosis (PBC). METHODS: Sections from 50 PBC liver specimens obtained at transplantation were examined. The degree of fibrosis was assessed on a scale of 0-4 using two methods: (1) simulated needle biopsy in fields approximately the size of conventional needle biopsy; and (2) whole section scanning in areas with little and extensive fibrosis. RESULTS: Considerable variation in the range of stages of fibrosis was found when the whole section scanning method was used. Only 10 (20%) samples had a consistent degree of fibrosis in all sections scanned. By contrast, the same fibrosis stage was assigned in 30 (60%) specimens examined using the simulated needle biopsy method. When the results obtained by the two methods were compared, there was a discrepancy of one or two stages in 32 samples. This discrepancy was the result of discovering areas with a lesser degree of fibrosis in whole sections compared with the simulated needle biopsy specimens. CONCLUSION: There is considerable variation in the degree of fibrosis in the livers of patients with PBC, even when end stage specimens obtained at transplantation are examined. Consistent results were obtained when simulated needle biopsy specimens were examined. This, however, may be a reflection of the procedure applied when staging liver needle biopsy specimens, where the greatest degree of abnormality is used in determining the stage. The practice of staging of PBC in small needle biopsy specimens is valuable as long as the appearances are interpreted with caution, bearing in mind that there is considerable variability in the degree of fibrosis.     

Endoscopic biliary drainage for severe acute cholangitis.

BACKGROUND. Emergency surgery for patients with severe acute cholangitis due to choledocholithiasis is associated with substantial morbidity and mortality. Because recent results suggested that emergency endoscopic drainage could improve the outcome of such patients, we undertook a prospective study to determine the role of this procedure as initial treatment. METHODS. During a 43-month period, 82 patients with severe acute cholangitis due to choledocholithiasis were randomly assigned to undergo surgical decompression of the biliary tract (41 patients) or endoscopic biliary drainage (41 patients), followed by definitive treatment. Hospital mortality was analyzed with respect to the use of endoscopic biliary drainage and other clinical and laboratory findings. Prognostic determinants were studied by linear discriminant analysis. RESULTS. Complications related to biliary tract decompression and subsequent definitive treatment developed in 14 patients treated with endoscopic biliary drainage and 27 treated with surgery (34 vs. 66 percent, P greater than 0.05). The time required for normalization of temperature and stabilization of blood pressure was similar in the two groups, but more patients in the surgery group required ventilatory support. The hospital mortality rate was significantly lower for the patients who underwent endoscopy (4 deaths) than for those treated surgically (13 deaths) (10 vs. 32 percent, P less than 0.03). The presence of concomitant medical problems, a low platelet count, a high serum urea nitrogen concentration, and a low serum albumin concentration before biliary decompression were the other independent determinants of mortality in both groups. CONCLUSIONS. Endoscopic biliary drainage is a safe and effective measure for the initial control of severe acute cholangitis due to choledocholithiasis and to reduce the mortality associated with the condition.     

Experimental bacterial infection of the biliary tract.

The bacterial species commonly found in the human obstructed biliary tract were studied in an animal model of acute hepato-cholangitis. A rank order of their virulence and persistence in the bile and liver was shown which corresponded well to the clinical effects in the animals and also to the prevalence of bile bacteria in the benign bile duct stricture of man. Anaerobic organisms were found to be of low pathogenicity.     

Serum gamma-glutamyltransferase isoenzymes in extrahepatic biliary obstruction.

The gamma-glutamyltransferase isoenzymes in the sera of patients with extrahepatic biliary obstruction have been studied, using electrophoretic, gel filtration, and ultracentrifugation techniques, and compared with those present in normal sera. Five isoenzymes were shown to exist in patients' sera, three of which were not demonstrated in normal sera. The observations are discussed in relation to the influence of biliary regurgitation and the possible solubilisation of membrane-bound enzymes. The results are compared with those of previous studies on alkaline phosphatase.     

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.