Intrahepatic Ducts Research Articles

Perspective of tumor heterogeneity for treatments of intrahepatic cholangiocarcinoma with intrahepatic lithiasis

The heterogeneity of tumors results in significantly distinct biological characteristics of intrahepatic cholangiocarcinoma (ICC) caused by different etiologies. Among them, ICC caused by intrahepatic lithiasis (IHL-ICC) presents challenges in early detection, tumor staging, and surgical treatment, and has the poorest prognosis among all etiologies of ICC patients. Thus, it is essential to focus on early assessment of the possibility of developing ICC, prompt intervention of intrahepatic lithiasis, anatomical resection of hepatic parenchyma corresponding to the branch of the intrahepatic bile duct undergoing cancerous transformation, and enhanced postoperative follow-up of hepatolithiasis and ICC for IHL-ICC patients. These interventions are crucial to improve the clinical outcomes and overall survival of IHL-ICC patients.

The protective effect of forsythiaside A on 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestatic liver injury in mice: Based on targeted metabolomics and molecular biology technology

Cholestasis is a disorder of bile secretion and excretion caused by a variety of etiologies. At present, there is a lack of functional foods or drugs that can be used for intervention. Forsythiaside A (FTA) is a natural phytochemical component isolated from the medicinal plant Forsythia suspensa (Thunb.) Vahl, which has a significant hepatoprotective effect. In this study, we investigated whether FTA could alleviate liver injury induced by cholestasis. In vitro, FTA reversed the decrease in viability of human intrahepatic bile duct epithelial cells, the decrease in antioxidant enzymes (SOD1, CAT and GSH-Px), and cell apoptosis induced by lithocholic acid. In vivo, FTA protected mice from 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury, abnormal serum biochemical indexes, abnormal bile duct hyperplasia, and inflammatory infiltration. Furthermore, FTA treatment alleviated liver fibrosis by inhibiting collagen deposition and HSC activation. The metabonomic results showed that DDC-induced bile acid disorders in the liver and serum were reversed after FTA treatment, which may benefit from the activation of the FXR/BSEP axis. In addition, FTA treatment increased the levels of antioxidant enzymes in the serum and liver. Meanwhile, FTA treatment inhibited ROS and MDA levels and cleaved caspase 3 protein expression, thereby reducing DDC-induced hepatic oxidative stress and apoptosis. Further studies showed that the antioxidant effects of FTA were dependent on the activation of the BRG1/NRF2/HO-1 axis. In a word, FTA has a significant hepatoprotective effect on cholestatic liver injury, and can be further developed as a functional food or drug to prevent and treat cholestatic liver injury.

Clinical study on early predictors of concurrent bile duct injury following TACE in patients with liver cancer

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.

Cancer risks in a population-based study of agricultural workers: results from the Taiwan's Farmers and Health Cohort study.

The purpose of this study was to assess cancer risk among agricultural workers compared to the general population. The study utilized data from Farmers' Health Insurance (FHI) in Taiwan, which enrolled agricultural workers (N=1 175 149). The enrolled workers were matched to a general population (N=1 175 149) of the same age, gender, township, and enrollment year. The study population was linked to the National Cancer Registry to identify new cancer cases between 2000 and 2018. The Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval for outcomes. During the study period, 136 913 new cancers among agricultural workers were identified. The study found that male farmers had an increased cancer risk, including lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma (NHL), oral cancer, lip cancer, esophagus cancer, rectum and rectosigmoid junction cancer, liver and intrahepatic bile duct cancer, lung cancer, trachea and bronchi cancer, and other non-melanoma skin cancer, even when considering the latency period. Female farmers had an elevated risk of multiple myeloma and other non-melanoma skin cancer. Moreover, only lymphoma, NHL, other lymphoid, and multiple myeloma, were both found to occur at different insurance periods. This study provides farmer cancer patterns and risk, adding to the evidence that farmers are at increased risk of certain types of cancer, especially for hematological cancers. As exposure varies by farm operation type, individual farmer exposure may vary widely. Further understanding of the complex relationship between occupational exposure, environmental factors, and lifestyle factors is needed.

TAGNet: A transformer-based axial guided network for bile duct segmentation

Automatic segmentation of intrahepatic bile ducts and common bile ducts plays an essential role in interventional surgery for cholangiocarcinoma, directly related to the success rate of the operation. However, the large shape and appearance variances make it challenging to segment bile ducts, especially for 3D CT images. In this study, we propose a transformer-based axial guided network, dubbed TAGNet, to automatically segment intrahepatic and common bile ducts by exploiting intra- and inter-slice context modeling. The pivot is to take advantage of CNN-transformer hybrid architecture to simultaneously explore local and global contextual information from multiple adjacent slices. Especially a novel slice-axial-attention transformer module is imposed at multi-scales concurrently to capture the intra- and inter-slice feature representations along each direction, boosting long-distance contextual modeling while limiting the computation cost. Moreover, a slice-guided consistency loss function is advanced to enforce anatomical prior consistency among adjacent slices in a semi-supervised manner, thus enhancing the spatial topology of bile duct segmentation. Extensive experimental results on an in-house bile ducts CT dataset demonstrate that our method is capable of achieving promising performance, which achieves at least a 4.5% improvement in Dice and a reduction of 1.5 in HD95 than other state-of-the-art methods, indicating its potential for automated intrahepatic and common bile duct segmentation. We have made our code publicly available via https://github.com/zephyrize/TAGNet.

Successful endoscopic treatment of multiple large intrahepatic bile duct stones with benign choledochojejunal anastomotic stenosis.

Successful endoscopic treatment of multiple large intrahepatic bile duct stones with benign choledochojejunal anastomotic stenosis.

Incidence and Patterns of Digestive Organ Cancer in Georgia: Insights from a Population-Based Registry Study in 2021.

Digestive organ cancer, also known as gastrointestinal (GI) cancer, refers to cancer that occurs in the digestive tract. In this population-based registry study, we aimed to investigate the incidence of GI in Georgia and to identify any patterns in the occurrence of different types of this disease. The study included all cases of GI cancer that were diagnosed in Georgia in 2021. We analyzed 1635 patients' data to determine the overall and age-standardized incidence of GI cancer in the country. The analyses were performed for esophagus, stomach, colon, rectum, anus, liver and intrahepatic bile ducts, gallbladder, and pancreas separately. The descriptive statistics used in the study-specifically counts, means, proportions, and rates-were calculated using the statistical software STATA version 17.0. (StataCorp, College Station, TX, USA). The results of the study showed that the incidence of digestive organ cancer in Georgia was similar to the global average. However, there were some notable differences in the specific types of GI cancer that were most common in the country. Overall, this study provides important insights into the incidence of digestive organ cancer in Georgia and highlights the need for further research to better understand the factors that contribute to this disease.

Tea consumption and cancer: a Mendelian randomization study

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

Long-Term Feasibility of Rescue Reconstruction for Isolated Bile Ducts With Using Cystic Duct in Living Donor Liver Transplantation

The isolated bile duct is sometimes observed in the right liver graft of living donor liver transplantation (LDLT). Even though, as a rescue option, it is known to use the recipient's cystic duct (CyD) for duct-to-duct anastomosis, the long-term feasibility of rescue duct-to-CyD (D-CyD) anastomosis remains unclear. We prospectively collected data in the right liver-LDLT cohort and compared rescue D-CyD anastomosis (n=4) with standard duct-to-hepatic duct (D-HD, n=45) anastomosis (D-CyD group, n=4). The observation period was over 5 years (range, 68-171 mo) after LDLT. The D-CyD group included the following anastomosis procedures: anastomosis between the intrahepatic bile duct of the graft and the CyD of the recipient and anastomosis between the posterior HD and the CyD. Surgical outcomes between the 2 groups are similar, excluding the time for the biliary reconstruction (D-CyD, 116 ± 13 min vs D-HD, 57 ± 3 min). During the period, one recipient in the D-CyD group exhibited postoperative biliary stricture and biliary stone, and 6 recipients underwent those complications in the D-HD group (D-CyD, 25.0% vs D-HD, 13.3%) All recipients in the D-CyD group are presently alive and have not experienced liver dysfunction. Our findings suggest that rescue D-CyD anastomosis for an isolated bile duct in a right liver LDLT is acceptable as a life-saving option in terms of long-term feasibility.

Real-Time Fluorescent Cholangiography by Intrabiliary Indocyanine Green Administration With Near-Infrared Laparoscopy in Major Hepatectomy.

Biliary injury is a severe complication that can be associated with liver surgery. Intrahepatic biliary anatomy can be evaluated using magnetic resonance cholangiopancreatography and X-ray cholangiography; however, an intraoperative real-time bile duct visualization method has not yet been reported. This study aimed to demonstrate the availability of real-time fluorescent cholangiography (FC) by intrabiliary indocyanine green administration with near-infrared laparoscopy in major hepatectomy. The optimal concentration of indocyanine green (ICG) solution was examined ex vivo. The fluorescence intensity of the ICG solution and its mixture with bile was measured. Using a clinical trial model, ICG solution was injected into the cystic duct, followed by near-infrared laparoscopy performed during hepatectomy. The optimal concentration of ICG solution for FC was between 0.01 and 0.05 mg/mL. Three different laparoscopic systems were used in three hepatectomy cases. In all cases, the fluorescence of the intrahepatic bile ducts in the Glissonian sheath was clearly visualized using the near-infrared laparoscopic system. A small piece of tissue prevented the bile glow; thus, exposure of the Glissonian sheath was necessary for clear FC. This procedure also detected bile leakage from the cut surface of the liver. Intrabiliary ICG administration and near-infrared laparoscopy enabled real-time intrahepatic FC during major hepatectomy.

Classification of left-side hepatolithiasis for laparoscopic middle hepatic vein-guided anatomical hemihepatectomy combined with transhepatic duct lithotomy.

Laparoscopic middle hepatic vein-guided anatomical hemihepatectomy combined with transhepatic duct lithotomy (MATL) is an approach that can substantially improve stone clearance rates while reducing the rate of postoperative biliary fistula formation, residual stone rates, and rates of recurrence. In this study, we classified left-side hepatolithiasis cases into four subtypes based upon the diseased stone-containing bile duct, the middle hepatic vein, and the right hepatic duct. We then investigated the risk associated with different subtypes and evaluated the safety and efficacy of the MATL procedure. In total, 372 patients who underwent left hemihepatectomy for left intrahepatic bile duct stones were enrolled. Based on the distribution of the stones, the cases could be divided into four types. The risk of surgical treatment was compared for the four types and the safety, short-term efficacy, and long-term efficacy of the MATL procedure in the four types of left intrahepatic bile duct stones were studied. Type II was found to be the most likely to cause intraoperative bleeding while type III was likely to cause biliary tract damage and type IV was associated with the highest stone recurrence rate. The MATL procedure did not increase the risk of surgery and was found to reduce the rate of bile leakage, residual stones, and stone recurrence. Left-side hepatolithiasis-associated risk classification is feasible and may represent a viable means of improving the safety and feasibility of the MATL procedure.

Cancer incidence among male construction workers in the Republic of Korea: a standardized incidence ratio analysis, 2009-2015.

Construction workers face an elevated risk for several types of cancer. Nevertheless, there is a lack of large-scale epidemiological studies examining the risk of all cancers in construction workers. This study aimed to investigate the risk of various cancers in male construction workers using the Korean National Health Insurance Service (NHIS) database. We used data from the NHIS database from 2009 to 2015. Construction workers were identified using the Korean Standard Industrial Classification code. We calculated the age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for cancer occurrence in male construction workers compared to all male workers. Compared to all male workers, the SIRs for esophageal cancer (SIR=1.24; 95% CI, 1.07-1.42) and malignant neoplasms of the liver and intrahepatic bile ducts (SIR=1.18; 95% CI, 1.13-1.24) were significantly higher in male construction workers. The SIRs for malignant neoplasms of the urinary tract (SIR=1.19; 95% CI, 1.05-1.35) and non-Hodgkin lymphoma (SIR=1.21; 95% CI, 1.02-1.43) were significantly elevated in building construction workers. The SIR for malignant neoplasms of the trachea, bronchus, and lung (SIR=1.16; 95% CI, 1.03-1.29) was significantly higher in heavy and civil engineering workers. Male construction workers have an increased risk for esophageal cancer, liver cancer, lung cancer, and non-Hodgkin's cancer. Our results indicate that tailored strategies for cancer prevention should be developed for construction workers.

Endoscopic retrieval of a sheared guidewire remnant with microbiopsy forceps from a peripheral intrahepatic bile duct.

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Efficacy of 3D-printed assisted percutaneous transhepatic one-step biliary fistulation combined with rigid choledochoscopy for intrahepatic bile duct stones

This study evaluated the efficacy and safety of three-dimensional printing model-assisted percutaneous transhepatic one-step biliary fistulation (PTOBF) combined with rigid choledochoscopy for intrahepatic bile duct stones in patients with type I bile duct classification. The clinical data of 63 patients with a type I intrahepatic bile duct were reviewed from January 2019 to January 2023; 30 patients who underwent 3D printed model-assisted PTOBF combined with rigid choledochoscopy composed the experimental group and 33 patients who underwent simple PTOBF combined with rigid choledochoscopy composed the control group. Six indicators, including one-stage operation time and clearance rate, final removal rate, bleeding volume, channel size and complications, were observed and analyzed in the two groups. The one-stage and final removal rate in the experimental group was higher than that in the control group (P = 0.034, P = 0.014 versus control group). The time of one-stage operation, bleeding volume, and incidence of complications in the experimental group were significantly lower than those in the control group (P < 0.001, P = 0.039, P = 0.026 versus control group). Compared with simple PTOBF combined with rigid choledochoscopy, 3D printed model-assisted PTOBF combined with rigid choledochoscopy is a safer and more effective method for treating intrahepatic bile duct stones.

Late-onset hemobilia due to pseudoaneurysm rupture after endoscopic ultrasound-guided hepaticogastrostomy.

We report the case of a 65-year-old man who experienced hemobilia due to rupture of a pseudoaneurysm of the left hepatic artery after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS). The patient was diagnosed with pancreatic cancer and underwent endoscopic retrograde cholangiopancreatography for obstructive jaundice. Biliary drainage was converted to EUS-HGS due to tumor invasion in the superior duodenal angle. A partially covered metal stent was placed in the B3 intrahepatic bile duct. The procedure was completed without early complications, but 50days later, the patient developed fever, elevated hepatobiliary enzymes, and shock. Contrast-enhanced computed tomography (CT) showed that the hepatic end of the HGS stent had moved slightly toward the stomach compared to the previous CT. A 6-mm pseudoaneurysm was also observed near the A3 and A4 branches of the left hepatic artery, coinciding with the hepatic end of the EUS-HGS stent. Hemostasis was achieved with coil embolization. Biliary hemorrhage due to rupture of a pseudoaneurysm should be considered in the differential diagnosis of biliary obstruction accompanied by bleeding after EUS-HGS.

Hepatic vascular anatomy and intrahepatic bile duct variation: Donor’s characteristic of liver transplantation in Indonesia

Hepatic vascular anatomy and intrahepatic bile duct variation: Donor’s characteristic of liver transplantation in Indonesia

Population-Attributable Fractions of Personal Comorbidities for Liver, Gallbladder, and Bile Duct Cancers.

We aim to estimate population-attributable fractions (PAF) for 13 comorbidities potentially predisposing to hepatobiliary cancer of hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cancers of the intrahepatic and extrahepatic bile ducts (ICC and ECC), and ampullary cancer. Patients were identified from the Swedish Inpatient Register from 1987 to 2018 and cancers from the Swedish Cancer Registry from 1997 through 2018. PAFs were calculated for each comorbidity-associated cancer using a cohort study design. For male HCC, the major individual comorbidities (PAF > 10) were diabetes, alcohol-related liver disease, and hepatitis C virus infection. For female HCC, diabetes and autoimmune diseases were important contributors. For female GBC, gallstone disease was an overwhelming contributor, with a PAF of 30.57%, which was also important for men. The overall PAF for male ICC was almost two times higher than the female one. For ECC and ampullary cancer, infection of bile ducts was associated with the highest PAF. The 13 comorbidities accounted for 50% or more of the potential etiological pathways of each hepatobiliary cancer except female ICC. The underlying convergent mechanism for these cancers may be chronic inflammation lasting for decades and thus offering possibilities for intervention and disease monitoring.

Laparoscopic Hepp Couinaud for the treatment of Caroli's disease: A case report

Caroli disease is a rare congenital disorder characterized by dilatation of intrahepatic bile ducts. The treatment could correspond to hepatic resection for localized disease.&#x0D; This paper describes a case of Caroli’s disease in a 60 years old female patient, who presented jaundice and diffuse abdominal pain. Further examinations suggested the diagnosis of Caroli disease associated with cholestatic syndrome. We decided to perform a Hepp Couinaud biliodigestive bypass by video laparoscopy with Roux-en-Y reconstruction. There were no immediate complications and no longterm complications after 6 months of follow-up. The VLP biliodigestive bypass in patients with associated cholestatic syndromes should be considered a treatment prior to a more aggressive approach.&#x0D;

Zebrafish ppp1r21 mutant as a model for the study of primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease that progresses to fibrosis and cirrhosis, resulting from the gradual destruction of intrahepatic bile ducts. Exploring genetic variants associated with PBC is essential to understand the pathogenesis of PBC. Here we identify a zebrafish balloon dog (blg) mutant with intrahepatic bile duct branching defects, exhibiting several key pathological PBC-like features, including immunodominant autoantigen PDC-E2 production, cholangiocyte apoptosis, immune cell infiltration, inflammatory activation, and liver fibrosis. blg encodes the protein phosphatase 1 regulatory subunit 21 (Ppp1r21), which is enriched in the liver and its peripheral tissues and plays a vital role in the early intrahepatic bile duct formation stage. Further studies show an excessive activation of the PI3K/AKT/mTOR pathway in the hepatic tissues in the mutant, while treatment with the pathway inhibitor LY294002 and rapamycin partially rescues intrahepatic bile duct branching defects and alleviates the PBC-like symptoms. These findings implicate the potential role of the Ppp1r21-mediated PI3K/AKT/mTOR pathway in the pathophysiology of PBC.

Incidence and Mechanism of Refractory Postoperative Cholangitis After Hepatectomy with Hepaticojejunostomy

IntroductionMalignant tumors, such as hilar cholangiocarcinoma, have shown improved long-term outcomes, and measures to prevent late postoperative complications are important. Postoperative cholangitis after hepatectomy with hepaticojejunostomy (HHJ) may occur and can significantly decrease the quality of life. However, there are few reports on the incidence and pathogenesis of postoperative cholangitis after HHJ. MethodsWe retrospectively reviewed 71 cases post HHJ at Tokyo Medical and Dental University Hospital from January 2010 to December 2021. Cholangitis was diagnosed using the Tokyo Guideline 2018. Cases due to tumor recurrence around the hepaticojejunostomy (HJ) were excluded. Patients with three or more episodes of cholangitis were classified as the “refractory cholangitis group” (RC group). RC group patients were divided into a “stenosis group” and “non-stenosis group” according to intrahepatic bile duct dilatation at the onset of cholangitis. Their clinical characteristics and risk factors were analyzed. ResultsCholangitis occurred in 20 patients (28.1%), with 17 (23.9%) in the RC group. Most patients in the RC group developed their first episode within the first postoperative year. The stenosis group consisted of 6 patients, and their cholangitis was treated with repeated anastomotic dilatation and stent replacement. In the non-stenosis group, cholangitis was relatively mild and treated with antibiotics. Hepatobiliary scintigraphy for these cases showed bile congestion in the jejunum near the site of the hepaticojejunostomy. ConclusionThere are two types of postoperative cholangitis, each with different pathogenesis and treatment. It is essential to assess anastomotic stenosis early and provide the necessary treatment.