Search

Reconstruction of extrahepatic bile ducts is a staple procedure of HPB surgery. The current standard for most cases is a nonanatomical bilioenteric reconstruction, a satisfactory option for the majority of patients. However, it cannot be used for a small number of selective cases (short bowel syndrome, severe abdominal adhesions), where an anatomical reconstruction with or without an interponate can be used. This review summarizes current knowledge about tissue and material usage for experimental and clinical anatomical bile duct reconstruction in the last 100 years. A Pubmed database was searched for published articles about anatomical extrahepatic bile duct reconstruction in experimental and clinical settings ranging from 1920 to 2022. To date, the truly optimal interponate material has not yet been found. However, evidence reveals important properties of such material, most importantly its biodegradability and neovascularization in the recipient's body. The role of internal bile duct stenting for anatomical reconstruction seems important for the outcome. Anatomical reconstruction of extrahepatic bile ducts is an uncommon but usable technique in unique cases when a nonanatomical reconstruction cannot be done. The optimal properties of interponate material for anatomical bile duct reconstruction have been more clarified, although further research is required., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Albadry, Küttner, Grzegorzewski, Dirsch, Kindler, Klopfleisch, Liska, Moulisova, Nickel, Palek, Rosendorf, Saalfeld, Settmacher, Tautenhahn, König and Dahmen.)

Background: ATP-binding cassette (ABC) transporters translocate various substances across cellular membranes. Their deregulation may cause cancer drug resistance or perturbations in the supply of building blocks for cancer cells and modify patients' prognosis. This study investigated protein expression and cellular localization of the previously suggested putative prognostic biomarkers - ABCB2/TAP1, ABCC7/CFTR, ABCC8/SUR1, and ABCD4 in patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: Protein expression and localization were assessed by immunohistochemistry in formalin-fixed paraffin-embedded primary tumor tissue blocks of 61 PDAC patients and associated with clinical data and the survival of patients., Results: No CFTR protein expression was observed in PDAC, while TAP1 and ABCC8 were expressed predominantly in the cytoplasm of tumor cells. Most samples (81 %) had detectable both membranous and cytoplasmic ABCD4 staining and 42 % had ABCD4 expressed in the apical orientation. Negative membranous ABCD4 staining was significantly more frequent in advanced stage III or IV tumors (p = 0.022). Small or medium counts of individual ABCC8-positive cells in the stroma surrounding tumor tubules were also more often found in stage III or IV (p = 0.044). Patients with moderate or strong ABCC8 cytoplasmic staining intensity in tumor cells had a 3.5-fold higher risk of disease progression than those with weak staining (p = 0.002)., Conclusions: The study shows for the first time that the cytoplasmic ABCC8 protein expression has prognostic value in PDAC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)