Peribiliary Glands Research Articles

Perihilar Cholangiocarcinoma Originating in Peribiliary Glands: Insights from a Case without Precancerous Lesions

Perihilar Cholangiocarcinoma Originating in Peribiliary Glands: Insights from a Case without Precancerous Lesions

Impact of aging on peribiliary glands in ischemia-reperfusion injury.

The detailed mechanisms underlying the development of ischemia-type biliary lesions (ITBLs) in aged donor grafts remain unclear. In the present study we aimed to investigate the impact of aging on the response of the peribiliary gland (PBG) to ischemia-reperfusion injury (IRI) and its temporal changes. Experiments were performed using a 90-min partial warm liver ischemia model in male Wistar rats of two age groups: young (7-8 weeks old) and old (52-60 weeks old). Liver tissues were obtained 24, 72, and 168 h after IRI. Histopathological and immunohistochemical assessments of the perihilar bile duct (PHBD), including the PBG, distal to the clip-clamped site were performed. Young rats showed little change in the bile duct tissues after IRI. However, old rats showed an increased PBG volume in the PHBD and marked PBG cell proliferation 24 h after IRI. Bile duct wall thickening with narrowing of the lumen peaked 72 h after IRI. Mucus production and oxidative stress in the PBG were significantly higher in old than in young rats after IRI. These findings showed a trend toward improvement 168 h after IRI. Age-dependent differences in the response of the PBG to IRI may be related to differences in ITBL frequency.

Peribiliary cysts: uncommon mimickers of hepatic and biliary cystic lesions.

Peribiliary cysts (PC) are dilatations of the extramural peribiliary glands, with a very characteristic imaging pattern in the contexts of hepatobiliary diseases, idiopathic portal hypertension, adult-type polycystic disease of the liver and kidneys, solitary nonparasitic cysts, and systemic infections. The clinical relevance of PC is related to the fact that their presence may indicate underlying pathologies (such as those mentioned above) and may be considered as a potential marker of liver disease progression. Although imaging findings are quite characteristic, recognizing their main differential diagnoses, including malignancies, can be challenging but are essential to avoiding diagnostic errors.

PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice

The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease. The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the effectiveness of an Aurka inhibitor. We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as 1 month after birth. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated disease progression, potentially by downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expression of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression. Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum that was dependent on Aurka. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA. The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition, cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted disease progression. This model will be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.

Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.

Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a primary liver tumor that accounts for 2% of all cancer-related deaths worldwide yearly. It can arise from cholangiocytes of biliary tracts, peribiliary glands, and possibly from progenitor cells or even hepatocytes. CCA is characterized by high chemoresistance, aggressiveness, and poor prognosis. Potentially curative surgical therapy is restricted to a small number of patients with early-stage disease (up to 35%). Accumulating evidence indicates that CCA is an oxidative stress-driven carcinoma resulting from chronic inflammation. Oxidative stress, due to enhanced reactive oxygen species (ROS) production and/or decreased antioxidants, has been recently suggested as a key factor in cholangiocyte oncogenesis through gene expression alterations and molecular damage. However, due to different experimental models and conditions, contradictory results regarding oxidative stress in cholangiocarcinoma have been reported. The role of ROS and antioxidants in cancer is controversial due to their context-dependent ability to stimulate tumorigenesis and support cancer cell proliferation or promote cell death. On these bases, the present narrative review is focused on illustrating the role of oxidative stress in cholangiocarcinoma and the main ROS-driven intracellular pathways. Heterogeneous data about antioxidant effects on cancer development are also discussed.

Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal

The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized. Pit cholangiocytes of extramural glands renewed the surface epithelium, whereas basally oriented cholangiocytes maintained the gland itself. In contrast, basally positioned cholangiocytes replenished the surface epithelium in mural glands. Single-cell sequencing identified genes enriched in the base and surface epithelial populations, with trajectory analysis showing graded gene expression between these compartments. Epithelia were plastic, changing cellular identity upon fasting and refeeding. Gain of canonical Wnt signaling caused basal cell expansion, gastric chief cell marker expression, and a decrease in surface epithelial markers. Our results identify the cellular hierarchy governing extrahepatic biliary epithelial renewal.

Histological Assessment of the Bile Duct before Liver Transplantation: Does the Bile Duct Injury Score Predict Biliary Strictures?

Histological injury to the biliary tree during organ preservation leads to biliary strictures after liver transplantation. The Bile Duct Injury (BDI) score was developed to assess histological injury and identify the grafts most likely to develop biliary strictures. The BDI score evaluates the bile duct mural stroma, peribiliary vascular plexus (PVP) and deep peribiliary glands (DPGs), which were correlated with post-transplant biliary strictures. However, the BDI score has not been externally validated. The aim of this study was to verify whether the BDI score could predict biliary strictures at our transplant centre. Brain-dead donor liver grafts transplanted at a single institution from March 2015 to June 2016 were included in this analysis. Bile duct biopsies were collected immediately before transplantation and assessed for bile duct injury by two blinded pathologists. The primary outcome was the development of clinically significant biliary strictures within 24 months post-transplant. Fifty-seven grafts were included in the study which included 16 biliary strictures (28%). Using the BDI score, mural stromal, PVP and DPG injury did not correlate with biliary strictures including Non-Anastomotic Strictures. Severe inflammation (>50 leucocytes per HPF) was the only histological feature inversely correlated with the primary outcome (absent in the biliary stricture group vs. 41% in the no-stricture group, p = 0.001). The current study highlights limitations of the histological assessment of bile duct injury. Although all grafts had bile duct injury, only inflammation was associated with biliary strictures. The BDI score was unable to predict post-transplant biliary strictures in our patient population.

The Effect of Continuous Liver Normothermic Machine Perfusion on the Severity of Histological Bile Duct Injury.

Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, and thrombosis. A bivariate linear model compared BDIS (estimate, CI) between groups. Sixty-five transplants and 85 biopsies were analysed. Twenty-three grafts were preserved with SCS and 42 with NMP, with comparable baseline characteristics except for a shorter cold ischemic time in NMP. The BDIS increased over time regardless of preservation type (p = 0.04). The BDIS estimate was higher in NMP [8.02 (7.40-8.65)] than in SCS [5.39 (4.52-6.26), p < 0.0001] regardless of time. One patient in each group developed ischemic cholangiopathy, with a BDIS of 6 for the NMP-preserved liver. In six other NMP grafts, BDIS ranged 7-12 without development of ischemic cholangiopathy. In conclusion, BDIS increases over time, and the higher BDIS in NMP did not increase ischemic cholangiopathy. Thus, BDIS may overestimate this risk after liver NMP.

Development of pancreatic islet cells in the extrahepatic bile ducts of rats with experimentally-induced metabolic syndrome

Context There is data about the existence of some endocrine cells in the epithelial layer of the bile duct in humans and rats. Objective We evaluated Ghrelin-, Insulin-, Glucagon- and Somatostatin-positive cells in peribiliary glands, mast cells, and nerve fibres. Materials and methods Wistar rats were used for dietary manipulation with a 15% fructose solution for 12 weeks. Tissue samples were elaborated with immunohistochemistry for Insulin, Glucagon, Ghrelin, and Somatostatin. Glucose and lipid parameters were studied. Results In treated animals, Ghrelin+ and Insulin+ cells in perybiliary glands (PBGs) were significantly increased. In the male fructose group there was a significant increase of the homeostasis model assessment insulin resistance (HOMA-IR). Conclusions Stem/progenitor cells in extrahepatic bile tree (EHBT) could be a source of Insulin-producing cells in metabolic syndrome. Fructose treatment induces the increase of Ghrelin+ and Insulin+ cells in PBGs and the elevation of Insulin and Ghrelin plasma concentration.

A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia

Biliary atresia (BA) is an obstructive cholangiopathy that initially affects the extrahepatic bile ducts (EHBDs) of neonates. The etiology is uncertain, but evidence points to a prenatal cause. Fetal tissues have increased levels of hyaluronic acid (HA), which plays an integral role in fetal wound healing. The objective of this study was to determine whether a program of fetal wound healing is part of the response to fetal EHBD injury. Mouse, rat, sheep, and human EHBD samples were studied at different developmental time points. Models included a fetal sheep model of prenatal hypoxia, human BA EHBD remnants and liver samples taken at the time of the Kasai procedure, EHBDs isolated from neonatal rats and mice, and spheroids and other models generated from primary neonatal mouse cholangiocytes. A wide layer of high molecular weight HA encircling the lumen was characteristic of the normal perinatal but not adult EHBD. This layer, which was surrounded by collagen, expanded in injured ducts in parallel with extensive peribiliary gland hyperplasia, increased mucus production and elevated serum bilirubin levels. BA EHBD remnants similarly showed increased HA centered around ductular structures compared with age-appropriate controls. High molecular weight HA typical of the fetal/neonatal ducts caused increased cholangiocyte spheroid growth, whereas low molecular weight HA induced abnormal epithelial morphology; low molecular weight HA caused matrix swelling in a bile duct-on-a-chip device. The fetal/neonatal EHBD, including in human EHBD remnants from Kasai surgeries, demonstrated an injury response with prolonged high levels of HA typical of fetal wound healing. The expanded peri-luminal HA layer may swell and lead to elevated bilirubin levels and obstruction of the EHBD. Biliary atresia is a pediatric cholangiopathy associated with high morbidity and mortality rates; although multiple etiologies have been proposed, the fetal response to bile duct damage is largely unknown. This study explores the fetal pathogenesis after extrahepatic bile duct damage, thereby opening a completely new avenue to study therapeutic targets in the context of biliary atresia.

Clinical, histopathological, and immunohistochemical spectrum of hepatolithiasis: a tertiary care center-based study from north India.

Hepatolithiasis (HL), an uncommon disease among Indians, occurs due to a complex interplay of various structural and functional factors. We retrospectively evaluated the clinical and histopathological spectrum of HL (N = 19) with immunohistochemical evaluation for biliary apomucins and canalicular transporter proteins, both crucial for lithogenesis. Nineteen surgically resected cases were included. Histopathology was systematically evaluated. Immunohistochemistry for apomucins (MUC1, MUC2, MUC4, MUC5AC, and MUC6) and canalicular transporter proteins (BSEP and MDR3) was applied to all cases. The median age was 51years with female preponderance (F:M = 1.4:1). The stone was cholesterol-rich in 71.4% and pigmented in 28.6% (n = 14). Histopathology showed variable large bile-duct thickening due to fibrosis and inflammation with peribiliary gland hyperplasia. Structural causes (Caroli disease, choledochal cyst, and post-surgical complication) were noted in 15.8% of cases (secondary HL). Expression of gel-forming apomucin MUC1, MUC2, and MUC5AC was seen in either bile duct epithelia or peribiliary glands in 84.2%, 10.5%, and 84.2% cases respectively. Loss of canalicular expression of MDR3 was noted in 42.1% of cases while BSEP was retained in all. Primary HL in the north Indian population can be associated with the loss of MDR3 expression (with retained BSEP) and/ or a shift in the phenotype of biliary apomucins to gel-forming apomucins. The former factor alters the bile acid/ phospholipid ratio while the latter parameter promulgates crystallization. In conjunction, these factors are responsible for the dominantly cholesterol-rich stones in the index population.

A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs and humans

A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner’s Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of intrahepatic and extrahepatic biliary trees, and in pancreatic duct glands (PDGs) of intrapancreatic biliary trees, collectively supporting hepatic and pancreatic regeneration postnatally. The network is found in humans postnatally throughout life and, so far, has been demonstrated in pigs postnatally at least through to young adulthood. These stem/progenitors in vivo in pigs are in highest numbers in Brunner’s Glands and in PDGs nearest the duodenum, and in humans are in Brunner’s Glands and in PBGs in the hepato/pancreatic common duct, a duct missing postnatally in pigs. Elsewhere in PDGs in pigs and in all PDGs in humans are only committed unipotent or bipotent progenitors. Stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on correlation, hierarchical clustering, differential gene expression and principal component analyses (PCA). Gene expression includes representative traits of pluripotency genes (SOX2, OCT4), endodermal transcription factors (e.g. SOX9, SOX17, PDX1), other stem cell traits (e.g. NCAM, CD44, sodium iodide symporter or NIS), and proliferation biomarkers (Ki67). Hepato/pancreatic multipotentiality was demonstrated by the stem/progenitors’ responses under distinct ex vivo conditions or in vivo when patch grafted as organoids onto the liver versus the pancreas. Therefore, pigs are logical hosts for translational/preclinical studies for cell therapies with these stem/progenitors for hepatic and pancreatic dysfunctions.

Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion.

End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP. Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial. After NMP, livers were either secondary declined (n = 17) or accepted for transplantation (n = 25) based on the chemical composition of bile and perfusate samples. Bile duct biopsies were taken before and after NMP and assessed using an established histological injury severity scoring system and a comprehensive immunohistochemical assessment focusing on peribiliary glands (PBGs), vascular damage, and regeneration. Bile ducts of livers that were transplanted after viability testing during NMP showed better preservation of PBGs, (micro)vasculature, and increased cholangiocyte proliferation, compared with declined livers. Biliary bicarbonate, glucose, and pH were confirmed as accurate biomarkers of bile duct vitality. In addition, we found evidence of PBG-based progenitor cell differentiation toward mature cholangiocytes during NMP. Favorable bile chemistry during NMP correlates well with better-preserved biliary microvasculature and PBGs, with a preserved capacity for biliary regeneration. During NMP, biliary tree progenitor cells start to differentiate toward mature cholangiocytes, facilitating restoration of the ischemically damaged surface epithelium.

Features of the Peribiliary Glands of the Extrahepatic Biliary Tract in the Elderly and Long-Living Individuals

The aim of the study was to analyse histologically and morphometrically the peribiliary glands of the extrahepatic biliary tract in the elderly and long-living people.Material and methods. The study included wholemounts of the gallbladder, the cystic, hepatic and common bile ducts obtained from the corpses of both sexes aged 22 to 35 years (n=16) and older than 76 years (n=39). Macro-microscopy was used to evaluate the number, localization, sizes and shape of the glands, the area of the lumen of the excretory duct orifices, the area of the initial section of the glands, the number of initial (terminal) parts and the proportion of epithelial parenchyma in their composition.Results. With age, there is a decreased proportion of "complexly branched" glands with a significant number of initial sections and excretory ducts of the 1st order. The proportion of "simple" glands, with one initial section increases to 70.2–78.3% in the senile age, while it is 41.0–52.1% in people of mature age. In long-living people, there is an increased number (up to 70–85%) of glands with ampullar extensions of the common excretory duct. The total number, density of gland localization, the length and width of the initial section of the peribiliary glands tend to decrease from the period of mature age to longevity. In senile age, the size and quantitative parameters of the glands stabilize, and do not modify in long-living people.Conclusion. The results of the morphological analysis demonstrate that there is no progression of involutive changes in the peribiliary glands of the extrahepatic biliary tract from senile age to the period of longevity. In some cases, long-living individuals manifest compensatory-adaptive reactions, such as an increased severity of the epithelial parenchymal component in the composition of the glands and an increased proportion of glands with an ampullar expansion of the common excretory duct.

Biliary Atresia Remnants Revisited: Myogenesis, Hepatic Duct-Like Structures, and Fate of Peribiliary Glands.

Proximal levels of excised remnants from youngest infants may reveal early features of biliary atresia (BA). A targeted IHC survey was applied to 34 most proximal 2 levels in 17 BA remnants excised at age 10-74 days including 7 = <30 days old and 6 control hepatic ducts (HD). Severity of inflammation and extent of active fibroplasia do not distinguish proximal remnants in younger (n = 7) and older (n = 10) infants. In 27/34 levels of 14/17 remnants, reactive stroma is focally SM-MHC-2 (+), marking smooth muscle myosin, termed reactive myogenesis (RM), that is absent in controls. RM facilitates identification of 3 novel hepatic duct remnants (HDR): an HD-like collagen collar lined by degenerating cholangiocytes (n = 5); erosion defects in loose reactive stroma (n = 14); solitary foci of hyperplastic squamoid epithelium (n = 4). Peribiliary glands are either hyperplastic or atretic and typically lack RM. Minimally inflammed end-stage lesions in BA remnants occur at youngest ages favoring prenatal onset. Three novel HDR are defined. RM, a useful surrogate for HDR, is a prevalent inappropriate stromal reaction in proximal remnants of uncertain biological significance. RM is the source of mature smooth muscle in BA remnants.

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury.

Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

Peribiliary gland injury by floxuridine may be an early mechanistic insult en route to sclerosis

Background: Hepatic artery infusion pumps (HAIP) are being increasingly employed in the management of metastatic colorectal cancer and cholangiocarcinoma secondary to encouraging response rates in most patients. However, efficacy is limited in many patients by biliary toxicity, which requires vigilant monitoring of hepatic biochemistry and frequent dose reductions to avoid secondary sclerosing cholangitis. Although dexamethasone is employed to limit this drug-induced adverse event, little is known about the early (and possibly intervenable) mechanism(s) of toxicity. We hypothesize that mitigation of biliary sensitivity to floxuridine (FUDR) will allow patients to receive more FUDR, increasing the oncologic efficacy of therapy while simultaneously minimizing morbidity.

Isolated Hepatic Polykystosis: About a Case in the Hépato-Gastroenterology Department of the National Hospital of Niamey

Polycystic liver disease is an autosomal dominant disorder, rare and benign in the majority of cases [1]. It is frequently associated with polycystic kidney disease, but can also be isolated in rare cases. Liver cysts result from abnormal growth of the biliary epithelium (cholangiocytes) or dilation of the peribiliary glands, due to the persistence of embryonic biliary structures. Isolated polycystic liver disease is generally asymptomatic, women are more affected than men and also have a greater number of cysts [2]. We report the case of a 40-year-old asymptomatic man with isolated polycystic liver disease Gigot III discovered during a health check-up. The clinical examination showed hepatomegaly without pain, of firm consistency, smooth surface, sharp lower edge with a hepatic arrow at 17cm. The kidneys are devoid of cysts, the liver function as well as the renal function are normal.

Cholangiocarcinoma of the Common Bile Duct and Hepatic Hilum (Bismuth II) Complicated by Covid-19 – Case Report

Background Cholangiocarcinoma is a rare tumour that originates from the epithelial lining and the peribiliary glands of the bile ducts. Our report’s scope pertains to the diagnosis of perihilar cholangiocarcinoma, which was first described by Klatskin. Unfortunately, patients ask for medical assistance only after the development of jaundice due to biliary obstruction. Achieving the best standard of care requires meticulous workup and evaluation through a multidisciplinary team to correctly determine the eligibility of a patient for resection surgery. Case presentation A 78 years old male patient presents with jaundice and pruritus. Total bilirubin level is 24 mg/dl and imaging studies show a 2×2.5 cm tumour of the hepatic hilum. After the necessary preoperative consults, the patient underwent a surgical procedure, consisting of hepatic hilum resection, separate left and right hepatico-jejunal anastomoses en-Roux. Anastomoses are protected by 2 Kehr drains on the ducts. The first six postoperative days were uneventful, but on the 7 th day the patient develops notable abdominal meteorism and diarrhoea of mostly biliary content for the following 3 days. The case is complicated by episodes of excessive haematochezia. Fibroscopy shows no active haemorrhaging site, but CT scan notes small bowel microinfarctions thus explaining haematochezia. It also confirms COVID-19 with a bilateral interstitial pneumonia and a microthrombus on the right peripheral lung segments. Following a careful treatment regimen, the patient was discharged in good health from the hospital. Discussion Studies show that COVID-19 gastro-intestinal symptoms were anorexia, diarrhoea, nausea, vomiting or diffuse abdominal pain. Haematochezia has been unusual. Hospitalized patients, on a bed-rest regimen with comorbidities had a tendency for small bowel microinfarctions. It is widely thought that ischaemia and bowel hypoperfusion is related to the cytokine storm, not a direct effect of the virus. A cytokine storm may be followed by an abnormal coagulation function, as in our patient. Conclusion Prior to major surgeries, especially in the hepato-biliary apparatus there is a mandatory evaluation to determine the operability of a patient. Not only the extent of the primary tumour, but also the comorbidities need to be taken into account. Following a rigorous surgical technique, a close monitoring of the patient and involving a multidisciplinary team of radiology, infectious disease, gastro-hepatology, oncology and intensive care doctors in the treatment plan has successfully treated such a rare and complex case. Keywords: General Surgery, Bile Duct Tumor, Cholangiocarcinoma, Bismuth-Corlette, COVID-19. DOI: 10.7176/ALST/96-03 Publication date: December 31 st 2022