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Objectives: In patients with unresectable malignant hilar biliary obstruction (UMHBO), drainage of ≥ 50% liver volume correlates with better clinical outcomes. Accurately measuring the liver volume to be drained by biliary stents is required. We aimed to develop a novel method for calculating the drained liver volume (DLV) using a 3D volume analyzer (3D volumetry), and assess the usefulness for drainage in patients with UMHBO., Methods: Three-dimensional volumetry comprises the following steps: (1) manual tracing of bile duct using 3D imaging system; (2) 3D reconstruction of bile duct and liver parenchyma; and (3) calculating DLV according to the 3D distribution of bile ducts. Using 3D volumetry, we reviewed data of patients who underwent biliary drainage for UMHBO, calculated the DLV, and determined the association between DLV and biliary drainage outcome., Results: There were 104 eligible cases. The mean DLV was 708 ± 393 ml (53% ± 21%). and 65 patients (63%) underwent drainage of   ≥50% liver volume. The clinical success rate was significantly higher in patients with DLV ≥ 50% than in patients with DLV < 50% (89% vs. 28%, P < 0.001). The median time to recurrence of biliary obstruction (TRBO) and survival time were significantly longer in patients with DLV ≥ 50% than in patients with DLV < 50% (TRBO, 292 vs. 119 days, P = 0.03; survival, 285 vs. 65days, P = 0.004, log-rank test, respectively)., Conclusions: Three-dimensional volumetry, a novel method to calculate DLV accurately according to bile duct distribution was useful for drainage in UMHBO patients., (© 2024. The Author(s).)

Most precursor lesions and early cancerous changes in the gallbladder and bile ducts present as clinically/grossly inapparent lesions. Low-grade dysplasia is difficult to define and clinically inconsequential by itself; however, extra sampling is required to exclude accompanying significant lesions. For high-grade dysplasia ('carcinoma in situ'), a complete sampling is necessary to rule out invasion. Tumoral intramucosal neoplasms (ie, intracholecystic and intraductal neoplasia) form radiologically/grossly visible masses, and they account for (present in the background of) about 5% to 10% of invasive cancers of the region. These reveal a spectrum of papilla/tubule formation, cell lineages, and dysplastic transformation. Some subtypes such as intracholecystic tubular non-mucinous neoplasm of the gallbladder (almost never invasive) and intraductal oncocytic or intraductal tubulopapillary neoplasms of the bile ducts (may have a protracted clinical course even when invasive) are to be noted separately. Other types of intracholecystic/intraductal neoplasia have a high frequency of invasive carcinoma and progressive behavior, which often culminates in mortality., Competing Interests: Disclosure O Basturk has been supported in part by the Cancer Center Support Grant of the National Institutes of Health, United States/National Cancer Institute, United States under award number P30CA008748., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer., Case Presentation: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor., Conclusions: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca., (© 2024. The Author(s).)

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

We report a case of intraductal papillary neoplasms of the bile duct (IPNB) that metachronously developed twice in the downstream bile duct after radical resection. The first lesion was located in the left intrahepatic bile duct, the second lesion in the perihilar bile duct, and the third lesion in the distal bile duct. All lesions were IPNBs with associated invasive carcinoma (pancreatobiliary type). The depth of invasion was to the Glisson's capsule in the first lesion, to the subserosa in the second lesion, and to the fibromuscular layer in the third lesion, without lympho-vascular/perineural invasion and lymph-node metastasis. These were resected radically and had no biliary intraepithelial neoplasia and hyperplasia in the surrounding mucosa. In immunohistochemical examination, each lesion showed a different pattern. Although the downstream occurrence suggests intrabiliary dissemination, the mechanism of these metachronous developments may be multicentric. A literature review revealed that most metachronous cholangiocarcinomas have a grossly papillary appearance and tend to arise downstream. Our findings suggest that IPNB may develop metachronously in the residual bile duct after radical surgery, which may assist in early detection., (© 2023. Japanese Society of Gastroenterology.)

Background and Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood., Approach and Results: We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 ( Trem2 ) and osteopontin ( Spp1 ), markers assigned to hepatic bile duct-associated macrophages, and were enriched around the portal triad, which was confirmed in human PSC. Colitis induced monocyte/macrophage infiltration in the gut and liver, and enhanced cholestasis-induced MoMF- Trem2 and Spp1 upregulation, yet did not exacerbate liver fibrosis. Bone marrow chimeras showed that knockout of Spp1 in infiltrated MoMFs exacerbates inflammation in vivo and in vitro , while monoclonal antibody-mediated neutralization of SPP1 conferred protection in experimental PSC. In human PSC patients, serum osteopontin levels are elevated compared to control, and significantly increased in advanced stage PSC and might serve as a prognostic biomarker for liver transplant-free survival., Conclusions: Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Clonorchis sinensis is a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensis infection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown., Methods: Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples., Results: Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcus abundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensis may promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair., Conclusions: This study provides comprehensive insights into the pathological effects of C. sinensis infection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensis pathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions., (© F. Li et al., published by EDP Sciences, 2024.)

Objectives: The early life microbiome has been linked to inflammatory diseases in adulthood and a role for the microbiome in bile duct inflammation is supported by both human and murine studies. We utilized the NOD.c3c4 mouse model that develops a spontaneous immune-driven biliary disease with a known contribution of the microbiome to evaluate the temporal effects of the early life microbiome., Materials and Methods: Germ-free (GF) NOD.c3c4 mice were conventionalized into a specific pathogen free environment at birth (conventionally raised, CONV-R) or at weaning (germ-free raised, GF-R) and compared with age and gender-matched GF and conventional (CONV) NOD.c3c4 mice. At 9 weeks of age, liver pathology was assessed by conventional histology and flow cytometry immunophenotyping., Results: Neonatal exposure to microbes (CONV-R) increased biliary inflammation to similar levels as regular conventional NOD.c3c4 mice, while delayed exposure to microbes (GF-R) restrained the biliary inflammation. Neutrophil infiltration was increased in all conventionalized mice compared to GF. An immunophenotype in the liver similar to CONV was restored in both CONV-R and GF-R compared to GF mice displaying a proportional increase of B cells and reduction of T cells in the liver., Conclusions: Microbial exposure during early life has a temporal impact on biliary tract inflammation in the NOD.c3c4 mouse model suggesting that age-sensitive interaction with commensal microbes have long-lasting effects on biliary immunity that can be of importance for human cholangiopathies.

Introduction: The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree., Methods: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic. Histology was revised in all cases, and albumin ISH was automatically performed by the RNAscope®., Results: ISH was always negative in extrahepatic CCAs, only 1 perihilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p &lt; 0.001). Concerning CCA subtypes, mean cell positivity was 38.8 ± 29.8% in small-duct CCAs and 11.4 ± 21.9 in large-duct CCAs, respectively (p = 0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed &gt;5% positive cells (p = 0.002; odds ratio 14.7)., Conclusions: The introduction of more sensitive techniques changed the indications for ISH since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy.

A 58-year-old woman presented with a complaint of weight loss. Abdominal computed tomography showed dilatation of the biliary and pancreatic ducts and a mural nodule in the pancreatic duct. The diagnosis was intraductal papillary mucinous neoplasm(IPMN). Endoscopic retrograde cholangiopancreatography(ERCP)and cholangioscopy revealed a fistula between the common bile duct and the IPMN. A sudden increase in hepatobiliary enzymes was noted preoperatively. ERCP showed that the common bile duct was obstructed by mucus. A nasobiliary drainage tube was inserted into the bile duct endoscopically and kept open by daily tube washing, and the liver dysfunction improved. Total pancreatectomy, splenectomy, and regional lymph node dissection were performed. Histological examination confirmed that the primary tumor was mixed invasive intraductal papillary mucinous adenocarcinoma. The patient remains alive and well with no evidence of recurrence 18 months after resection.

Endoscopic biopsies from the ampulla of Vater are challenging due to specimen sampling limitation, small size, interventional artifacts, and the nature of local complex anatomy. We retrospectively reviewed 318 in-house ampulla of Vater biopsy specimens from 252 patients over a 10-year period. The biopsy findings were compared to those in subsequent biopsy and/or resection specimens. Of the 318 biopsy cases, 104 (32.7 %) cases were diagnosed as adenoma (96 with low-grade dysplasia; 8 with high-grade dysplasia), 19 (6.0 %) adenocarcinomas (ampullary-12, distal bile duct-6, pancreatic-1), 5 (1.6 %) other carcinomas/tumors, and the rest were benign findings (unremarkable, ulcer and acute inflammation, reactive changes, and rare atypical cells/gland). Of the 90 cases with follow-up specimens, 55 cases (61.1 %) had concordant results and 35 (38.9 %) were discordant. Eight (22.9 %) of the 35 discordant cases had major discrepancies (benign biopsy diagnosis with malignant resection diagnosis); 27 (77.1 %) cases had minor discrepancies (normal, reactive, atypical, and dysplastic). We found that vast majority of the false negative biopsy results were due to sampling limitations. Combined biopsy and cytology specimens may help decrease the false negative rate. Careful correlation with endoscopic/cytology/clinical findings and acknowledging the limitation of the biopsy material in the pathology report are important, when malignancy is suspected but cannot be established in a small ampullary biopsy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

During the postoperative follow-up for adrenal tumor for a 78-year-old male patient, a contrast-enhanced computed tomography scan revealed wall thickness with contrast effect in the cystic duct, enlarged lymph nodes along the ileocecal artery, and nodal shadow in the lower lobe of the left lung. First, the collected bile juice at ERC was submitted to cytology multiple times however, no malignant findings were noted. Next, a staging laparoscopy was performed; but the pathological findings of the enlarged lymph nodes and the abdominal lavage cytology showed no malignancy. A nodule in the lower lobe of the left lung was resected for diagnostic and therapeutic purposes, and the pathological diagnosis was primary adenocarcinoma of the lung. Finally the patient underwent exploratory laparotomy for diagnostic purposes. An intraoperative ultrasound- guided needle biopsy for mass lesion located in the medial section of the left liver was performed, and malignant lymphoma was suspected by the intraoperative pathological diagnosis. Cholecystectomy was performed to confirm the histological type, leading to the diagnosis of diffuse large B cell lymphoma. After surgery, the patient underwent 6 courses of rituximab plus CHOP therapy, and the bile duct stricture was improved.

Objectives: Cholestatic liver diseases are characterized by hepatocellular damage, cholangiocyte proliferation, and progressive fibrosis. Bile duct ligation (BDL) is widely used to resemble liver injuries induced by cholestasis. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) was reported to play a critical role in multiple biological responses. Nevertheless, whether PGC1α is involved in bile acid metabolism and biliary disorders remains unclear. This study aimed to investigate the effect of PGC1α on hepatic responses after cholestatic injury., Materials and Methods: Wild-type mice were subjected to BDL or sham surgery for 14 days and human liver specimens from patients with primary biliary cholangitis (PBC) were collected to detect the expression of PGC1α. Hepatic-specific PGC1α knockout mice (HKO) were constructed and subjected to BDL, in which the effects of PGC1α on cholestatic liver injury were demonstrated by biochemical and histopathological assessments, immunoblotting, and metabolomics., Results: The expression of PGC1α was upregulated in the liver of PBC patients and murine models. Both in vivo and in vitro experiments supported the protective effects of PGC1α on cholestasis-induced hepatocyte injury. Infiltrated inflammatory cells after BDL were decreased in HKO mice. Inhibited Wnt/β-Catenin pathway and enhanced Notch signaling promoted transdifferentiation of hepatic progenitor cells (HPC)/ hepatocytes into cholangiocytes, leading to the greater ductular reaction observed in the HKO mice. But bile acids metabolism and mitochondrial function were not affected due to hepatic PGC1α deficiency in cholestasis., Conclusions: Hepatic-specific deletion of PGC1α regulated liver regeneration by promoting ductular reactions, thereby exerting protective effects against BDL-induced liver injury, which could be a new potential therapeutic target., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objectives: Malignant biliary stricture is a ductal narrowing of the bile duct that is often diagnosed at an advanced stage, leading to difficulty in resection. The current study aims to evaluate the feasibility of endobiliary laser treatment by quantifying the extent of coagulative necrosis in tissue under various conditions., Methods: Ex vivo and in vivo porcine bile tissues were used for endobiliary laser treatment to characterize the dosimetric responses of the tissue to various treatment conditions: power level, irradiation time, and number of treatments. 532 nm laser light was coupled with a balloon-integrated diffusing applicator (BDA) to deliver the laser light endoscopically for tissue coagulation. The coagulated regions (maximum length and depth) in the treated tissues were evaluated histologically for quantitative comparison., Results: Dosimetric evaluations with ex vivo liver tissue confirmed that both maximum length and depth of coagulative necrosis (CN) increased with applied power and number of treatments. Ex vivo bile duct tests demonstrated that BDA-assisted laser treatment at 10 W for 12 s reproducibly yielded CN with a length of 5.8 ± 1.6 mm and a depth of 0.6 ± 0.2 mm. In vivo tests presented that endoscopic laser treatment using the BDA created CN on the ductal surface without any perforation. Microscopic examinations revealed that a dense inflammatory cell infiltration and eosinophilic area in the in vivo treated tissue. The extent of CN in the in vivo tissue was 40% longer and 120% deeper (length: 8.1 ± 0.7 mm; depth: 1.3 ± 0.2 mm), compared to that in the ex vivo tissue., Conclusion: BDA-assisted laser treatment could be a feasible option for endoscopic treatment of biliary stricture with uniform ablation at the circumference of bile duct. Further in vivo studies will be performed in a large number of stricture-developed porcine models to examine both efficacy and safety of the proposed endobiliary laser treatment for clinical translations., (© 2023 Wiley Periodicals LLC.)

Context.—: Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized., Objective.—: To investigate their morphologic, immunohistochemical, and molecular features., Design.—: Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing., Results.—: The mean age at diagnosis was 69 years (42-81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%)., Conclusions.—: Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous., (© 2023 College of American Pathologists.)

We report a combination therapy to successfully treat a patient with Hodgkin's lymphoma complicated by vanishing bile duct syndrome. Our patient was in his 20s and presented with jaundice, emesis, B symptoms and diffuse lymphadenopathy along with cholestatic liver injury prompting a liver biopsy, which revealed this diagnosis, after the exclusion of other aetiologies. Our treatment regimen incorporated brentuximab along with other more conventional agents which attempted to maximise therapeutic efficacy while minimising the consequences of hepatotoxicity on the treatment protocol. Although this patient's treatment course was complicated because of neutropenic infections, the patient achieved a complete metabolic response and is now more than 1 year off therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the prognostic significance of microscopic bile duct invasion (MiBDI) in hepatocellular carcinoma (HCC) following R0 resection., Patients and Methods: Patients who underwent R0 resection for HCC at nine medical centers were stratified into five groups: neither bile duct nor vascular invasion (MiBDI-MVI-), microscopic bile duct invasion alone (MiBDI+MVI-), both microscopic bile duct and vascular invasion (MiBDI+MVI+), microscopic vascular invasion alone (MiBDI-MVI+), and macroscopic bile duct invasion (MaBDI). Overall survival (OS) was assessed using Kaplan-Meier analysis, and independent risk factors of OS were determined using Cox proportional hazards models., Results: A total of 377 HCC cases were analyzed. The OS for MiBDI+MVI- was similar to that of MiBDI-MVI- (p > 0.05) but better than MiBDI+MVI+, MiBDI-MVI+, and MaBDI (all p < 0.05). Multivariate analysis indicated that MiBDI was not an independent risk factor for OS, while MVI and MaBDI were., Conclusions: Overall survival (OS) in patients with MiBDI was superior to those with MVI and MaBDI. Isolated MiBDI did not influence OS in patients with HCC after R0 resection., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Biliary stents have been widely used to treat both malignant and benign biliary obstruction. Biliary stenting serves as a temporary measure to maintain ductal patency and promote bile drainage. Biliary decompression can help relieve clinical symptoms of pain, obstructive jaundice, pruritis, fat malabsorption, and failure to thrive and prevent disease progression, such as secondary biliary cirrhosis and end-stage liver failure. Endoscopic placement of biliary endoprosthesis is a minimally invasive procedure well tolerated by most patients but is not without problems. Multiple early and late complications have been reported in the literature and Computed Tomography (CT) is the most used modality to assess normal positions and evaluate patients suspected of stent complications. The aim of this article is to provide a review various of biliary stent related complications, as seen on CT. Current literature on risk factors, diagnosis and management is also discussed., Competing Interests: Declaration of competing interest None. The authors declare that they have no conflicting interests and have not been supported or funded by any drug company or authority., (Copyright © 2023 Elsevier Inc. All rights reserved.)

An 11-year-old female Collie presented with a significantly increased abdominal circumference. Computed tomography of the abdomen revealed that the left lateral lobe of the liver contained a large mass, which was excised via laparotomy. Histologically, many small, dilated, cystic luminal structures were anastomosed and connected to a net-like structure. Immunohistochemistry revealed cytokeratin 19-immunopositive areas, representing bile duct structures in the cystic lumen. Based on these results, the tumour was diagnosed as a bile duct hamartoma. To our knowledge, this is the first report of a bile duct hamartoma in a dog., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The pancreaticobiliary junction (PBJ) stands as a pivotal "hub" where the bile and pancreatic ductsmerge, directing the flow rate and direction of bile and pancreatic juice. Benign pancreaticobiliary junction diseases(BPBJD) can lead to compromised outflow of bile and pancreatic secretions, resulting in elevated pressures within the bile and pancreatic ducts, causing ductal dilation, secretion stasis, and stone formation.Furthermore, BPBJD can shift the direction of bile and pancreatic juice, inducing pancreaticobiliary reflux, bile-pancreatic reflux, or enterobiliary reflux, thereby causing both acute and chronic inflammation and tumors in the biliopancreatic system. Owing to the unique anatomical position of the PBJ and the often intricate and elusive symptoms of benign diseases in this region, clinicians might mainly address standard biliary and pancreatic diseases, overlooking the primary issues associated with the PBJ.Such oversight can yield less-than-optimal clinical outcomes. In response to this, the Gallbladder-Preserving Surgery Committee, Endoscopy Specialist Branch of Chinese Medical Doctor Association and the editorial board of the National Medical Journal of China assembled renowned domestic experts from the fields of hepatobiliary and pancreatic surgery and digestive endoscopy. Drawing upon the latest domestic and international research findings, as well as the clinical expertise of specialists from related fields within China, they have collaboratively developed an expert consensus on the endoscopic diagnosis and treatment of BPBJD. The overarching aim is to propagate and standardize the diagnosis and treatment approaches for BPBJD.

Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies., Competing Interests: Conflict-of-interest statement: The authors declare having no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO 3 - ) buffer system "biliary HCO 3 - umbrella". The impaired production and entry of HCO 3 - from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Cholestasis should be relieved by biliary drainage prior to major liver resection. This condition is often associated with bacterial colonization of the otherwise sterile biliary system. Cholangitis reduces the regenerative capacity of the remaining liver. Therefore, targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma (pCCC)., Methods: Between December 1999 and December 2017, 251 pCCC patients were treated in our center. In total, 115 patients underwent a microbiological analysis. In addition to the characterization of the specific microorganisms and antibiotic resistance, we analyzed subgroups according to preoperative intervention., Results: Enterococci (87/254, 34%) and Enterobacteria (65/254, 26%) were the most frequently detected genera. In 43% (50/115) of patients, Enterococcus faecalis was found in the bile duct sample. Enterococcus faecium (29/115) and Escherichia coli (29/115) were detected in 25% of patients. In patients with percutaneous transhepatic biliary drainage (3/8, 38%) or stents (24/79, 30%), Enterococcus faecium was diagnosed most frequently (P < 0.05). Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012 (P < 0.05). With regard to fungal colonization, the focus was on various Candida strains, but these strains generally lacked resistance., Conclusions: pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention. Specifically, targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection. In our cohort, the combination of meropenem and vancomycin represents an effective perioperative medical approach., (Copyright © 2022. Published by Elsevier B.V.)

Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest.

Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to limited understanding and lack of effective therapeutic strategies. Genetic and epigenetic alterations accumulated in CCA cells can cause the aberrant regulation of oncogenes and tumor suppressors. Epigenetic alterations with histone modification, DNA methylation, and noncoding RNA modulation are associated with the carcinogenesis of CCA. Mutation or silencing of genes by various mechanisms can be a frequent event during CCA development. Alterations in histone acetylation/deacetylation at the posttranslational level, DNA methylation at promoters, and noncoding RNA regulation contribute to the heterogeneity of CCA and drive tumor development. In this review article, we mainly focus on the roles of epigenetic regulation in cholangiocarcinogenesis. Alterations in epigenetic modification can be potential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The length of conventional single-use cholangioscopes poses a challenge for percutaneous or laparoscopic approaches for direct visualization of the biliary tract. The aim of this retrospective observational clinical study was to assess the use of a dedicated percutaneous short single-operator cholangioscope (PSSOC) for diagnosis and treatment of benign or malignant biliary diseases., Methods: Retrospective analysis of a prospectively maintained database including all consecutive patients undergoing percutaneous transhepatic cholangioscopy with the PSSOC between 06/2021 and 01/2023., Results: Forty patients were included (22F/18 M, age 58.7 ± 16.7 years). The diagnostic and therapeutic management plan was based on procedural findings. Indications were bile duct obstruction associated with complex anatomy (n = 13), choledocholithiasis (n = 11), suspected malignant stenosis of the biliary tract (n = 11), biliary stent placement (n = 2) and removal (n = 1), and failed endoscopic retrograde cholangiopancreatography (n = 2). The cholangioscopies were diagnostic (n = 5), therapeutic (n = 20) or both simultaneously (n = 15). The most frequent procedures were electrohydraulic lithotripsy (n = 25) and biopsy sampling (n = 12). Complications occurred in 7 cases (17.5%), including cholangitis (n = 4, B2), pleural perforation (n = 1, B2), portal bleeding (n = 1, B3), and Tako-Tsubo syndrome (n = 1, B3), classified according to the Society of Interventional Radiology classification. Intraprocedural visual diagnosis was confirmed by the histopathologic result in 11/12 patients in which biopsies were performed (91.7%). PSSOC was relevant to avoid surgery in 2 patients (5%) with indeterminate strictures, allowing to rule out malignancy and treat the lithiasis., Conclusions: Direct visualization of the biliary tract enabled targeted biopsies for histopathological diagnosis. The visual and histopathological diagnoses were concordant in all but one case. Percutaneous cholangioscopy with a dedicated PSSOC allows to optimize identification and treatment of complex biliary disease including biliary lithiasis while assessing bile duct patency. The clinical use of the novel PSSOC system was safe and effective and could prevent surgical exploration in select patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The pathogenesis of liver fibrosis in biliary atresia (BA) is unclear. Epidermal growth factor (EGF) plays a vital role in liver fibrosis. This study aims to investigate the expression of EGF and the mechanisms of its pro-fibrotic effects in BA., Methods: EGF levels in serum and liver samples of BA and non-BA children were detected. Marker proteins of EGF signaling and epithelial-mesenchymal transition (EMT) in liver sections were evaluated. Effects of EGF on intrahepatic cells and the underlying mechanisms were explored in vitro. Bile duct ligation (BDL) mice with/without EGF antibody injection were used to verify the effects of EGF on liver fibrosis., Results: Serum levels and liver expression of EGF elevated in BA. Phosphorylated EGF receptor (p-EGFR) and extracellular regulated kinase 1/2 (p-ERK1/2) increased. In addition, EMT and proliferation of biliary epithelial cells were present in BA liver. In vitro, EGF induced EMT and proliferation of HIBEpic cells and promoted IL-8 expression in L-02 cells by phosphorylating ERK1/2. And EGF activated LX-2 cells. Furthermore, EGF antibody injection reduced p-ERK1/2 levels and alleviated liver fibrosis in BDL mice., Conclusion: EGF is overexpressed in BA. It aggravates liver fibrosis through EGF/EGFR-ERK1/2 pathway, which may be a therapeutic target for BA., Impact: The exact pathogenesis of liver fibrosis in BA is unknown, severely limiting the advancement of BA treatment strategies. This study revealed that serum and liver tissue levels of EGF were increased in BA, and its expression in liver tissues was correlated with the degree of liver fibrosis. EGF may promote EMT and proliferation of biliary epithelial cells and induce IL-8 overexpression in hepatocytes through EGF/EGFR-ERK1/2 signaling pathway. EGF can also activate HSCs in vitro. The EGF/EGFR-ERK1/2 pathway may be a potential therapeutic target for BA., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a relatively rare disease and is known as one of the premalignant lesions in the biliary tract. The concept of IPNB has changed through numerous studies and is still evolving. As a lesser studied clinical entity compared with its pancreatic counterpart, intraductal papillary mucinous neoplasm, IPNB has been described in many similar terms, including biliary papillomatosis, biliary intraductal papillary-mucinous neoplasm, and papillary cholangiocarcinoma. This is based on the diversity of histopathological spectrum of IPNB., Methods: This review investigated previous studies including original articles, case studies, and expert opinions. Recently, two types of IPNB (types 1 and 2) have been proposed and validated based on the content first established in the WHO 2010 criteria., Results: This review provides a comprehensive analysis of existing literature, summarizing the clinical, radiological, morphological, and pathological characteristics of IPNB., Conclusion: Given the ongoing ambiguity and controversies surrounding IPNB, future research, including large population-based studies and molecular investigations, is essential to enhance understanding of this disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma., Methods: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses., Results: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance., Conclusion: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Background and Aims: Pathologic evaluation of bile duct lesions is crucial for a definitive diagnosis and determination of an appropriate therapeutic strategy; however, current methods are limited by several challenges. This study evaluated the impact of a novel tapered-tip sheath system on biliary stricture diagnosis., Methods: This observational study evaluated 47 consecutive patients who underwent transpapillary biliary stricture biopsy using the novel tapered-tip sheath system from July 2020 to March 2022 compared with 51 historical control subjects undergoing conventional biopsies. Technical success rate, total biopsy time, number of biopsy specimens, adequate tissue sampling rate, adverse events, and diagnostic performance for biliary strictures were assessed., Results: The technical success rate was favorable in both groups, showing no significant difference (97.9% [46 of 47] vs 88.2% [45 of 51], P = .114). However, the total biopsy time was significantly shorter in the novel system group (3.7 vs 7.7 minutes, P < .001). The number of biopsy specimens did not differ between the groups; however, the novel system group had significantly more cases in which ≥3 tissue samples could be obtained (71.7% [33 of 46] vs 51.1% [23 of 45], P = .043), a higher adequate tissue sampling rate (88.2% vs 66.4%, P < .001), and fewer adverse events (6.4% vs 21.6%, P = .043). Although the diagnostic specificity of both groups was 100%, the novel system group had significantly higher diagnostic sensitivity and accuracy (82.1% vs 50% [P = .004] and 84.8% vs 55.5% [P = .005], respectively)., Conclusions: The novel tapered-tip sheath system is a promising tool for biliary stricture diagnosis., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by the immune-mediated destruction of small and medium intrahepatic bile ducts, involving predominantly females. PBC has long been described as an autoimmune liver disease, also because it is very often associated with many autoimmune conditions. More recently, another pathogenic mechanism exploring the damage of cholangiocytes has been hypothesized, i.e. a defect in the biliary umbrella which is physiologically responsible for the exchange of the ions Cl - and HCO 3 - and maintains the integrity of glycocalyx. To provide a state-of-the-art analysis of this topic, a systematic review of literature in PubMed, Scopus, and Science Direct was conducted (inclusive dates: 1986-2023)., Area Covered: Although the etiology remains unknown, pathogenesis consists of a complex immune-mediated process resulting from a genetic susceptibility. PBC can be triggered by an immune-mediated response to an autoantigen, which leads to a progressive destruction of bile ducts and eventually to a progressive fibrosis with cirrhosis. The defect in the 'bicarbonate umbrella' acts as a protection against the toxic hydrophobic bile acids, leading to a toxic composition of bile., Expert Opinion: This review offers a summary of the current knowledge about the pathogenesis of PBC, indicating that this is probably based on the mutual relationship between the immune insult and the unbalanced secretory mechanisms.

Disturbance in the production and excretion of bile acid causes cholestatic liver disease. Liver cirrhosis is a disease that occurs if cholestasis continues. This study evaluated the protective effect of gallic acid (GA) on liver damage caused by biliary cirrhosis. Rats were randomly divided into 4 groups, each with 8 subjects: 1) control, 2) BDL, 3) BDL + GA 20, and 4) BDL + GA 30. The rats were anesthetized 28 days after the BDL, followed by collecting their blood and excising their liver. Their serum was used to measure liver enzymes, and the liver was used for biochemical analysis, gene expression, and histopathological analysis. Serum levels of liver enzymes, total bilirubin, liver Malondialdehyde level (MDA), expression of inflammatory cytokines and caspase-3, necrosis of hepatocytes, bile duct proliferation, lymphocytic infiltration, and liver fibrosis showed an increase in the BDL group compared to the control group ( p  < 0.05). In addition, BDL decreased the activity of liver antioxidant enzymes and glutathione (GSH) levels compared to the control group ( p  < 0.05). The groups receiving GA indicated a decrease in liver enzymes, total bilirubin, MDA, the expression of inflammatory cytokines and caspase-3, and a reduction in liver tissue damage compared to the BDL group ( p  < 0.05). The level of GSH in the BDL + GA 20 group showed a significant increase compared to the BDL group ( p  < 0.05). Moreover, it was found that GA, with its anti-fibrotic and anti-inflammatory properties, reduces liver damage caused by biliary cirrhosis.

•Intrahepatic biliary proliferations represent a spectrum varying from reactive to malignant entities. •Clinical and imaging patterns may be similar, requiring histopathological and immunohistochemistry for precise diagnosis. Intrahepatic biliary proliferations represent a spectrum from reactive (ductular reaction, some with atypical architecture), hamartomatous (von Meyenburg complex), benign (bile duct adenoma) and precursor/borderline entities (biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct) to fully malignant (cholangiocarcinoma) neoplasms. Clinical pictures and even imaging patterns may be similar, requiring refined studies aiming at histopathological and immunohistochemistry for more precise diagnosis, essential for correct patient management. This article discusses updated concepts and definitions of most relevant entities aiming more specifically at the differential diagnosis in practice, focusing on morphology and immunohistochemistry, with a discussion of potential markers to help distinguishing between benign and malignant lesions.

Background: To clarify the pathological significance of two precursors (high-grade biliary intraepithelial neoplasm [BilIN] and intraductal papillary neoplasm of bile duct [IPNB]) in cholangiocarcinomas (CCAs)., Methods: Ninety-one cases of CCA (47 distal CCAs [dCCAs], 31 perihilar CCAs [pCCAs] and 13 intrahepatic CCAs of large duct type [LD-iCCAs]) were examined for their association with precursors. Neoplastic intraepithelial lesions without underlying infiltrating carcinoma in the surrounding mucosa of CCAs were considered to reflect high-grade BilIN. High-grade BilIN and IPNB were subdivided into gastric, biliary, intestinal and oncocytic subtypes, while CCAs were subdivided into gastrobiliary, intestinal and oncocytic subtypes. The postoperative overall survival (OS) was examined., Results: Fifty-four and 8 of 91 CCAs were associated with high-grade BilIN and IPNB, respectively, while these precursors were unidentifiable in the remaining CCAs. A majority of CCAs were of the gastrobiliary subtype, while the intestinal subtype was occasionally detected, and the oncocytic subtype was rare. CCAs with high-grade BilIN showed a similar postoperative OS to CCAs without precursors, while CCAs with IPNB showed a favorable postoperative OS compared to CCAs without precursors., Conclusions: CCAs were frequently associated with precursors; high-grade BilIN may be a major precursor and IPNB a minor one. CCAs with IPNB showed a favorable postoperative OS compared to CCAs with high-grade BilIN., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Purpose: To assess longitudinal changes in quantitative MRI metrics in pediatric and young adult patients with autoimmune liver disease (AILD)., Methods: This prospective, IRB-approved study included 20 children and young adults (median age = 15 years) with primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC) and 19 (median age = 17 years) with autoimmune hepatitis (AIH). At a field strength of 1.5-T, T2*-corrected T1 mapping (cT1), 3D fast spin-echo MRCP, and 2D gradient recalled echo MR elastography (MRE) were performed at baseline, one year, and two years. cT1 and quantitative MRCP were processed using LiverMultiScan and MRCP + , respectively (Perspectum Ltd, Oxford, UK). Linear mixed models were used to assess longitudinal changes in quantitative MRI metrics. Spearman rank-order correlation was used to assess relationships between changes in quantitative MRI metrics., Results: Changes in quantitative MRI metrics greater than established repeatability coefficients were measured in six (cT1) and five (MRE) patients with PSC/ASC as well as in six patients (cT1 and MRE) with AIH, although linear mixed models identified no significant changes for the subgroups as a whole. For PSC/ASC, there were positive correlations between change in liver stiffness and changes in bile duct strictures (ρ = 0.68; p = 0.005) and bile duct dilations (ρ = 0.70; p = 0.004) between baseline and Year 2., Conclusion: On average, there were no significant changes in quantitative MRI metrics over a two-year period in children and young adults with AILD. However, worsening cholangiopathy was associated with increasing liver stiffness by MRE in patients with PSC/ASC., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The biliary epithelial cells, also known as cholangiocytes, line the intra- and extrahepatic bile ducts, forming a barrier between intra- and extra-ductal environments. Cholangiocytes are mostly known to modulate bile composition and transportation. In hepatobiliary diseases, bile duct injury leads to drastic alterations in cholangiocyte phenotypes and their release of soluble mediators, which can vary depending on the original insult and cellular states (quiescence, senescence, or proliferation). The cholangiocyte-secreted cytokines (also termed cholangiokines) drive ductular cell proliferation, portal inflammation and fibrosis, and carcinogenesis. Hence, despite the previous consensus that cholangiocytes are bystanders in liver diseases, their diverse secretome plays critical roles in modulating the intrahepatic microenvironment. This review summarizes recent insights into the cholangiokines under both physiological and pathological conditions, especially as they occur during liver injury-regeneration, inflammation, fibrosis and malignant transformation processes., Competing Interests: Author FT’s lab received research grants from Gilead, Allergan, Bristol-Myers Squibb and Inventiva. The remaining 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 © 2023 Cai, Tacke, Guillot and Liu.)

A 72-year-old woman was referred for the examination of wall thickening of the bile duct and a polyp-like lesion on the gallbladder. The bile duct and gallbladder lesions were observed to be continuous on abdominal ultrasonography. We performed a bile duct biopsy, and pathological findings showed hyperplasia of the lymphoid follicles without malignancy. We considered these two lesions to be the same lesion, and laparoscopic cholecystectomy was performed to make a definite diagnosis. The pathological examination of the resected gallbladder also showed hyperplasia of the lymphoid follicles. We diagnosed the patient with lymphoid hyperplasia of the gallbladder extending to the bile duct.

Background and Aims: Indirect diagnostic modalities are unsatisfactory for detecting intraductal neoplasm of the bile duct (IN-B), which can be detected by peroral cholangioscopy (POC) with narrow-band imaging (NBI). We investigated the POC findings of IN-B and developed a feasible endoscopic classification system., Methods: Four hundred seventy-one patients who underwent direct POC from April 2008 to July 2020 were enrolled. Intraductal superficial lesions of the bile duct (ISL-Bs) were classified according to surface structure and microvascular pattern on POC with NBI and correlated to histologic findings after POC-guided forceps biopsy sampling (POC-FB) or surgery. The primary outcome was the detection rate of IN-Bs, and the secondary outcomes were the associations of POC findings with IN-B, technical success rates of POC and POC-FB, and adverse events., Results: Direct POC was successful in 458 of 471 patients (97.2%). Among the patients, 131 (27.8%) exhibited ISL-Bs. The technical success rate of POC-FB was 94.7% (124/131). Among the 124 patients who underwent POC-FB, IN-B was revealed in 54 (43.5%), for a detection rate of 11.8% (54/458). Papillary lesions (P = .041), nodular lesions (P = .044), and irregularly or regularly dilated and tortuous vessels (P = .004 and P = .006, respectively) were POC findings associated with IN-B. The area under the receiver-operating characteristic curve of the novel classification system was .899., Conclusions: POC with NBI can be useful for the detection of IN-Bs. Our novel classification system based on both surface structure and microvascular pattern may allow differentiation of IN-B from ISL-Bs., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Drug-induced bile duct injury is a specific kind of drug-induced liver injury that has two main pathological types, namely ductopenia, or vanishing bile duct syndrome, and secondary sclerosing cholangitis. However, in recent years, the reports of new drugs that cause bile duct injury have been constantly increasing, and these drugs have different clinicopathological features and a novel pathogenesis. Therefore, this paper summarizes and analyzes the progress and challenges in the etiology, pathogenesis, diagnosis and treatment, and other aspects of drug-induced bile duct injury.

Introduction: Bile duct ligation (BDL) and subsequent cholestasis are associated with oxidative stress and liver injury and fibrosis. Hesperidin (3,5,7-trihydroxyflavanone 7-rhamnoglucoside) is a flavanone glycoside abundant in citrus fruits. It has positive effects on diabetic retinopathy, reduced platelet aggregation, and blood flow alterations and has the potential to reduce liver injury in oxidative stress. The aim of this study was to evaluate the hepatoprotective effects of hesperidin on BDL-induced liver injury in rats., Methods: A total of 48 adult male Wistar rats were equally allocated to six eight-rat groups, namely, a healthy group, a sham group, a BDL+Vehicle group (BDL plus treatment with distilled water), a BDL+VitC group (BDL plus treatment with vitamin C 4.25  μ g/kg), a BDL+Hesp100 group (BDL plus treatment with hesperidin 100 mg/kg/day), and a BDL+Hesp200 group (BDL plus treatment with hesperidin 200 mg/kg/day). Treatments were orally provided for 21 consecutive days. Finally, rats were sacrificed through heart blood sampling. Blood samples were centrifuged, and liver function, oxidative stress, and antioxidant parameters were assessed. Liver tissue was also assessed for oxidative stress, antioxidant, and histological parameters. The expression of inflammatory genes, namely, TGF β 1, iNOS, Caspase-3, and α -SMA, was measured through polymerase chain reaction. Findings . Hesperidin supplementation was associated with significant decrease in the levels of liver enzymes, bilirubin, nitric oxide, malondialdehyde, protein carbonyl, and inflammatory gene expression; significant increase in the levels of total antioxidant capacity, glutathione, and superoxide dismutase and catalase enzyme activity; and significant improvement in the histological morphology and structure of the liver parenchyma., Conclusion: Hesperidin has significant positive effects on liver morphology and structure, inflammation, fibrosis, and oxidative stress in rats with BDL-induced cholestatic liver injury., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Zahra Nasehi et al.)

The "Gut-Liver Axis" refers to the physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of a change in gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions cause cholangiocytes to be exposed to an increasing amount of microorganisms that can reactivate inflammatory responses, thus inducing the onset of liver fibrosis. The present review focuses on the role of the gut-liver axis in the pathogenesis of cholangiopathies.

Background/purpose: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers., Methods: A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days., Results: A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 ( P =0.016), intrahepatic versus extrahepatic tumor ( P =0.027), single versus multiple tumors ( P =0.007), those who underwent hepatic versus pancreatic resection ( P =0.017), or achieved versus failed TO ( P =0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P =0.03) was an independent prognostic factor of poor overall survival., Conclusions: Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Biliary atresia is a potentially fatal condition of the bile ducts - both intra- and extrahepatic, for which we have no cure. Though principally a cholestatic condition, much of its pathology stems from its tendency to aggressively induce liver fibrosis and ultimately cirrhosis, only partially restrained by the portoenterostomy., Areas Covered: This review is based on the current literature exploring the heterogeneous nature of biliary atresia. Thus, there are various phenotypes or variants of biliary atresia, each potentially with different etiological backgrounds caused by a number of hypothetical pathological mechanisms thought to be important in the genesis of the condition. Search methodology: the review (Oct. - Nov. 2022) is based on a search of PubMed (NLM) using main keyword 'biliary atresia' with supplementary searches using 'fibrosis'; 'inflammation'; 'BASM'; 'genetics'; 'surgery'; 'experimental'; 'etiology'; 'virology'; 'cases'; and 'syndromes.', Expert Opinion: Future developments will be made on matching clinical variants with a more distinct pathophysiological discrimination and those pathways linking the initial cholestatic phase of biliary atresia to the early stages of fibrosis.

Background & Aims: Accumulating evidence suggest that Hippo-yes-associated protein (YAP) pathway plays important roles in development and repair after injuries in biliary system. We disclosed that senescent biliary epithelial cells (BECs) participate in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that dysregulation of Hippo-YAP pathway may be associated with biliary epithelial senescence in pathogenesis of PBC., Approach & Results: Cellular senescence was induced in cultured BECs by treatment with serum depletion or glycochenodeoxycholic acid. The expression and activity of YAP1 were significantly decreased in senescent BECs (p<0.01). Cellular senescence and apoptosis were significantly increased (p<0.01) and a proliferation activity and a 3D-cyst formation activity were significantly decreased (p<0.01) by a knockdown of YAP1 in BECs. The expression of YAP1 were immunohistochemically determined in livers taken from the patients with PBC (n = 79) and 79 control diseased and normal livers and its association with senescent markers p16 INK4a and p21 WAF1/Cip1 was analyzed. The nuclear expression of YAP1, which indicates activation of YAP1, was significantly decreased in BECs in small bile ducts involved in cholangitis and ductular reactions in PBC, compared to control livers (p<0.01). The decreased expression of YAP1 was seen in senescent BECs showing expression of p16 INK4a and p21 WAF1/Cip1 in bile duct lesions., Conclusion: Dysregulation of Hippo-YAP1 pathway may be involved in the pathogenesis of PBC in association with biliary epithelial senescence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)