Determining the patency of biliary tracts in dogs with gallbladder mucocele using near-infrared cholangiography with indocyanine green.

Cholecystectomy is indicated for gallbladder mucoceles (GBM). Evaluating the patency of the biliary duct and precise biliary tree visualization is crucial for reducing the risk of compromised bile flow after surgery. Therefore, intraoperative cholangiography (IOC) is recommended during cholecystectomy to prevent biliary tract injury. Although indocyanine green (ICG) cholangiography has been extensively reported in human medicine, only one study has been conducted in veterinary medicine. Therefore, this study aimed to demonstrate the use of ICG for IOC to identify fluorescent biliary tract images and determine the patency of the common bile duct during cholecystectomy in dogs. This study comprised 27 dogs, consisting of 17 with gallbladder mucoceles (GBM) and 10 controls, specifically including dogs that had undergone elective cholecystectomy for GBM. ICG injection (0.25 mg/kg) was administered intravenously at least 45 minutes before surgery. During the operation, fluorescent images from cholangiography were displayed on the monitor and obtained in black-and-white mode for the comparison of fluorescence intensity (FI). The FI values of the gallbladders (GBs) and common bile duct (CBD) were measured using FI analyzing software (MGViewer V1.1.1, MetapleBio Inc.). The results demonstrated successful CBD patency identification in all cases. Mobile GBM showed partial gallbladder visibility, whereas immobile GBM showed limited visibility. Additionally, insights into the adequate visualization of the remaining extrahepatic biliary tree anatomy were provided, extending beyond the assessment of CBD patency and gallbladder intensity. Our study demonstrates the potential of fluorescent IOC using intravenous injection of ICG for assessing the patency of the cystic duct and common bile duct during cholecystectomy in patients with GBM, eliminating the need for surgical catheterization and flushing of the biliary ducts. Further research is warranted to investigate and validate the broader applicability of ICG cholangiography in veterinary medicine.

Intestinal microbiota and biliary system diseases.

Introduction: The incidence of biliary system diseases has been continuously increasing in the past decade. Biliary system diseases bring a heavy burden to humanity and society. However, the specific etiology and pathogenesis are still unknown. The biliary system, as a bridge between the liver and intestine, plays an indispensable role in maintaining the physiological metabolism of the body. Therefore, prevention and treatment of biliary diseases are crucial. It is worth noting that the microorganisms participate in the lipid metabolism of the bile duct, especially the largest proportion of intestinal bacteria. Methods: We systematically reviewed the intestinal microbiota in patients with gallstones (GS), non-calculous biliary inflammatory, and biliary tract cancer (BTC). And searched Pubmed, Embase and Web of science for research studies published up to November 2023. Results: We found that the abundance of Faecalibacterium genus is decreased in GS, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and BTC. Veillonella, Lactobacillus, Streptococcus and Enterococcus genus were significantly increased in PSC, PBC and BTC. Interestingly, we found that the relative abundance of Clostridium was generally reduced in GS, PBC and BTC. However, Clostridium was generally increased in PSC. Discussion: The existing research mostly focuses on exploring the mechanisms of bacteria targeting a single disease. Lacking comparison of multiple diseases and changes in bacteria during the disease process. We hope to provide biomarkers forearly diagnosis of biliary system diseases and provide new directions for the mechanism of intestinal microbiota in biliary diseases.

The dysregulation of biliary tract microflora is closely related to primary choledocholithiasis: a multicenter study.

Bile microecology changes play an important role in the occurrence and development of choledocholithiasis. At present, there is no clear report on the difference of bile microecology between asymptomatic patients with gallbladder polyps and choledocholithiasis. This study compared bile microecology between gallbladder polyp patients and patients with choledocholithiasis to identify risk factors for primary choledocholithiasis. This study was conducted in 3 hospitals in different regions of China. Bile samples from 26 patients with gallbladder polyps and 31 patients with choledocholithiasis were collected by laparoscopic cholecystectomy and endoscopic retrograde choledocholithiasis cholangiography (ERCP), respectively. The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. The α-diversity of bile microecological colonies was similar between gallbladder polyp and choledocholithiasis, but the ß-diversity was different. Firmicutes, Proteobacteri, Bacteroidota and Actinobacteriota are the most common phyla in the gallbladder polyp group and choledocholithiasis group. However, compared with the gallbladder polyp patients, the abundance of Actinobacteriota has significantly lower in the choledocholithiasis group. At the genera level, the abundance of a variety of bacteria varies between the two groups, and Enterococcus was significantly elevated in choledocholithiasis group. In addition, bile biofilm formation-Pseudomonas aeruginosa was more metabolically active in the choledocholithiasis group, which was closely related to stone formation. The analysis of metabolites showed that a variety of metabolites decreased in the choledocholithiasis group, and the concentration of beta-muricholic acid decreased most significantly. For the first time, our study compared the bile of gallbladder polyp patients with patients with choledocholithiasis, and suggested that the change in the abundance of Actinobacteriota and Enterococcus were closely related to choledocholithiasis. The role of Pseudomonas aeruginosa biofilm in the formation of choledocholithiasis was discovered for the first time, and some prevention schemes for choledocholithiasis were discussed, which has important biological and medical significance.

Liver transplant for primary biliary tract neuroendocrine tumor in a nine-year-old girl.

BACKGROUND: Neuroendocrine tumors (NETs) are rare epithelial neoplasms that arise most commonly from the gastrointestinal tract. In pediatrics, the most common site of origin is in the appendix, with the liver being the most common site of metastasis. Neuroendocrine tumors arising from the biliary tract are extremely rare. METHODS: We describe a case of a nine-year-old girl who presented with obstructive cholestasis and was found to have multiple liver masses identified on biopsy as well-differentiated neuroendocrine tumor with an unknown primary tumor site. RESULT: The patient underwent extensive investigation to identify a primary tumor site, including endoscopy, endoscopic ultrasound, and capsule endoscopy. The patient ultimately underwent definitive management with liver transplant, and on explant was discovered to have multiple well-differentiated neuroendocrine tumors, WHO Grade 1, with extensive infiltration into the submucosa of bile duct, consistent with primary biliary tract neuroendocrine tumor. CONCLUSION: Identifying the site of the primary tumor in NETs found within the liver can be challenging. To determine if an extrahepatic primary tumor exists, workup should include endoscopy, EUS, and capsule endoscopy. Children with well-differentiated hepatic NETs, with no identifiable primary tumor, and an unresectable tumor, are considered favorable candidates for liver transplantation.

Features of biliary tract diseases in ketamine abusers: a systematic review of case reports.

BACKGROUND AND AIMS: Anesthesiologists prefer ketamine for certain surgeries due to its effectiveness as a non-competitive inhibitor of the N-methyl-D-aspartate receptor in the brain. Recently, this agent has also shown promise as an antidepressant. However, ketamine can cause hallucinogenic effects and is sometimes abused as an illicit drug. Ketamine abuse has been associated with liver and bile duct complications. This systematic study aims to better understand cholangiopathy in ketamine abusers by reviewing case reports. METHODS AND MATERIAL: In this systematic review, a comprehensive literature search was conducted with the terms "biliary tract diseases" and "ketamine". Case reports and case series of adult patients with documented ketamine abuse and reported cholangiopathy or biliary tract disease were included. We extracted the data of relevant information and the results were reported through narrative synthesis and descriptive statistics. RESULTS: A total of 48 studies were initially identified, and 11 studies were finally included in the review. The mean age of the patients was 25.88 years. Of the 17 patients, 64.7% were men. Symptoms often included abdominal pain, nausea, and vomiting. Most patients were discharged with improved symptoms and liver function. Common bile duct dilation and other findings were observed in imaging results and other diagnostic studies. CONCLUSION: This review highlights the diverse presentations and diagnostic modalities used in ketamine-induced cholangiography. These patients tend to be young men with deranged liver function tests and abdominal pain, which should be taken into consideration. These patients often require a multidisciplinary approach in their management.

Proteomic analysis of serum extracellular vesicles from biliary tract infection patients to identify novel biomarkers.

Biliary tract infection (BTI), a commonly occurring abdominal disease, despite being extensively studied for its initiation and underlying mechanisms, continues to pose a challenge in the quest for identifying specific diagnostic biomarkers. Extracellular vesicles (EVs), which emanate from diverse cell types, serve as minute biological entities that mirror unique physiological or pathological conditions. Despite their potential, there has been a relatively restricted exploration of EV-oriented methodologies for diagnosing BTI. To uncover potent protein biomarkers for BTI patients, we applied a label-free quantitative proteomic method known for its unbiased and high-throughput nature. Furthermore, 192 differentially expressed proteins surfaced within EVs isolated from individuals afflicted with BTI. Subsequent GO and KEGG analyses pinpointed Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and Crumbs homolog 3 (CRB3) as noteworthy biomarkers. Validation via data analysis of plasma-derived EV samples confirmed their specificity to BTI. Our study leveraged an unbiased proteomic tool to unveil CEACAM1 and CRB3 as promising protein biomarkers in serum EVs, presenting potential avenues for the advancement of diagnostic systems for BTI detection.

Short-term clinical outcomes of percutaneous biliary tract interventions: analysis of success and complication rates.

INTRODUCTION: Obstructive jaundice is a clinical syndrome that is commonly seen in gastroenterology. Endoscopic retrograde cholangiopancreatography (ERCP) has been recognized as a first-choice therapeutic approach, with percutaneous biliary interventions (PBIs) being a viable alternative. Recent data questions the performance and safety profile of PBIs.

A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

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.

LiverZap: a chemoptogenetic tool for global and locally restricted hepatocyte ablation to study cellular behaviours in liver regeneration.

The liver restores its mass and architecture after injury. Yet, investigating morphogenetic cell behaviours and signals that repair tissue architecture at high spatiotemporal resolution remains challenging. We developed LiverZap, a tuneable chemoptogenetic liver injury model in zebrafish. LiverZap employs the formation of a binary FAP-TAP photosensitiser followed by brief near-infrared illumination inducing hepatocyte-specific death and recapitulating mammalian liver injury types. The tool enables local hepatocyte ablation and extended live imaging capturing regenerative cell behaviours, which is crucial for studying cellular interactions at the interface of healthy and damaged tissue. Applying LiverZap, we show that targeted hepatocyte ablation in a small region of interest is sufficient to trigger local liver progenitor-like cell (LPC)-mediated regeneration, challenging the current understanding of liver regeneration. Surprisingly, the LPC response is also elicited in adjacent uninjured tissue, at up to 100 µm distance to the injury. Moreover, dynamic biliary network rearrangement suggests active cell movements from uninjured tissue in response to substantial hepatocyte loss as an integral step of LPC-mediated liver regeneration. This precisely targetable liver cell ablation tool will enable the discovery of key molecular and morphogenetic regeneration paradigms.

Novel approach for reconstruction of the three-dimensional biliary system in decellularized liver scaffold using hepatocyte progenitors.

Reconstruction of the biliary system is indispensable for the regeneration of transplantable liver grafts. Here, we report the establishment of the first continuous three-dimensional biliary system scaffold for bile acid excretion using a novel method. We confirmed the preservation of the liver-derived extracellular matrix distribution in the scaffold. In addition, hepatocyte progenitors decellularized via the bile duct by slow-speed perfusion differentiated into hepatocyte- and cholangiocyte-like cells, mimicking hepatic cords and bile ducts, respectively. Furthermore, qRT-PCR demonstrated increased ALB, BSEP, and AQP8 expression, revealing bile canaliculi- and bile duct-specific genetic patterns. Therefore, we concluded that locally preserved extracellular matrices in the scaffold stimulated hepatic progenitors and provided efficient differentiation, as well as regeneration of a three-dimensional continuous biliary system from hepatic cords through bile ducts. These findings suggest that organ-derived scaffolds can be utilized for the efficient reconstruction of functional biliary systems.

Biliary stem cells in health and cholangiopathies and cholangiocarcinoma.

PURPOSE OF REVIEW: This review discusses evidence regarding progenitor populations of the biliary tree in the tissue regeneration and homeostasis, and the pathobiology of cholangiopathies and malignancies. RECENT FINDINGS: In embryogenesis biliary multipotent progenitor subpopulation contributes cells not only to the pancreas and gall bladder but also to the liver. Cells equipped with a constellation of markers suggestive of the primitive endodermal phenotype exist in the peribiliary glands, the bile duct glands, of the intra- and extrahepatic bile ducts. These cells are able to be isolated and cultured easily, which demonstrates the persistence of a stable phenotype during in vitro expansion, the ability to self-renew in vitro, and the ability to differentiate between hepatocyte and biliary and pancreatic islet fates. SUMMARY: In normal human livers, stem/progenitors cells are mostly restricted in two distinct niches, which are the bile ductules/canals of Hering and the peribiliary glands (PBGs) present inside the wall of large intrahepatic bile ducts. The existence of a network of stem/progenitor cell niches within the liver and along the entire biliary tree inform a patho-biological-based translational approach to biliary diseases and cholangiocarcinoma since it poses the basis to understand biliary regeneration after extensive or chronic injuries and progression to fibrosis and cancer.