Intrahepatic Ducts Research Articles

Assessment of variations in intrahepatic bile duct by magnetic resonance cholangiopancreatography

For any biliary system or liver surgery, it is crucial to have a thorough understanding of the normal branching pattern of the intrahepatic bile duct and its deviations in order to prevent serious post-surgical problems and morbidity. Aim: This study's goal was to assess the variations in intrahepatic bile ducts appeared during Magnetic Resonance Cholangiopancreatography (MRCP) examinations. Place and Duration: In the Radiology department of Mian Gul Abdul Haq Jehanzeb Kidney Hospital Swat from January 2022 to June 2022. Methods: This cross-sectional, quantitative study was conducted among people who had been referred for MRCP examinations for a number of clinical reasons. A total of 70 patients done with MRCP examinations were selected by convenience sampling technique being used. The data of 1.5T Magnetom Amira Siemens MRI scanner was used for anlaysis. Using visual analysis, the 3D MRCP images were categorized into 7 Types using the Choi et al classification. Results: Among the 36(51.4%) patients in this analysis had Type 1/normal IHBD, 13(18.6%) had Type 2 IHBD, Type 3A was seen in 2(2.8%), and Type 3B was noticed in 5.7% of subjects.

Use of Barbed Suture During Minimally Invasive Resection of the Choledochal Cyst

Introduction: Choledochal cysts are rare congenital anomalies of the bile ducts, characterized by dilations of the intrahepatic and extrahepatic biliary ducts. Approximately 80% are diagnosed in childhood, with a higher incidence in Asian countries.1 Imaging studies are essential for the diagnosis, including magnetic resonance cholangiopancreatography as the method of choice.2 Patients with types I, II, or IV cysts usually undergo surgical resection of the cysts because of the significant risk of malignancy. The treatment of choice of type I bile duct cysts in adults is total cystectomy and hepaticojejunostomy in a Roux-en-Y manner.2 The advantages of this procedure include a reduced incidence of anastomotic strictures, stone formation, cholangitis, and intracystic malignancy.2 This video shows the surgical steps, tips, and tricks of minimally invasive resection of the choledochal cyst and continuity with a bilioenteric anastomosis. Materials and Methods: A 48-year-old woman with previous laparoscopic cholecystectomy presented with a history of right subcostal pain and jaundice. After magnetic resonance cholangiopancreatography, a type I Todani choledochal cyst was diagnosed with a width of the proximal bile duct of 12 mm. She underwent minimally invasive resection of the bile duct and a terminolateral hepaticojejunostomy in a Roux-en-Y manner. Operatively, an 11 mm trocar was placed at the umbilicus. Three 5 mm trocars were placed in the epigastrium, right hypochondrium, and right flank. An 11 mm trocar was placed in the left flank. A type I choledochal cyst was confirmed with cystic duct dilation. The right hepatic artery, proximal bile duct, and portal vein were identified. The main bile duct was completely dissected, and two clips were placed in the intrapancreatic portion. The distal part of the bile duct was sectioned above the clips. The proximal bile duct was divided 1 cm from the hilar plate and the specimen was completely removed. The jejunal loop was identified and a terminolateral hepaticojejunal anastomosis was performed using barbed suture (V-locTM 4/0, Covidien). Then, a laterolateral jejunojejunal anastomosis was performed using a stapler. The common loop between the two anastomosis was sectioned with another stapler that completed the Roux-en-Y. Finally, a subhepatic suction drain was left. Results: The drain was removed 72 hours after the procedure and the patient was discharged on postoperative day 6 without complications. The pathology report confirmed a choledochal cyst without malignancy. A follow-up was done at 1 and 6 months. The patient was asymptomatic and blood workup and cholangiography were normal. Conclusions: Different publications with high level of evidence document that minimally invasive surgical treatment on Todani I choledochal cysts reduces hospital stay and postoperative pain compared with an open approach.3 It is a demanding technique with a long learning curve that decreases with the use of barbed sutures without increasing complications. No competing financial interests exist. Runtime of video: 10 mins 0 secs

Liver Wound Healing Is Associated with An Increase in Mfge8 Expression in Hepatocytes

Being recognized as a typical pathological feature of liver diseases, apoptosis-induced hepatocyte injury leading to sterile inflammation drives a wound-healing path in vivo. We and other researchers reported that Milk fat globule-EGF factor 8 (MFGE8) preserves tissue homeostasis, protects against tissue injury and inflammation, and attenuates nonalcoholic fatty liver disease and fibrosis. However, it is unclear whether and how MFGE8 is involved in liver regeneration from hepatocyte-apoptosis-induced injury. Our aim is to study current knowledge to this extent, we created a novel triple-transgenic mouse model, an inducible hepatocyte-specific apoptosis phenotype (namely, 3XTg-iHAP), in which the inducible hepatocyte-specific FasL expression is under control of the combined LoxP-Albumin-Cre system and rtTA Tet-On regulatory element. The liver tissues from 3XTg-iHAP and their littermates were collected at 8 h, 24 h, 48 h, 72 h, and 5 D after doxycycline (Dox, 5mg/kg, s.c., single dose) treatment and subjected to histological examination, RNAScope in situ hybridization (ISH) and qRT-PCR analysis. We first confirmed that the 3XTg-iHAP mice developed normal, viable, and fertile. Upon Dox treatment, qRT-PCR confirmed FasL expression was specifically induced in the liver tissues of 3XTg-iHAP mice (male, 7 weeks) but not in their littermates. H&E sections show the induction of hepatocyte apoptosis as early as 24 h followed by apoptosis-induced sterile inflammation and injury, hepatocyte mitosis, and regeneration in the liver parenchyma of 3XTg-iHAP mice. In the ISH assay, we found that (1) In littermate control mice, Mfge8 transcripts were localized in the intrahepatic bile duct epithelial cells (i.e., cholangiocytes) within the portal area. (2) In Dox-treated 3XTg-iHAP mice, we observed a profound increase of Mfge8 gene expression in parenchymal hepatocytes of the liver featured with apoptosis-associated sterile injury. In summary, we validated a novel 3XTg-iHAP mouse liver wound-healing model. The Mfge8 gene is constitutively expressed in the bile duct epithelial cells under the normal physiological condition, while upregulated in hepatocytes in response to the apoptosis-induced injury and repair. Our results suggest that liver wound healing is associated with an increase in Mfge8 expression in hepatocytes. The underlying mechanisms of whether and how MFG-E8 promotes the liver wound healing process need to be further studied. Grants are supported by NIH and the U.S. Department of Veterans Affairs. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need.

Cholangiocarcinoma is a highly aggressive cancer of the biliary tract epithelium. This form of cancer is prevalent in Asia, and recent reports show that its incidence is relatively rare but increasing in the United States. Although risk factors for cholangiocarcinoma have yet to be elucidated, a growing body of literature suggests chronic infection of genetically susceptible individuals with the food-borne zoonotic trematodes Clonorchis sinensis (C sinensis) and Opisthorchis viverrini (O viverrini) may play a role. Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for almost 30 years. During this period, the trematodes' feeding activities and their excretory-secretory products may damage the bile duct epithelium and promote local inflammation. These pathological processes could then provoke epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to the initiation and progression of cholangiocarcinoma in genetically susceptible people. The International Agency for Research on Cancer has determined that there is sufficient evidence in humans for the carcinogenicity of chronic infections with C sinensis and O viverrini. Timely serodiagnosis of indolent C sinensis and O viverrini infections is important as these parasites may be a risk factor for cholangiocarcinoma in veterans who served in Vietnam. About 774,000 living Americans served in Vietnam and there is an urgent need to develop sensitive and specific serologic assays to detect both acute and indolent infections. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival.

Micro-hepatocellular carcinoma with bile duct tumor thrombus mimicking intrahepatic intraductal papillary neoplasm of the bile duct: a case report

BackgroundMicrohepatocellular carcinoma with a gross bile duct tumor thrombus is extremely rare, making the correct preoperative diagnosis difficult.Case presentationA 78-year-old man was referred to our department for close examination of a liver tumor that was incidentally detected using ultrasonography. Blood tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a 2-cm-sized hyperechoic mass with indistinct borders and hypoechoic margins at the origin of the right hepatic duct. Dynamic computed tomography showed a tumor with arterial phase predominance, a heterogeneous contrast effect, and prolonged enhancement. Cystic structures were observed in the tumors. In addition, localized dilatation of the caudate lobe bile duct was observed near the tumor. Cholangiography showed that the common bile duct, right and left hepatic ducts, and secondary branches did not have dilatation or stenosis. Biopsies of the bile duct revealed no malignancy. Under suspicion of intrahepatic intraductal papillary neoplasm of the bile duct, right hemi-hepatectomy was performed. The extrahepatic bile duct was preserved, because no tumor was found at the margin of the right hepatic duct during intraoperative frozen diagnosis. Macroscopically, the lesion was an 18 × 15 mm tumor occupying a dilated intrahepatic bile duct near the right hepatic duct, with a soft, fine papillary tumor. Based on morphology and immunostaining, tumor matched with moderately differentiated hepatocellular carcinoma. In addition, a 2 mm-sized hepatocellular carcinoma was observed in the liver parenchyma near the bile duct, where the tumor was located.ConclusionsBased on these findings, the patient was diagnosed with small hepatocellular carcinoma with a gross bile duct tumor thrombus. The cystic part seen on the preoperative images was considered as a gap between the bile duct and the tumor thrombus. The patient recovered well with no signs of recurrence 20 months after surgery.

Overlap syndrome of primary biliary cholangitis and primary sclerosing cholangitis: two case reports

BackgroundOverlap syndrome between primary biliary cholangitis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only few published cases so far in the literature. We highlight here the rarity of this condition and indicate the importance of its recognition.Case presentationWe report two cases showing the manifestations of both primary biliary cholangitis and primary sclerosing cholangitis in two Tunisian female patients aged 74 and 42 years, respectively. The first case is a woman who was initially diagnosed with decompensated cirrhosis. Magnetic resonance cholangiopancreatography showed multiple strictures of the common bile duct, and histological findings led to the diagnosis of primary biliary cholangitis/primary sclerosing cholangitis. She was successfully treated with ursodeoxycholic acid. The second case is a middle-aged woman, suffering from primary biliary cholangitis and who was treated with ursodeoxycholic acid. At her 12 month follow-up appointment, she presented with a partial clinical and biochemical response. Tests showed normal thyroid function, liver autoimmune tests for autoimmune hepatitis were negative, and celiac disease markers were also negative. The diagnosis of overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis was finally made on the results of magnetic resonance cholangiopancreatography that showed multiple strictures of the common as well as intrahepatic bile ducts. The patient was put on ursodeoxycholic acid at a higher dose.ConclusionsOur cases raise awareness for this rare condition and indicate the importance of recognizing a possible overlap syndrome, especially in patients with primary biliary cholangitis, to optimize treatment. We suggest considering the overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis when a patient presents with the diagnostic criteria of both diseases.

Caroli Syndrome Associated with Polycystic Kidney Disease: A Case Report

Introduction: Caroli disease is a fibrocystic liver disease characterized by congenital nonobstructive cystic dilatation of the intrahepatic bile ducts. Its association with congenital hepatic fibrosis defines Caroli syndrome. The more common Caroli syndrome is associated with cystic renal dilatations in 60-80% of patients with polycystic kidney disease and Cacchi-Ricci disease as the most frequently noted renal anomalies. Objective: We want to define this uncommon entity and to describe the radiological characteristics which can, in the absence of their knowledge, be a source of confusion for the radiologist and pose problems of diagnostic delay. Case Report: The patient was a male infant, 1 year and 10 months old, with a history of 2 episodes of urinary tract infections at the age of 3 months and 6 months, and a 13-year-old sister with polycystic hepatorenal disease. The patient was admitted to the pediatric emergency department for acute fever associated with fluid diarrhea evolving for 3 days and irritability and crying at the time of urination. A cytobacteriological examination of the urine showed a turbid appearance of the urine with isolation of Escherichia Coli on culture. Abdominal ultrasound revealed bilateral nephromegaly, with diffuse microcystic hyperechogenicity of medullary pyramids generating multiple comet tail images with a "sponge kidney" appearance as well as a homogeneous splenomegaly and a normal sized liver of heterogeneous echostructure with cystic dilatation of the intrahepatic bile ducts which are centered by hyperechoic punctuations realizing the "Dot Sign". The individualization of this sign at an early age associated with splenomegaly allowed the diagnosis of a Caroli syndrome. While the diffuse medullary hyperechogenicity in the kidney allowed to evoke its association with polycystic kidney disease, especially the recessive one. Discussion and Conclusion: Caroli syndrome is a rare entity of autosomal recessive transmission. ..........

Rotatable sphincterotome as a rescue device for endoscopic retrograde cholangiopancreatography cannulation: a single-center experience.

Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism.

The trematode Fasciola hepatica is the most widespread causative agent of fasciolosis, a parasitic disease that mainly affects humans and ruminants worldwide. During F. hepatica infection, newly excysted juveniles (FhNEJ) emerge in the duodenum of the mammalian host and migrate towards their definitive location, the intra-hepatic biliary ducts. Understanding how F. hepatica traverses the intestinal wall and migrates towards the liver is pivotal for the development of more successful strategies against fasciolosis. The central enzyme of the mammalian fibrinolytic system is plasmin, a serine protease whose functions are exploited by a number of parasite species owing to its broad spectrum of substrates, including components of tissue extracellular matrices. The aim of the present work is to understand whether FhNEJ co-opt the functions of their host fibrinolytic system as a mechanism to facilitate trans-intestinal migration. A tegument-enriched antigenic extract of FhNEJ (FhNEJ-Teg) was obtained in vitro, and its capability to bind the zymogen plasminogen (PLG) and enhance its conversion to the active protease, plasmin, were analyzed by a combination of enzyme-linked immunosorbent, chromogenic and immunofluorescence assays. Additionally, PLG-binding proteins in FhNEJ-Teg were identified by bidimensional electrophoresis coupled to mass spectrometry analysis, and the interactions were validated using FhNEJ recombinant proteins. Our results show that FhNEJ-Teg contains proteins that bind PLG and stimulate its activation to plasmin, which could facilitate the traversal of the intestinal wall by FhNEJ and contribute to the successful establishment of the parasite within its mammalian host. Altogether, our findings contribute to a better understanding of host-parasite relationships during early fasciolosis and may be exploited from a pharmacological and/or immunological perspective for the development of treatment and control strategies against this global disease.

Surgical Treatment of Caroli Disease Unilobar: 8 Cases and Review of Literature

Introduction: Caroli disease is rare congenital disorder characterized by segmental intrahepatic bile duct ectasia always communicating with the bile ducts. Methods: The aim of this study for 08 cases of Caroli disease is to assess the role of surgery in the treatment of Caroli disease unilubar, focusing on epidemiological, clinical, anatomopathological and surgical aspects. Results: The middle age was 52,24 years with (4H/4F), this disease was located on the left in 7 cases and on the right in one case. It was manifested by abdominal pain (100%), cholangitis (25%), jaundice (25%) and fever (12,5). It was complicated by intrahepatic lithiasis (75%), liver abscess (27,5%) and cholangiocarcinoma (25%). Hepatic cholestasis was found in 3 cases. Imaging evoked the diagnosis by showing cystic dilatation of the intrahepatic bile ducts communicating with the biliary tree. Hepatic resection was the treatment of choice for 7 patients with bilio-digestive anastomosis on Y in 2 patients and a lateral-lateral choledoco-duodenal bypass in 2 patients. Histology confirmed the diagnosis in all cases. Two patients died 1 month after the procedure. Only one patient was lost to follow-up and the evolution was favorable for the other patients with a mean follow-up of 6 years. Conclusions: It seems evident that premature treatment followed by regular supervision makes it possible to detect and treat complications.

Low-phospholipid associated cholelithiasis (LPAC) syndrome: an unusual form in an elderly and overweight woman

BackgroundLow-phospholipid associated cholelithiasis (LPAC) remains an under-diagnosed condition. It can be revealed by complications such as acute cholecystitis, acute angiocholitis and acute pancreatitis. We report a case of acute pancreatitis secondary to LPAC syndrome.Case presentationA 58-year-old woman was hospitalized for recurrent biliary-type abdominal pain after cholecystectomies. The diagnosis of acute biliary pancreatitis revealing a low-phospholipid associated cholelithiasis syndrome was retained after explorations. An abdominal ultrasound performed by an expert radiologist allowed us to confirm the diagnosis of LPAC syndrome, showing a comet tail image along the intrahepatic bile ducts. Ursodeoxycholic acid was started without waiting for the result of the ABCB4 mutation. The outcome was spectacular with complete disappearance of the symptoms after the first week.ConclusionExpert ultrasound remains the key examination for the confirmation of the diagnosis of a low-phospholipid associated cholelithiasis syndrome. It should be requested at the slightest warning signs such as a young age less than 40 years and recurrence of biliary symptoms after cholecystectomy.

Association between sleep traits and primary liver cancer: A Mendelian randomization analysis.

Primary liver cancer (PLC) is the sixth most frequently occurring cancer, representing one of the top 5 leading causes of cancer-related mortality worldwide. Recently, researchers have focused more on the impact of living habits on the incidence and development of tumours. This study reports a relationship between sleep traits and PLC. In this study, we used published genome-wide association studies to obtain exposure factors of 6 sleep traits. Mendelian randomization (MR) analysis was used to assess the causal relationship between sleep traits and PLC via inverse-variance weighted (IVW), MR Egger and weighted median. Sensitivity analysis was used to reduce the bias. Our investigation revealed that there was a negative correlation between sleep duration and the group of liver and bile duct cancer by IVW (p-value = .042), and this result was similarly observed in the liver cell carcinoma group by Weighted Median (p-value = .026). In contrast, there was a positive correlation found between napping during the day and primary liver cancer in the cohorts of liver and bile duct cancer (p-value = .030), liver cell carcinoma (p-value = .043) and malignant neoplasm of other and unspecified parts of the biliary tract (p-value = .016) by IVW. Furthermore, our study also revealed a positive correlation between insomnia and malignant neoplasm of the liver and intrahepatic bile ducts by IVW (p-value = .022). Overall, our study indicates that insomnia and nap during the day may be risk factors of PLC and adequate night sleep might keep us away from PLC.

Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial

Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7-30·4). Median overall survival was 12·7 months (95% CI 11·5-13·6) in the pembrolizumab group versus 10·9 months (9·9-11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72-0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

A CASE OF INTRAOPERATIVE DISCOVERY OF ABERENT SUBVESICAL BILE DUCT DURING LAPAROSCOPIC CHOLECYSTECTOMY

Introduction. Subvesical bile ducts (Lyushka ducts) are tubular aberrant anatomical anomalies of the biliary tree, in which the intrahepatic bile ducts drain into the lumen of the gallbladder at different levels.
 According to various sources, this variant of the anatomical architecture of the bile ducts occurs in 1.7 - 3% of clinical cases.
 The relevance of knowing the anatomical features of the biliary tree is due to the fact that routine preoperative methods of examination in most cases do not allow to verify them, and unnoticed damage to such courses at the stage of extraction of the bile duct can lead to intraoperative and postoperative complications.
 Therefore, knowledge of the presence of such anatomical options is a condition for safe laparoscopic cholecystectomy (LC).
 Goal. To represent a clinical case of aberrant subvesical bile duct during LC.
 Presentation of a clinical case. The 41-year-old patient was hospitalized for acute biliary pancreatitis of mild severity according to the Ranson scale against the background of gallstone disease. In cooperation with related specialists, the patient underwent complex conservative treatment according to the updated recommendations for the management of acute pancreatitis (AP). After the normalization of basic laboratory indicators, exclusion of local parapancreatic complications, the patient was prepared for LC. Intraoperatively, a subvesical aberrant bile duct with a diameter of 1 mm was found, connecting the lumen of the gallbladder with the intrahepatic ducts of the IV segment of the liver. Coagulation of the bilious source was performed. A diagnostic tubular drainage was installed. No complications were observed in the early and late postoperative period.
 Discussion. Subvesical bile ducts, or "Lyushka's ducts" - anatomical variants of biliary tracts that flow directly into the gallbladder, perforating its wall at different levels.
 The etiology of Lyushka's movements is a subject of debate. The first theory describes them as an embryological abnormality of development in the early stages of embryogenesis. In our clinical case, it is quite likely that subvesical bile ducts could have arisen according to the second theory - hypertrophy of parenchymal branches as a result of previous local inflammation against the background of chronic cholecystitis and periodic exacerbation of cryptogenic hepatitis.
 Due to their small size, these movements can go unnoticed, causing various postoperative complications. Therefore, such ducts are of great clinical importance for surgeons. Their preoperative identification is often impossible, so they can be damaged intraoperatively.
 Bile leakage due to damage to aberrant ducts usually manifests itself clinically within the first postoperative week. In severe cases, the development of biliary peritonitis with subsequent sepsis is possible.
 In our case, cholelithiasis from the subvesical course was eliminated by coagulation. In cases of postoperative complications, according to the literature, endoscopic methods are the main method of treatment. A repeat laparotomy is very rarely necessary.
 Conclusions. Aberrant subvesical bile ducts are extremely rare and may be overlooked during hepatobiliary operations. Their damage occurs at the stage of separation of the ZHM from its bed and is therefore inevitable. Knowledge of their existence, intraoperative vigilance and delicate surgical technique allow to identify and timely prevent the development of complications.

ASO silencing of a glycosyltransferase, Poglut1 , improves the liver phenotypes in mouse models of Alagille syndrome.

Paucity of intrahepatic bile ducts (BDs) is caused by various etiologies and often leads to cholestatic liver disease. For example, in patients with Alagille syndrome (ALGS), which is a genetic disease primarily caused by mutations in jagged 1 ( JAG1) , BD paucity often results in severe cholestasis and liver damage. However, no mechanism-based therapy exists to restore the biliary system in ALGS or other diseases associated with BD paucity. Based on previous genetic observations, we investigated whether postnatal knockdown of the glycosyltransferase gene protein O -glucosyltransferase 1 ( Poglut1) can improve the ALGS liver phenotypes in several mouse models generated by removing one copy of Jag1 in the germline with or without reducing the gene dosage of sex-determining region Y-box 9 in the liver. Using an ASO established in this study, we show that reducing Poglut1 levels in postnatal livers of ALGS mouse models with moderate to profound biliary abnormalities can significantly improve BD development and biliary tree formation. Importantly, ASO injections prevent liver damage in these models without adverse effects. Furthermore, ASO-mediated Poglut1 knockdown improves biliary tree formation in a different mouse model with no Jag1 mutations. Cell-based signaling assays indicate that reducing POGLUT1 levels or mutating POGLUT1 modification sites on JAG1 increases JAG1 protein level and JAG1-mediated signaling, suggesting a likely mechanism for the observed in vivo rescue. Our preclinical studies establish ASO-mediated POGLUT1 knockdown as a potential therapeutic strategy for ALGS liver disease and possibly other diseases associated with BD paucity.

Gallstone ileus at 17 years after living donor liver transplantation: A case report

Gallstone ileus (GI) occurs in <0.1% of all cases of mechanical bowel obstruction. There have been a few reports of GI occurring after Kasai procedures or Roux-en-Y anastomosis for bariatric surgery. We herein report a case of GI that occurred over 17 years after liver transplantation (LT). A 33-year-old woman who had undergone living donor LT for biliary atresia at 16 years old and had been regularly followed on an outpatient basis in our hospital presented with the sudden onset of increased abdominal distension, pain, and nausea. Enhanced abdominal computed tomography showed dilatation of the intrahepatic bile duct and the whole intestinal tract of the Roux limb as well as ischemic changes near the jejuno-jejunal anastomosis. On laparotomy, a movable and hard foreign body was palpated in the intestinal tract close to the jejuno-jejunal anastomosis site. Enterotomy was performed, and a 4-cm gallstone was removed. The patient had a good postoperative course and was discharged on postoperative day 12. Although GI after LT is a rare complication, it may need to be differentiated as a cause of ileus. An accurate differential diagnosis and early reliable intervention for stone removal will help prevent serious bowel complication, which may lead to graft dysfunction.

SPECTRUM OF INTRAHEPATIC AND EXTRAHEPATIC BILIARY TREE VARIATIONS BY MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY IN A TERTIARY CARE HOSPITAL OF NORTH EAST INDIA

Background: Biliary tree anatomy shows many variations. MRCP is a non–invasive and fast method for direct visualisation of the intra and extrahepatic biliary ducts and the pancreatic duct. Therefore, MRCP is increasingly used for preoperative planning since anatomic variants of biliary tree may increase the complexity of surgical procedures and biliary interventions. The purpose of the study is to know the prevalence of variations in our population and to provide a preoperative knowledge for planning of surgical interventions. MRCP was Materials and Methods: conducted on 100 adult patient and were evaluated retrospectively. All the patients underwent MRCP with a 1.5 Tesla MR machine (GE MR Signa) with 8- channel phased array coils. In 100 adult patients 68 were female and 32 w Results: ere male. Out of 100 patients Huang Type A1 were found in 68 patients [68%], type A2 in 12 patients [12%], type A3 in 9 patients [9%], type A4 in 4 patients [4%] and type A5 in 1 patient. 6 patients [6%] show other type of variations. Intrahepatic and extrahepatic bile duct anatomy is Conclusion: complex with many common and uncommon variations. Preoperative biliary mapping by MRCP is needed to plan the surgery and helpful in reducing biliary complications, postoperative morbidity and mortality

Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells

AbstractBackgroundPrimary biliary cholangitis (PBC), an autoimmune liver disease, presents with progressive damage to the intrahepatic bile ducts with infiltrating mononuclear cells and the appearance of anti‐mitochondrial antibodies (AMAs). The initiation of autoimmune liver disease is permissively mediated by dysfunctional regulatory T cells (Treg cells). Naïve CD4+ T cells cultured with splenic B220+ cells without additional cytokines or chemicals can differentiate into specific types of Treg cells (Treg/B cells) without expressing forkhead box P3. In this study, we explored the effects of Treg/B cells on disease severity and changes in intestinal microbiota in a murine model of PBC.MethodsTreg/B cells were administered to 2‐octenoic acid‐induced PBC mice. Enzyme‐linked immunosorbent assay, flow cytometry and histopathological techniques were used to evaluate the severity of PBC and to assess its therapeutic effect. Diversity of the intestinal microbiota was determined using 16S rRNA sequencing. The suppressive mechanisms of Treg/B cells were investigated using the bone marrow‐derived dendritic cells (BMDCs).ResultsTreg/B‐cell treatment significantly decreased the levels of serum AMAs against pyruvate dehydrogenase complex E2, lowered the levels of serum bile acids, attenuated inflammatory cell infiltration, reduced dendritic cell activation, altered the population of T cells in the liver and alleviated liver collagen synthesis in PBC mice. In addition, the Treg/B‐cell treatment changed the faecal microbial diversity in PBC mice. Furthermore, Treg/B‐cell treatment decreased the levels of proinflammatory cytokines and expression of costimulatory molecules in BMDCs. This inhibitory effect was partially mediated by the cytotoxic T‐lymphocyte‐associated antigen 4 pathway.ConclusionTreatment with Treg/B cells in a murine model of PBC attenuated liver inflammation and altered the gut microbiota. Immune regulation of Treg/B cells may be a potential therapeutic strategy for treating autoimmune liver disease.

Assessment of a novel biliary-specific near-infrared fluorescent dye (BL-760) for intraoperative detection of bile ducts and biliary leaks during hepatectomy in a preclinical swine model.

Postoperative bile leakage is a common complication of hepatobiliary surgery and frequently requires procedural intervention. Bile-label 760 (BL-760), a novel near-infrared dye, has emerged as a promising tool for identifying biliary structures and leakage, owing to its rapid excretion and strong bile specificity. This study aimed to assess the intraoperative detection of biliary leakage using intravenously administered BL-760 compared with intravenous (IV) and intraductal (ID) indocyanine green (ICG). Laparotomy and segmental hepatectomy with vascular control were performed on two 25-30 kg pigs. ID ICG, IV ICG, and IV BL-760 were administered separately, followed by an examination of the liver parenchyma, cut liver edge, and extrahepatic bile ducts for areas of leakage. The duration of intra- and extrahepatic fluorescence detection was assessed, and the target-to-background (TBR) of the bile ducts to the liver parenchyma was quantitatively measured. In Animal 1, after intraoperative BL-760 injection, three areas of leaking bile were identified within 5 min on the cut liver edge with a TBR of 2.5-3.8 that was not apparent to the naked eye. In contrast, after IV ICG administration, the background parenchymal signal and bleeding obscured the areas of bile leakage. A second dose of BL-760 demonstrated the utility of repeated injections, confirming two of the three previously visualized areas of bile leakage and revealing one previously unseen leak. In Animal 2, neither ID ICG nor IV BL-760 injections showed obvious areas of bile leakage. However, fluorescence signals were observed within the superficial intrahepatic bile ducts after both injections. BL-760 enables the rapid intraoperative visualization of small biliary structures and leaks, with the benefits of fast excretion, repeatable intravenous administration, and high-fluorescence TBR in the liver parenchyma. Potential applications include the identification of bile flow in the portal plate, biliary leak or duct injury, and postoperative monitoring of drain output. A thorough assessment of the intraoperative biliary anatomy could limit the need for postoperative drain placement, a possible contributor to severe complications and postoperative bile leak.

Spontaneous biloma manifesting with massive upper gastrointestinal bleed: case report

Spontaneous biloma is a rare non-traumatic lesion in whi­ch the extrahepatic or intrahepatic bile duct perforates spontaneously with no discernable cause. We present a case of spontaneous biloma in a 68 years old male patient with cholelithiasis and concurrent choledocholithiasis, who presented with acute severe cholangitis. There was no history of abdominal surgery, instrumentation, or trauma in the past. Initial ultrasonography (USG) abdomen showed central intrahepatic dilation, cholelithiasis, and choledocholithiasis. A sizeable hypoechoic lesion with few internal septations was present adjacent to the left lobe of the liver, with USG suspicion of a hydatid cyst. The lesion was abutting and displacing the stomach anteromedially. The patient had an acute renal failure with hemodynamic instability at presentation. The patient was managed with emergency endoscopic drainage under ultrasound guidance and improved after that. On the fourth day, after endoscopic drainage, the patient had a massive upper gastrointestinal (UGI) bleed due to erosion and pressure necrosis of the gastric wall due to biloma. The patient was managed successfully with sleeve gastrectomy and de-roofing of the cyst.