Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in C(max), and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in C(max) and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

A histopathological study of liver and biliary remnants in the long-term survivors (>10 years) of cases of biliary atresia.

Context: Biliary atresia (BA) is a destructive process affecting both extraand intra-hepatic bile ducts leading to fibrosis and obliteration of the biliary tree and cirrhosis usually within 2 years. Factors influencing the outcome of portoenterostomy (PE) have not been clearly defined. Aims: Our aim was to identify children with no evidence of liver disease 10 years or more after PE and to compare the pathology of liver and biliary remnants in this group with those associated with poor outcome. Settings and Design: Prospective observational study. Materials and Methods: Wedge biopsies of liver and portal remnants, taken at the time of PE, where available, were reviewed. The parameters studied were - presence of large bile ducts (>150 μ), degree of fibrosis and bile duct proliferation (BDP), presence of ductal plate malformation (DPM) and age at operation. Statistical Analysis Used: Fisher’s exact test with Freeman Halton extension for univariate analysis and Logistic regression analysis as multivariate analysis. Results: Of 68 cases operated between 1995 and 2001, 14 patients survived >10 years and 54 were associated with poor outcome. Large ducts were significantly more in survivors (70% vs. 26%, P = 0.02). DPM was not seen in any of the survivors and was present in 24% of poor outcome group. Fibrosis and BDP were also significantly less among the survivors (P < 0.001, P = 0.03, respectively). The mean ages at operation in the two groups were 66.8 and 89.6 days, respectively. Conclusion: From this study, we feel that lower degree of fibrosis and BDP, absence of DPM, presence of large ducts and younger age at operation were associated with better long-term outcome. Of these, degree of fibrosis was the most significant factor.

Meckel-Gruber Syndrome: An autopsy case report

Meckel-Gruber syndrome is a quite rare congenital disorder, characterized by posterior encepalocele, cleft palate and lip, polycystic kidneys, hepatic fibrosis with bile duct proliferation, and postaxial polydactyly and syndactyly. We experienced an autopsy case of M eckel-Gruber syndrome in a second baby of 28 year-old woman. At 26 weeks of gestation, congenital anomaly was detected on ultrasonographic examination and the pregnancy was terminated. Familial history was not noted.