Intrahepatic Ducts Research Articles

Abstract A025: Trends in liver cancer mortality by sex, race, and ethnicity in California from 2000-2019

Abstract Background: Liver cancer disproportionately affects foreign-born individuals and racial and ethnic minoritized groups, with higher incidence among Asian American/Pacific Islander (AAPI) and Hispanic populations than non-Hispanic (NH) White populations. California has one of the highest overall mortality rates from liver cancer and a large proportion of AAPI and Hispanic residents compared to other U.S states. While prior studies have examined racial and ethnic disparities in liver cancer incidence and treatment, few studies have examined trends in liver cancer mortality in California by sex, race, and ethnicity. Methods: Adults aged 20+ years diagnosed with first primary malignant liver and intrahepatic bile duct cancer from January 2000 through December 2019 were identified through the California Cancer Registry, a statewide population-based cancer registry. We used SEER*Stat software to compute age-adjusted mortality rates (per 100,000 population; standardized to the 2000 U.S. standard million population) by sex, race, and ethnicity. To analyze temporal trends of mortality rates, we calculated annual percent change (APC) using Joinpoint regression. Results: Overall, the mortality rate of liver cancer increased from 8.05 to 10.75 per 100,000 (average APC=1.53, 95% CI 1.23, 1.82) from 2000-2019. For males, rates increased from 11.39 in 2000 to 15.77 until 2013 (APC=2.53, 95% CI 2.07, 3.21), and stabilizing thereafter (APC=-0.74, 95% CI -2.37, 0.30). In contrast, for females, mortality rates increased continuously from 2000-2019 from 5.27 to 7.17 (APC=1.63, 95% CI 1.27, 2.04). Across racial and ethnic groups, the mortality rate for liver cancer was highest for the AAPI adults at 16.77 in 2000, and this decreased over time to 12.29 in 2019 (APC=-3.17, 95% CI -5.36, -2.24). Similarly, the liver cancer mortality rate among Hispanic adults increased initially and then decreased. Mortality among non-Hispanic Black adults increased from 10.98 in 2000 to 12.99 in 2019 (APC=0.89, 95% CI -0.07, 2.02), though this did not reach statistical significance. The liver cancer mortality rate was lowest among non-Hispanic White adults from 5.65 in 2000 but increased over time to 7.87 in 2019 (APC=1.76, 95% CI 1.39, 2.08), which is still the lowest compared to other racial and ethnic groups. Discussion: In contrast to studies that show a decline in liver cancer mortality in recent years, liver cancer mortality rates have continued to increase in California, particularly for females. Liver cancer mortality rates initially increased for AAPI and Hispanic populations but have started to stabilize. Next steps are to understand multilevel drivers contributing to these trends in liver cancer mortality in California, including individual sociodemographic and clinical factors, healthcare system factors, and neighborhood factors, including neighborhood socioeconomic status and ethnic enclaves. Citation Format: Janet N. Chu, Meera Sangaramoorthy, Meg Mckinley, Stephen Li, Mindy C. DeRouen, Alice Guan, Michele M. Tana, Ma Somsouk, Caroline A. Thompson, Chanda Ho, Hashem B. El-Serag, Iona Cheng, Scarlett L. Gomez, Salma Shariff-Marco. Trends in liver cancer mortality by sex, race, and ethnicity in California from 2000-2019 [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A025.

Analysis of the etiology and clinical indicators of infantile cholestasis

Objective: To explore the disease spectrum and corresponding clinical indicators of infantile cholestasis so as to provide a basis for the diagnosis of this type of disease at an early stage. Methods: The clinical data was collected from 203 hospitalized children diagnosed with infantile cholestasis at the Department of Gastroenterology of Maternal and Child Health Care, Guiyang City, from January 2018 to March 2023, including 130 males and 73 females. Patients general condition, personal history, and blood biochemical test indicators, including liver and coagulation function, blood ammonia, blood lipid profile, blood sugar, TORCH, thyroid function, and others, were retrospectively analyzed after admission. Cholangiography and high-throughput gene sequencing were performed in certain patients. The etiology of the enrolled cases were analyzed. Children's clinical data were compared with distinct inherited metabolic liver diseases (Group A) and biliary atresia (Group B). The statistical analysis was conducted using the t-test, Mann-Whitney test, Kruskal-Wallis test, or χ2 test, according to different data. Results: In 33 cases, infectious factors-primarily CMV infection-were the etiology of cholestasis. Forty cases had aberrant bile duct development, primarily biliary atresia, choledochal cysts, and intrahepatic bile duct dysplasia. In 26 cases, genetic metabolic factors mainly included citrin protein deficiency, sodium-taurocholate co-transporting polypeptide deficiency, and Alagille syndrome. 11 cases had drug/poisoning factors (parenteral nutrition-associated cholestasis). 19 cases had idiopathic infantile cholestasis. Three cases had other factors; however, all of them had Kawasaki disease. 71 cases had an unclear diagnosis. There was no statistically significant difference in terms of gender and age between groups A and B (P>0.05). The alkaline phosphatase (ALP) and bile acid levels were significantly higher in Group A than Group B, with a P<0.05, while the gamma glutamyltransferase (GGT), direct bilirubin (DBil), and albumin levels were lower than those in Group B, with a P<0.05. The cytomegalovirus infection rate was higher in Group B (62.50%) than Group A (34.62%), and the difference between the two groups was statistically significant (χ2=3.89, P<0.05). The alanine aminotransferase, aspartate aminotransferase, GGT, DBil, and albumin were significantly lower in patients with citrin protein deficiency than those in patients with biliary atresia, while ALP, bile acid, and blood ammonia were higher than those in patients with biliary atresia. Patients with sodium-taurocholate co-transporting polypeptide deficiency had higher bile acid than patients with biliary atresia, while the DBil was lower than that in patients with biliary atresia, and the difference was statistically significant (P<0.05). Conclusion: Infantile cholestasis etiology is diverse. ALP, bile acids, GGT, DBil, and albumin levels can serve as simple indicators for early-stage differentiation between inherited metabolic liver disease and biliary atresia. The cholestasis etiology should be determined as early as possible following biliary atresia exclusion by actively completing genetic metabolic gene detection.

Trends in Cancer Incidence and Mortality in US Adolescents and Young Adults, 2016-2021.

(1) Background: The incidence rate of early onset-cancer (<50) has increased since 1995. Among younger people, cancers in AYAs (aged 15-39 y) are often biologically distinct tumors from those treated in the pediatric and older adult population. The current study describes trends in the United States for the most recent years including the first year of the COVID-19 epidemic. We aimed to describe the recent incidence and mortality trends of cancers in AYAs (aged 15-39 y). (2) Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER 22) from 1 January 2016 to 31 December 2021. Age-adjusted incidence and mortality rates were assessed by SEER*Stat 8.4.3 for major cancer types by sex, race/ethnicity, age, and metropolitan/nonmetropolitan status. Time trends of age-adjusted incidence and mortality rates were examined by sex and metropolitan/nonmetropolitan status. (3) Results: Age-adjusted overall cancer incidence and mortality rates were stable during this study period. The age-adjusted incidence rates declined significantly for ependymoma, melanoma, carcinomas of lung, bronchus, and trachea, unspecified malignant neoplasms, and non-Hodgkin's lymphoma. Significant increases were found for gastrointestinal tract cancers and non-Kaposi sarcomas. The age-adjusted mortality rate decreased for acute myeloid leukemia, melanoma, carcinomas of liver and intrahepatic bile ducts, kidney and, in women, leukemia. For some cancers, rates differed by sex, race, ethnicity, and geography. Monitoring the rates and time trends of AYA cancer emphasizes the distinct health concern for this age group.

A case series of prenatal hepatic hilar cyst in the presence of a gallbladder - navigating the dilemma between biliary atresia and choledochal cyst

BackgroundPrenatally diagnosed hepatic hilar cysts are a challenging finding for the clinician. They can either be a sign of cystic biliary atresia (BA) or a choledochal cyst (CC), two diagnoses with different postnatal management and prognosis. Based on a case report of four patients, we aim to propose a management algorithm for prenatally diagnosed “hepatic hilar cysts”.Case presentationA hepatic hilar cyst, ranging from 5 to 25 mm, was detected prenatally in all four girls confirmed postnatally along with the presence of a gallbladder. Stool color was normal until two weeks of life at which time the stool color became lighter, and the patients developed cholestasis. All were operated before seven weeks of life: Case 1 had a CC with patent but irregular intrahepatic bile ducts at intraoperative cholangiogram, and no communication with the duodenum. A Roux-en-Y bilioenteric anastomosis was performed. The cyst showed complete epithelial lining loss, and liver pathology showed BA features. Case 2 had the final diagnosis of cystic BA with patent but abnormal intrahepatic bile ducts. She underwent two operations: the first operation at four weeks as described for case 1, since intraoperative findings were similar, as was histology. As cholestasis increased postoperatively, she underwent a Kasai hepato-porto-enterostomy six weeks later, where distinct BA findings were found with complete scarring of the hilar plate. Case 3 had a cystic BA with the cyst located within the common bile duct and atretic bile ducts proximal to the porta hepatis. It exhibited no communication with the liver or duodenum. A Kasai operation was performed, with histology showing complete epithelial loss within the cyst wall and scarring of the hilar plate. Case 4 had a cystic BA presenting a completely obliterated hepatic duct with the cyst lying within the common bile duct. A Kasai procedure was performed. Histology showed a common bile duct with a residual lumen of 0.1 mm.ConclusionsThe spectrum of disease from CC to BA in the setting of a prenatally discovered hepatic hilar cyst is emphasized. Even if cholangiogram differentiates most patients with BA from those with CC, caution is advised for transitional types.

The dynamics of mortality from malignant neoplasms of the liver and intrahepatic bile ducts in the Sverdlovsk region over a fifteen-year period.

The dynamics of mortality from malignant neoplasms of the liver and intrahepatic bile ducts in the Sverdlovsk region over a fifteen-year period.

Clinical application of prone position to suppress respiratory movement artifacts in supine position during magnetic resonance cholangiopancreatography/MRI.

To compare the image quality of magnetic resonance cholangiopancreatography (MRCP) in the supine position and prone position under the conditions of the same equipment, the same sequence (3D Navigator Triggered Sampling Perfection with Application-Optimized Contrast Using Different Flip-angle Evolutions, 3D-NT-SPACE) and the same patient, and to explore the clinical application value of prone position in MRCP examination to suppress respiratory motion artifacts. 53 participants who underwent MRCP in our hospital from April 2020 to August 2022 were prospectively collected. The 3D-NT-SPACE sequence was used in these patients. The visibility of the common bile duct, common hepatic duct, main pancreatic duct, and first- and second- and third-level branches of the intrahepatic bile duct and the comfort of the participants in two positions were subjective-evaluated. The Signal-to-noise ratio (SNR) and contrast-to-noise ratio were objective-evaluated. Statistical analysis was performed using Shapiro-Wilk, Levene's, Mann Whitney U test, Pearson chi-square test, and one-sample chi-square test. 53 patients (51.92years ± 2.02, 20 men) were evaluated. There were significant differences in the second- and third-level branches visibility score, the main pancreatic duct visibility score, the image quality score of the pancreaticobiliary tree, the blur and motion artifact score, the total image quality score, and SNR between the two positions (p < 0.05). The overall image quality of the prone position was better than that of the supine position. The prone position is a useful complement to the supine position.

EP72 - Spontaneous Hepatic subcapsular Biloma Secondary to Choledocholithiasis with concurrent calculous cholecystitis

Abstract Introduction The term "Biloma," introduced in 1979 by Gould and Patel, denotes an encapsulated extrahepatic bile collection primarily caused by iatrogenic or traumatic injuries1. Spontaneous Biloma, a rare non-traumatic occurrence, involves the spontaneous perforation of extrahepatic or intrahepatic bile ducts. In our case report, the spontaneous Biloma developed because of an abrupt increase in bile duct pressure secondary to biliary obstruction because of choledocholithiasis 2. Case Report We present an 85-year-old male with calculous cholecystitis and concurrent choledocholithiasis, leading to acute severe cholangitis. There was no history of surgery, instrumentation, or trauma. He exhibited hemodynamic instability and acute renal failure. Diagnostic tests revealed raised inflammatory markers and deranged liver and kidney functions. CT scans unveiled a large subcapsular liver collection compressing the parenchyma (Figure a &amp;b), alongside dilated intrahepatic biliary radicles, common bile duct, and choledocholithiasis. Treatment Nowadays, treatment for spontaneous Biloma is nonsurgical. Urgent endoscopic drainage and percutaneous transhepatic cholangiogram (PTC) – (Figure c) were performed, followed by ERCP, sphincterotomy, and stone removal (Figure d) once the patient stabilized3. Subsequent CT scans indicated resolution of the subcapsular collection (Figure e). During recovery, the patient experienced a small pulmonary embolism, managed conservatively. Conclusion This case underscores the rare occurrence of spontaneous hepatic subcapsular Biloma associated with choledocholithiasis in an elderly patient. Timely intervention with endoscopic and radiological procedures proved effective, leading to resolution of the Biloma and successful management of causative pathology.

Central role for cholangiocyte pathobiology in cholestatic liver diseases.

Cholangiopathies comprise a spectrum of chronic intra- and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis and often cirrhosis and its sequela. Treatment for these diseases is limited and collectively they are one of the therapeutic "black boxes" in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators, but also common cellular and molecular events driving disease progression (e.g., cholestatic fibrogenesis, inflammation, and duct damage). The common pathways involve cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, which are central to the pathogenesis of these disorders. Current information suggests that cholangiocytes function as a signaling "hub" in biliary tract-associated injury. Herein, we review the pivotal role of cholangiocytes in cholestatic fibrogenesis, focusing on crosstalk between cholangiocytes and portal fibroblasts and hepatic stellate cells. The proclivity of these cells to undergo a senescence-associated secretory phenotype which is pro-inflammatory and -fibrogenic, and the intrinsic intracellular activation pathways resulting in secretion of cytokines and chemokines is reviewed. The crosstalk between cholangiocytes and cells of the innate (neutrophils and macrophages), and adaptive (T-cells and B-cells) immune systems is also examined in detail. The information will help consolidate information on this topic, guide further research and potential therapeutic strategies for these diseases.

Rhabdomyosarcoma of the Biliary Tract in Children: Analysis of Single Center Experience.

Rhabdomyosarcoma (RMS) of the biliary tract is a rare tumor in children, constituting 0.5-0.8% of all pediatric RMS. Still, it is the most common malignancy in this location in children. Due to its rarity and location, it may cause diagnostic and treatment difficulties. Above all, there are no therapeutic guidelines specific for this tumor location. The aim of the study was to present an analysis of our experience with the treatment of children with biliary tract rhabdomyosarcoma (RMS) and discuss clinical recommendations for this specific location published in the literature. A retrospective analysis of medical records of eight children with biliary tree RMS treated in one center between 1996-2022 was performed. Records of eight children, five boys and three girls aged 2 yrs 6 mo to 16 yrs 9 mo (median-6 yrs) were analyzed. All patients presented with jaundice as the first symptom. In two patients, initial diagnosis of a tumor was established. For the remaining six, the primary diagnoses were as follows: choledochal cyst-one, malformation of the biliary ducts-one, choledocholithiasis-one, cholangitis-three. In four patients, the extrahepatic bile ducts were involved; in four patients, both the intrahepatic and extrahepatic bile ducts were involved. Embryonal RMS was diagnosed in seven patients (three botryoides type). Alveolar RMS was found in one patient. Biopsy (three surgical, four during endoscopic retrograde cholangiopancreatography (ERCP)) was performed in seven patients. One child underwent primary partial tumor resection (R2). Seven patients received neoadjuvant chemotherapy, followed by delayed resection in five, including liver transplantation in one (five were R0). Two patients did not undergo surgery. Radiotherapy was administered in four patients (two in first-line treatment, two at relapse/progression). Six patients (75%) are alive with no evidence of disease, with follow-up ranging from 1.2 yrs to 27 yrs (median 11 yrs. and 4 mo.). Two patients died from disease, 2 y 9 mo and 3 y 7 mo from diagnosis. Children presenting with obstructive jaundice should be evaluated for biliary tract RMS. The treatment strategy should include biopsy and preoperative chemotherapy, followed by tumor resection and radiotherapy for residual disease and in case of relapse.

Unveiling the unexplored secret: Aggressive behavior and poor survival in intrahepatic mucinous adenocarcinoma compared to conventional adenocarcinoma.

Intrahepatic bile duct mucinous adenocarcinoma (IHBDMAC) is a rare pathological subtype of intrahepatic cholangiocarcinoma (IHCC), and its tumor biological features and survival outcomes have rarely been explored, especially when compared to the most common subtype, intrahepatic bile duct adenocarcinoma (IHBDAC). Therefore, the aim of this study was to explore the clinical features and survival outcomes of IHBDAC and IHBDMAC using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. A total of 1,126 patients were included, with 1,083 diagnosed with IHBDAC and 43 diagnosed with IHBDMAC. Patients with IHBDMAC presented with a more advanced T stage (55.8% vs. 36.9%, P = 0.012) and higher rate of lymph node metastasis (37.2% vs. 24.9%, P = 0.070). Cox regression identified advanced T stage, lymph node metastasis, and distant metastasis as poor survival predictors, while chemotherapy and surgery were protective factors. Survival analyses revealed significantly worse overall survival (OS) and cancer-specific survival (CSS) for IHBDMAC compared to IHBDAC (P < 0.05). Even after matching, patients with IHBDMAC still had a worse prognosis than those with IHBDAC. These findings highlight the aggressive nature of IHBDMAC and the need for tailored therapeutic strategies. Future research should focus on prospective studies and molecular insights to develop targeted treatments for IHBDMAC.

The significance of neuroendocrine component in cases with intrahepatic cholangiocarcinoma: A SEER-based retrospective cohort study

ObjectiveTo evaluate the significance of neuroendocrine component in cases with intrahepatic cholangiocarcinoma (IHCC). MethodsCases with IHNECA and IHBDAC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively reviewed and analyzed. Comparative analyses in terms of clinic-pathological features and long-term survival were performed between cases with intrahepatic neuroendocrine carcinoma (IHNECA) and intrahepatic bile duct adenocarcinoma (IHBDAC). ResultsA total of 5211 cases with IHCC were included (103 with IHNECA and 5108 with IHBDAC). Comparable age status (P=0.168), sex status (P=0.274), and cirrhosis status (P=0.480) were acquired between two groups while inconsistent distributions in races (P=0.027) and marital status (P=0.028) were also acquired. Cases with IHBDAC were generally in a more advanced stage and shared a worse prognosis. A significantly higher incidence of lymph node metastasis was detected among cases with IHBDAC (24.8% vs 15.5%, P=0.031). Although the overall surgery rate was comparable between two groups (P=0.519), chemotherapy (53.0% vs 37.9%, P=0.002) and radiotherapy (6.0% vs 1.0%, P=0.032) were more frequently performed with a much higher cancer-related death (CRD) (79.4% vs 58.3%, P<0.001) acquired in cases with IHBDAC. INHECA served as an independent protective factor for cases with IHCC. Even after matching, cases with IHBDCA still shared a higher incidence with CRD (P=0.010) and a worse prognosis, especially for cases who received surgery. ConclusionIHNECA was associated with less aggressive tumor biological features and worse prognosis. More in-depth research focusing on IHNECA with more detailed clinical and pathological data is required.

Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel

In fetal development, tissue interaction such as the interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here we recapitulate the spatial arrangement between liver epithelial tissue and the portal vein to observe the formation of intrahepatic bile ducts (BDs) from human induced pluripotent stem cells (hiPSC). We co-culture hiPSC-liver progenitors on the artificial BV consisting of immature smooth muscle cells and endothelial cells, both derived from hiPSCs. After 3 weeks, liver progenitors within hiPSC-BV-incorporated liver organoids (BVLO) differentiate to cholangiocytes and acquire epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO temporarily attenuates cholestatic injury symptoms. Single cell RNA sequence analysis suggests that BD interact with the BV in BVLO through TGFβ and Notch pathways. Knocking out JAG1 in hiPSC-BV significantly attenuates bile duct formation, highlighting BVLO potential as a model for Alagille syndrome, a congenital biliary disease. Overall, we develop a novel 3D co-culture method that successfully establishes functional human BDs by emulating liver epithelial-BV interaction.

Fully-Covered Self-Expandable Metal Stent for Hepaticojejunostomy Anastomotic Stricture After Living Donor Liver Transplantation: A Case Series

We prospectively evaluated 3 cases regarding the usefulness of fully-covered self-expandable metal stents (FCSEMSs) for hepaticojejunostomy anastomotic stricture (HAS) after living donor liver transplantation (LDLT), which could not be resolved with conventional treatment using a plastic stent. All patients underwent LDLT with Roux-en-Y reconstruction; therefore, a short-type double-balloon enteroscope was used for the endoscopic procedures. HAS was observed on enteroscopic view of endoscopy in patients 1 and 2, and cholangiography revealed dilatation of the intrahepatic bile duct. The FCSEMS was successfully placed without the report of adverse events. The FCSEMS was removed after 16 weeks, and the HAS improved in both patients. In addition, stone clearance was also achieved in patient 2. On the other hand, FCSEMS was not placed in patient 3 because there was no indication of FCSEMS placement due to the multiple segmental biliary strictures (pruned-tree appearance on cholangiography). Subsequent deceased-donor liver transplantation confirmed recurrent primary sclerosing cholangitis. In this case, magnetic resonance cholangiopancreatography (MRCP) was not performed prior to cholangiography to rule out PSC recurrence. FCSEMS placement may be effective and safe for HAS after LDLT, which is not resolved with conventional treatment using a plastic stent. MRCP should be used to identify HAS prior to invasive cholangiography.

Diagnostic Accuracy of Ultrasound in Cholestatic Infants with Biliary Atresia.

Biliary atresia (BA) is an obstructive cholangiopathy that involves the intrahepatic and extrahepatic bile ducts. Ultrasound (US) can aid in evaluation of the biliary system and be efficiently used in daily practice. However, most studies on US for diagnosing BA have been conducted in developed countries. Therefore, we have aimed to evaluate the diagnostic accuracy of US in BA in infants with cholestasis from a developing country. This retrospective study used data collected from our hospital medical records. The US findings were compared with the gold standard intraoperative or cholangiography findings. Thirty-five BA patients (19 males and 16 females) and 36 controls (20 males and 16 females) were included in the study. Most of the patients (85.7%) were ≤ 6 months old. The absence of a gallbladder demonstrated 71.42% sensitivity (Sn), 91.67% specificity (Sp), 89.29% positive predictive value (PPV), 76.74% negative predictive value (NPV), 8.57 positive likelihood ratio (LR+), and 0.31 negative likelihood ratio (LR-) for diagnosing BA. The triangular cord sign demonstrated 14.28% Sn, 100% Sp, 100% PPV, 76.74% NPV, ∞ LR+, and 0.86 LR- for diagnosing BA. The combination of gallbladder absence and a positive triangular cord sign demonstrated 82.85% Sn, 91.67% Sp, 90.63% PPV, 84.61% NPV, 9.95 LR+, and 0.19 LR- for diagnosing BA. The diagnostic accuracy of US in BA is high, indicating that it can be the imaging tool of choice in infants with cholestasis. Ultrasound is safe and can be easily used in daily practice without the risk of radiation exposure.

Lymphotoxin beta-activated LTBR/NIK/RELB axis drives proliferation in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the intrahepatic (iCCA) or extrahepatic (eCCA) bile ducts with poor prognosis and limited treatment options. Prior evidence highlighted a significant contribution of the non-canonical NF-κB signalling pathway in initiation and aggressiveness of different tumour types. Lymphotoxin-β (LTβ) stimulates the NF-κB-inducing kinase (NIK), resulting in the activation of the transcription factor RelB. However, the functional contribution of the non-canonical NF-κB signalling pathway via the LTβ/NIK/RelB axis in CCA carcinogenesis and progression has not been established. Human CCA-derived cell lines and organoids were examined to determine the expression of NF-κB pathway components upon activation or inhibition. Proliferation and cell death were analysed using real-time impedance measurement and flow cytometry. Immunoblot, qRT-PCR, RNA sequencing and insitu hybridization were employed to analyse gene and protein expression. Four invivo models of iCCA were used to probe the activation and regulation of the non-canonical NF-κB pathway. Exposure to LTα1/β2 activates the LTβ/NIK/RelB axis and promotes proliferation in CCA. Inhibition of NIK with the small molecule inhibitor B022 efficiently suppresses RelB expression in patient-derived CCA organoids and nuclear co-translocation of RelB and p52 stimulated by LTα1/β2 in CCA cell lines. In murine CCA, RelB expression is significantly increased and LTβ is the predominant ligand of the non-canonical NF-κB signalling pathway. Our study confirms that the non-canonical NF-κB axis LTβ/NIK/RelB drives cholangiocarcinogenesis and represents a candidate therapeutic target.

COVID-19-Related Cholangiopathy: Histological Findings.

We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51-60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390-1256); GGT 925 (664-2169); ALT 100 (86-113); AST 87 (68-106); and bilirubin 4 (1-9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150-249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.

Rupture of intrahepatic bile duct after ERCP for common bile duct stone: A case report of rare complications.

Complications after endoscopic retrograde cholangiopancreatography (ERCP) are diverse and usually treated with nonoperative management or percutaneous drainage; however, there are still some rare, life-threatening complications. This is an extremely rare case of biliary peritonitis caused by rupture of the intrahepatic bile duct after ERCP. A 63-year-old male underwent ERCP for common bile duct stones. On the second day after the procedure, the patient developed sepsis and abdominal distention. Contrast-enhanced computed tomography revealed a subcapsular hepatic fluid collection attached to the bile duct of segment VII. Sepsis resulted in liver parenchyma rupture and intrahepatic bile duct injury after ERCP. Intraoperative cholangiography revealed a connection between a hole in the liver parenchymal surface and the intrahepatic bile duct. Surgeons performed the cholecystectomy, inserted a T-tube into the common bile duct stones, sutured the defect, and put 2 drainage tubes around the lesion. Postoperative recovery was uneventful, and the patient was discharged on the 17th postoperative day. Intrahepatic bile duct perforation after ERCP can lead to rupture of the liver parenchyma, biloma, or abdominal peritonitis. Multidisciplinary management is necessary to achieve favorable outcomes.

Efficiency of Anatomical Hepatectomy in the Treatment of Hepatic Cystic Echinococcosis.

Introduction: Total cystectomy and hepatectomy are the main radical surgical procedures for hepatic cystic echinococcosis (CE). When CE lesions severely invade intrahepatic biliary ducts and vessels or single or multiple lesions occupy one hepatic lobe, performing total cystectomy is not indicated. This study aimed to analyze the clinical efficiency of anatomical hepatectomy in the treatment of patients with hepatic CE. Methods: Clinical data of 74 patients with hepatic CE who received anatomical hepatectomy were retrospectively analyzed from January 2005 to January 2022. The patients were classified into the intrahepatic biliary duct invasion group (group A), the intrahepatic vessel invasion group (group B), and the hepatic lobe occupation group (group C). Results: Among these 74 patients who received anatomical hepatectomy, right hepatectomy was performed in 20 cases (27.03%), left hepatectomy in 26 cases (35.13%), right posterior lobectomy in nine cases (12.16%), and left lateral sectionectomy in 19 cases (25.68%). Short-term post-operative complications occurred in seven cases (9.50%), including abdominal abscess in one case, pleural effusion in three cases, intestinal obstruction in one case, incision infection in one case, and ascites in one case. Long-term post-operative complications occurred in four cases (5.4%), including recurrences of CE in two cases and incisional hernias in another two cases. There were no statistical differences in the concentrations of total bilirubin, alanine aminotransferase, and aspartic transaminase before and after surgery between groups (p > 0.05). However, differences in operative time, short-term post-operative complications, average hospital stay, and number of open hepatectomy cases were statistically significant between groups (p < 0.05). The differences in cases receiving hepatic portal occlusion, intra-operative blood loss, and intra-operative blood transfusion were not statistically significant between groups (p > 0.05). Conclusions: Anatomical hepatectomy is an effective and feasible surgical procedure for patients with hepatic CE with severe invasion of intrahepatic biliary ducts and vessels or patients with huge lesions occupying one hepatic lobe, which effectively avoids residual cavity-related complications.

Laparoscopic Right Hemi-hepatectomy of the Bile Duct-Obstructed Area Guided by Real-Time Fluorescence Imaging.

The regions of the liver with cholestasis caused by biliary tumors or thrombosis can be distinctly identified using indocyanine green (ICG) fluorescence imaging.1 The authors' team reported the application of bile-duct obstructed area imaging (BOAI) to assist open hepatectomy for intrahepatic cholangiocarcinoma (ICC) combined with intrahepatic bile duct obstruction previously.2 This video is the first report of real-time BOAI-guided three-dimensional (3D) laparoscopic hepatectomy using a 3D-4K fluorescence imaging system. A 65-year-old man was admitted to the authors' institution with clonorchiasis. Preoperative computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed an obstruction and diffuse dilation of the right hepatic duct. A 15-min retention of ICG (ICG R15) was performed 5 days before the operation, with a 3.3% result. Preoperative planning involved performing laparoscopic right hemi-hepatectomy with regional lymph node dissection assisted by visualization technology.3 During the procedure, significant fluorescence accumulation in the right liver was shown by fluorescence imaging. With the guidance of real-time BOAI (Fig. 1), the regions of biliary obstruction were precisely resected, and the middle hepatic vein (MHV) was passively and adequately exposed on the cutting plane. Fig. 1 Administration steps for real-time bile duct-obstructed area imaging. A ICG is injected intravenously 3-5 days before operation at a dose of 0.5 mg/kg. B ICG is accumulated in the whole liver within a few minutes after injection. C ICG is selectively absorbed by the liver and excreted into the intestines, whereby it is retained in areas of biliary obstruction RESULTS: The histopathologic diagnosis indicated high-grade intraepithelial neoplasia of the right bile duct tumor without lymph node metastases and clonorchiasis. The duration of the operation was 300 min, with an intraoperative blood loss of 50 ml. No postoperative complications occurred, and the patient was discharged after 7 days. Laparoscopic right hemi-hepatectomy for the bile-duct obstructed area with the guidance of real-time BOAI is feasible and effective.

Dental floss clip traction-assisted endoscopic ultrasound-guided hepaticogastrostomy for transluminal intrahepatic bile duct stone fragmentation and removal.

Dental floss clip traction-assisted endoscopic ultrasound-guided hepaticogastrostomy for transluminal intrahepatic bile duct stone fragmentation and removal.