The development of the intrahepatic bile ducts in man was studied using an immunohistochemical technique on 56 liver specimens ranging in age from 6 weeks of gestation to 8 months after birth. On paraffin sections, two monoclonal anticytokeratin antibodies (CAM 5.2 and KL-1) that normally stain both hepatocytes and bile duct cells and two polyclonal anticytokeratin antisera that in normal adult liver stain bile ducts only were applied. For immunohistochemical staining of cryostat sections (only available from 14 weeks of gestation on), four monoclonal antibodies specifically directed against individual cytokeratin polypeptides 7,8, 18 and 19 were used. Adult human hepatocytes contain cytokeratin 8 and 18 whereas bile duct cells also express cytokeratin 7 and 19 in addition to cytokeratin 8 and 18. On paraffin sections, primitive hepatocytes were stained with monoclonal antibodies CAM 5.2 and KL-1 from 6 weeks of gestation on. On cryostat sections, they were positive with monoclonal antibodies anticytokeratin 8 and 18 from the earliest time point examined (14 weeks). From 9 weeks of gestation on, portal vein branches were surrounded by a layer of cells showing a stronger positive reaction with monoclonal antibodies CAM 5.2 and KL-1 on paraffin sections and with monoclonal antibodies anti-cytokeratin 8 and 18 on cryostat sections (only available from 14 weeks on). This layer, referred to as the ductal plate, first appeared around large portal vein branches close to the hilum and subsequently around more peripheral branches. The duct plates became duplicated over variably long segments of their perimeter, lumina appeared and tubular structures were formed. The latter gradually became incorporated in the connective tissue surrounding the portal vein, resulting in the appearance of individualized bile ducts. Ductal plate cells were stained by both polyclonal anticytokeratin antisera on paraffin sections. On cryostat sections (available from 14 weeks of gestation on), they were immunoreactive for cytokeratin 19 but negative with the monoclonal antibody directed against cytokeratin 7 until 20 weeks of gestation. From then on, weakly positive staining for cytokeratin 7 was detected, but staining intensity subsequently increased and reached the level observed in adult liver at 1 month after birth. At birth, the smallest branches of the portal vein were still surrounded by a discontinuous ductal plate. We conclude that intrahepatic bile duct cells develop from hepatocytes around branches of the portal vein.(ABSTRACT TRUNCATED AT 400 WORDS)
Anatomical and histopathological findings in 12 cases of trisomy 13 syndrome (nine with classic full trisomy and three with trisomy 13 and an unbalanced Robertsonian 13/13 translocation) are reported. Emphasis is on the brain defects, cardiovascular anomalies, and histological organ dysplasia. Eight patients showed abnormal development of the forebrain and midline facial structures (holoprosencephaly). Cardiovascular malformations were invariably present, the leading malformation being an infundibular ventricular septal defect often in combination with dextroposition of the aorta and abnormalities of the semilunar valves. Histological abnormalities giving evidence of organ dysplasia were observed in the central nervous system, eyes, pancreas, kidneys, and ovaries. Mild cystic renal dysplasia was a constant feature. Foci of persistent nodular renal blastema were found in six cases. The pancreatic dysplasia appears to be pathognomonic for trisomy 13. These observations illustrate the importance of pathological studies in the recognition of chromosome abnormalities and, more specifically, of trisomy 13 syndrome. Based on autopsy data, trisomy 13 can be diagnosed - or ruled out - with certainty, even in the absence of karyotyping.
Introduction: The Standardized Uptake Value (SUV) in single lesions on 18 F-FDG PET/CT scans and serum S-100B concentrations are inversely associated with disease-free survival in stage IV melanoma. The aim of this study was to assess the association between biomarkers (S-100B, LDH) and the PET-derived metrics SUV mean/max , metabolic active tumor volume (MATV), and total lesion glycolysis (TLG) in stage IV melanoma in order to understand what these biomarkers reflect and their possible utility for followup. Methods: In 52 stage IV patients the association between PET-derived metrics and the biomarkers S-100B and LDH was assessed and the impact on survival analyzed.Results: S-100B was elevated (>0.15 mg/l) in 37 patients (71%), LDH in 11 (21%). There was a correlation between S-100B and LDH (R 2 ¼ 0.19). S-100B was correlated to both MATV (R 2 ¼ 0.375) and TLG (R 2 ¼ 0.352), but LDH was not. Higher MATV and TLG levels were found in patients with elevated S-100B (p < 0.001) and also in patients with elevated LDH (>250 U/l) (p < 0.001). There was no association between the biomarkers and SUV mean/max . Survival analysis indicated that LDH was the only predictor of melanoma-specific survival. Conclusion:In newly diagnosed stage IV melanoma patients S-100B correlates with 18 F-FDG PET/CT derived MATV and TLG in contrast to LDH, is more often elevated than LDH (71% vs. 21%) and seems to be a better predictor of disease load and disease progression. However, elevated LDH is the only predictor for survival. The biomarkers, S-100B and LDH appear to describe different aspects of the extent of metastatic disease and of tumornecrosis.
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