Felzen, Antonia

Cholangiocytes are specialized epithelial cells that line the intrahepatic and extrahepatic biliary tree and play a critical role in bile modification, liver homeostasis, and response to injury. Cholangiocytes exhibit notable heterogeneity and plasticity, and their dysfunction is central to a spectrum of diseases targeting the bile ducts, collectively called cholangiopathies. These disorders include genetic, infectious, immune-mediated, and malignant diseases, with primary sclerosing cholangitis (PSC) representing one of the most complex and enigmatic of these disorders. PSC is a progressive, fibro-inflammatory disease of the bile ducts that is closely linked to inflammatory bowel disease, carries a heightened risk of cancer, and lacks any approved therapies. This review explores the biology of cholangiocytes, including their development, functional plasticity, and roles in secretion, absorption, and cellular signaling. We provide a detailed examination of cholangiopathies, particularly PSC, a complex cholangiopathy characterized by a paradoxical state of cholangiocyte senescence and hyperproliferation. We describe how immune cell dysfunction, the gut microbiome, genetic predispositions, and environmental factors converge to mediate PSC pathogenesis. We revisit the foundational technologies that empowered early discoveries and shaped the field as we know it today. We also explore how newer techniques such as organoid cultures, single-cell transcriptomics, epigenomics, and spatialomics have transformed our modern understanding of biliary pathophysiology. Finally, we provide an overview of existing rodent models of cholangiopathies and discuss their relevance to human disease. PSC remains therapeutically unaddressed, and thus ongoing multidisciplinary efforts are essential to developing targeted interventions. This review serves as a comprehensive resource for researchers and clinicians navigating the rapidly evolving landscape of cholangiocyte-centered liver disease research.

Background: The sural nerve is widely used as a nerve graft for various types of peripheral nerve repair due to its ease of harvest and acceptable donor-site morbidity. Nevertheless, certain clinical scenarios, such as cable grafting or multiple cross-face nerve grafts, require grafts longer than the typical 35 cm. This study aims to investigate the anatomic feasibility and clinical safety of an extended sural nerve harvest above the popliteal crease by interfascicular dissection. Methods: An anatomic study using 5 fresh-frozen cadaver legs was conducted, focusing on identifying the anatomic relationship of the sural nerve above the popliteal crease to its surrounding structures and nerve histopathology. A retrospective review was performed of all patients who underwent an extended sural nerve harvest, and patient outcomes, including nerve graft length and postoperative complications, were reviewed to evaluate the clinical feasibility of the extended harvest technique. Results: Anatomic dissection revealed that interfascicular dissection allowed for an additional 14.3 ± 6 cm of nerve length, achieving a total graft length of 49.1 ± 5 cm. Histologic analysis showed no significant differences in fascicle number or axon count along the nerve. A retrospective review, which included 7 adults and 2 pediatric patients, demonstrated that an extended sural nerve harvest was feasible and safe. The maximum graft length was 55 cm, and no intraoperative complications or functional deficits were reported. Conclusion: The extended sural nerve harvest above the popliteal crease with a step-incision approach was both anatomically feasible and clinically safe, providing additional graft length without increasing donor-site morbidity.