Biliary atresia (BA), which is thought to result from progressive destruction of the bile ducts by a necroinflammatory process, is the most common cause of obstructive jaundice in infancy. Abnormalities in the cell turnover of remodelling ductal plates are considered one of the important aetiological factors in this disorder, but little work has been done on this topic. Programmed cell death or apoptosis was therefore examined by TdT‐mediated dUTP biotin nick end labelling (TUNEL) and cell proliferation by Ki67 immunostaining in 34 cases of BA. The results were compared with normal control liver (five cases) and congenital dilatation of the bile ducts (CDB, five cases) in order to study the cell turnover or tissue dynamics of BA. The TUNEL labelling index (LI) in bile ducts (48·9±13·2 per cent) was significantly higher than that of the control normal liver (3·6±2·8 per cent) and of CDB (2·5±5·1 per cent). The Ki67 LI in the bile ducts of BA (15·0±5·57 per cent) was also significantly higher than that of CDB (8·6±5·4 per cent). No significant differences of the TUNEL and Ki67 LIs in hepatocytes were, however, observed between BA, CDB, and normal liver. The TUNEL LI was significantly higher than the Ki67 LI in the bile ducts of BA. BA is therefore associated with increased and disorganized cell turnover of the bile ducts, which is related to malformation of the ductal plate or abnormal bile duct development. Copyright © 1998 John Wiley & Sons, Ltd.

Abstract.Among sex steroids, especially estrogen metabolism has been considered to play a role in the function and pathology of human veins. We investigated the expression and activity of the estrogen-producing enzyme aromatase and estrogen receptor (ER) in human vena cava to assess possible in situ biosynthesis of estrogens and their modes of action. We first examined aromatase expression by immunohistochemistry in human inferior vena cava obtained from 29 autopsy cases (11 males, 18 females, 63.6±3.0 years old). We then semiquantitated the level of aromatase mRNA by reverse transcriptase-polymerase chain reaction in 24 cases and aromatase activity by 3H-water assay in 15 cases to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon is of its gene and immunolocalization of 17,0-hydroxysteroid dehydrogenase type I (173-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen and ER. Aromatase and 17p-HSD I immunoreactivity were both detected in smooth muscle cells (SMC) of the media in all the cases and in endothelial cells (EC) in 20 and 22 cases, respectively. ER immunoreactivity was detected in SMC of vena cava in 21 cases. The amount of aromatase mRNA was significantly greater in the cases utilizing is (I.3) or id (P.11) of exon 1 (9 cases, 191.1 ±26.3 attomol/ng total RNA) than those utilizing l b (1.4) as the promoter (14 cases, 50.6± 13.0 attomol/ng total RNA) (p < 0.01). Significant correlation (p < 6.05) was observed between the amount of aromatase mRNA and aromatase activity in 15 cases examined. No significant correlation was detected between the amount of aromatase mRNA or aromatase labeling index and the ER status. These results suggest that estrone and estradiol are produced in the human vena cava and that their production is mediated by aromatase and 17,0-HSD I, respectively but not all of these locally synthesized estrogens may not work directly in situ. In postmenopausal women and men, estrogen biosynthesis is mainly peripheral, through conversion of androstenedione or C19 steroids from the adrenal cortex, ovary and/or testis [7]. This conversion is catalyzed by the enzyme complex cytochrome P450 aromatase.In humans, aromatase has been detected in numerous extragonadal tissues including adipocytes [8]

An unusual urachal lesion, which is a mucinous adenocarcinoma arising in a giant urachal cyst and is associated with pseudomyxoma peritonei and stromal osseous metaplasia of the cyst wall, was examined in a 45-year-old male. The cyst was encapsulated, measured 22 x 20 x 20 cm and weighed 3800 g. The unilocular cavity was filled with mucin. Most of the cystic cavity was lined with tall, simple or stratified columnar epithelium with a focus of papillary projection into the cavity. These findings suggest that this cystic lesion represents cystadenoma rather than a simple cyst. Foci of invasive moderately differentiated mucinous adenocarcinoma were detected in the area of macroscopic papillary fronds. Carcinoembryonic antigen and CA19-9 were immunohistochemically positive for tumor cells and their serum levels were also elevated. Stromal dystrophic calcification was extensively observed in the cyst wall with foci of osseous metaplasia. Mucinous implants, which histologically demonstrated adherent mucinous masses without epithelial components on the surface, were observed in the pelvic and abdominal cavity, indicating pseudomyxoma peritonei.