Bile Duct Injury Research Articles

The Significance of Biliary Anatomical Variation as a Key Indicator in Laparoscopic Bile Duct Injuries

Introduction: The science of Gastrointestinal (GI) endoscopy is the science and art of millimeters that has marvelously evolved over the past 30 years. Cholecystectomy, most of which is done laparoscopically, is one of the most common procedures performed today (approximately 750,000 cases are performed annually in the USA) and is considered relatively safe. However, laparoscopic cholecystectomy is associated with bile duct injuries. Several studies examining bile duct injuries have found significant rates of complication (0.39%---1.5%, that comes roughly to over 3,000 patient per year). Therefore, bile duct injuries are commonly encountered, and a clear understanding of the extensive variation in biliary anatomy is imperative to appropriately and successfully manage this common clinical problem to ultimately provide the highest level of patient care.

Fenestrating Versus Reconstituting Subtotal Cholecystectomy: Systematic Review and Meta-Analysis on Bile Leak, Bile Duct Injury, and Outcomes.

Symptoms of gallstone disease are the most common reason for cholecystectomy. Fenestration reduces the likelihood of severe inflammation or scarring after normal treatments are used, and it also enhances control over bile outflow. The goal of reconstituted cholecystectomy is to lessen symptoms like pain and jaundice without undergoing the high-risk procedures associated with more invasive procedures. The reconstituted and fenestrated procedures were assessed by a meta-analysis and systematic review. Of the five studies, 189 (34.2%) had a reconstituted subtotal cholecystectomy, and 363 (65.8%) had a fenestrated subtotal cholecystectomy, which had populations from the United States of America, the United Kingdom, Japan, and Turkey. Two individuals from three trials had bile duct injury, according to three studies. Whereas the fenestrated group reported no bile injury from 236 individuals (0%), the reconstituted group reported two bile duct injuries from 100 patients (2%). The incidence was found to be lower in the fenestrated group (OR 10.81; CI 95% 1.03-113.65; p = 0.39; I2 = 0%) than in the reconstituted group. Four studies revealed 92 cases of bile leaks: 19 out of 155 cases (12.3%) were reconstituted, and 73 out of 351 cases (20.8%) were fenestrated. Between the two groups, there was a significant difference in bile leakage (OR 0.72; CI 95% 0.23-2.32; p = 0.03; I2 = 66%). Two studies reported the establishment of fistulas following surgery in 58 patients in the reconstituted group (5.2%) and 120 patients in the fenestrated group (2.5%) (p = 0.56, I2 = 0%, and OR 0.65; CI 95% 0.12-3.38); however, there was no statistically significant difference between the groups. Following a fenestrated partial cholecystectomy, postoperative bile leakage, fistula development, wound infection, and retained stones are more prevalent. Additionally, we saw that the fenestrated method was being used more frequently for post-operative endoscopic retrogradecholangiopancreatography (ERCP). The subtotal cholecystectomy technique used should be chosen according to the surgeon's comfort level and experience with the various techniques and intraoperative findings, even if the reconstituted procedure could be preferred when feasible. To completely understand the role of each method in the general surgeon's toolkit for treating complex gallbladder (GB) patients, longer-term follow-up studies are still necessary.

Extracellular vesicles of Clonorchis sinensis promote the malignant phenotypes of cholangiocarcinoma via NF-κB/EMT axis.

Clonorchis sinensis infection is an important risk factor for cholangiocarcinoma (CCA). It has been reported that extracellular vesicles (EVs) are involved in the parasite-host interaction, and EVs of C. sinensis (CsEVs) can contribute to biliary injuries and inflammation. However, uncertainty surrounds the function of CsEVs in the progression of CCA. In this study, differential ultracentrifugation was used to separate CsEVs from the culture supernatant of C. sinensis adult worms, and they were then identified by transmission electron microscopy, nanoparticle tracking analysis and proteome assays. CCK8, EdU-488 and colony formation assays were used to explore the effect of CsEVs on the proliferation of CCA cells in vitro. Wound healing assays, transwell assays and in vivo lung metastasis model were conducted to evaluate the migration and invasion abilities. Moreover, the involvement of EMT process, as well as NF-κB and ERK signaling pathway was assessed. Results showed that CsEVs were successfully isolated and could be taken up by CCA cells, which promoted proliferation by accelerating cell cycle progression. In addition, CsEVs could facilitate cell metastasis by triggering the epithelial-mesenchymal transition (EMT). Mechanistically, activation of NF-κB signaling pathway was involved in the CsEVs-mediated EMT, which could be reversed partly by BAY 11-7082 (an inhibitor of NF-κB). In conclusion, these findings suggested that CsEVs could induce the aberrant proliferation and metastasis of CCA cells by stimulating the NF-κB/EMT axis, providing a novel theoretical explanation for liver fluke-associated CCA.

Current application of artificial intelligence in laparoscopic cholecystectomy

Recent advances in artificial intelligence (AI) have sparked a surge in the application of computer vision (CV) in surgical video analysis. Surgical complications often occur due to lapses in judgment and decision-making. In laparoscopic cholecystectomy, achievement of the critical view of safety is commonly advocated to prevent bile duct injuries. However, bile duct injuries rates remain stable, probably due to inconsistent application or a poor understanding of critical view of safety. Advances in AI have made it possible to train algorithms that identify anatomy and interpret the surgical field. AI-based CV techniques may leverage surgical video data to develop real-time automated decision support tools and surgeon training systems. The effectiveness of CV application in surgical procedures is still under early evaluation. The review considers the commonly used deep learning algorithms in CV and describes their usage in detail in four application scenes, including phase recognition, anatomy detection, instrument detection and action recognition in laparoscopic cholecystectomy. The MedLine, Scopus, and IEEE Xplore databases were searched for publications up to 2024. The keywords used in the search were “laparoscopic cholecystectomy”, “artificial intelligence”. The currently described applications of CV in laparoscopic cholecystectomy are limited. Most current research focus on the identification of workflow and anatomical structure, while the identification of instruments and surgical actions is still awaiting further breakthroughs. Future research on the use of CV in laparoscopic cholecystectomy should focus on application in more scenarios, such as surgeon skill assessment and the development of more efficient models.

African American Females are More Vulnerable to Develop Biliary Injury in NAFLD (Nonalcoholic fatty liver disease) Patients – A Single Institute Experience

Abstract Introduction/Objective Chronic alcohol exposure alone may take decades to induce severe liver disease, yet when combined with elements such as the Western diet, liver pathogenesis accelerates, resulting in earlier symptoms. Identifying the specific contributions of alcohol, diet, and other factors to liver disease is challenging, despite the availability of diagnostic tools like patient histories, liver enzyme tests, imaging, and biopsies. Methods/Case Report This study seeks to detail the liver disease profile of patients who underwent liver biopsies in 2022. Comprehensive profiles were created by retrieving liver biopsy specimens and associated diagnostic data from electronic medical records. Two independent pathologists analyzed the biopsy slides, looking for liver damage associated with alcohol consumption and Western diet influences. We employed enhanced staining techniques to better associate specific types of liver damage with demographic variables. The data analysis was conducted using GraphPad Prism 9 for robust statistical evaluation. Results (if a Case Study enter NA) The research included 88 participants—41 males and 47 females, with average ages of 56 and 62 respectively. The predominant diagnosis was fatty liver disease, with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) accounting for 26% of cases, and alcoholic liver disease (ALD) making up 10%. The NAFLD/NASH group (n=23) consisted mainly of African Americans (n=15) and Caucasians (n=8). Among these, African Americans showed a significantly greater ductular reaction and portal inflammation (p<0.05). Conversely, no notable differences in portal fibrosis and bile stasis were observed between these groups. Notably, African American females (n=11) demonstrated more severe pathological features compared to Caucasian females (n=6), including elevated levels of ductular reaction, fibrosis, portal inflammation, and bile stasis (p<0.05), suggesting a higher vulnerability to biliary injuries. Conclusion The study highlights the complex interplay between lifestyle factors and liver disease development and emphasizes the need for precise diagnostic strategies that consider these multifactorial influences. Additionally, it reveals ethnic disparities in the pathology of NAFLD, advocating for further research into their causes and implications for clinical management. Future investigations should focus on race and gender-specific factors and adapt local healthcare strategies to effectively manage the escalating burden of liver disease.

Histologic Patterns of Ribociclib-induced Liver Injury

Abstract Introduction/Objective Ribociclib, a cyclin dependent kinase (CDK) 4/6 inhibitor, used in the treatment of advanced breast carcinomas, can cause liver injury, often manifesting as elevated liver enzymes. However, the histologic patterns of liver injury caused by Ribociclib have not been well-documented. Our study aims to explore these patterns in patients undergoing Ribociclib treatment. Methods/Case Report Five female patients receiving Ribociclib treatment for breast carcinomas and undergoing liver biopsy post-transaminitis in the past seven years (2017-2024) were identified using our institution’s electronic medical record. Clinical information was collected, and liver biopsies were reviewed for histologic injury patterns. Results (if a Case Study enter NA) The mean age of the patients was 47 years (range 38-68). All patients had liver enzyme abnormalities after starting with Ribociclib: mean time to peak of ALT and AST was 75 days (range 36-125). Mean peak enzyme levels (IU/L) for ALT and AST were 685 and 420, respectively. Liver biopsy showed an acute hepatitis pattern of injury in all five patients: centrizonal confluent necrosis (n=3) and lobular spotty necrosis (n=2). Other findings included: mild cholestasis (n=1), interface hepatitis (n=2), focal bile duct injury (n=2), and mild macrovesicular steatosis without steatohepatitis (n=1). Portal inflammation was mild to moderate, comprising a mixed lymphoplasmacytic infiltrate. One patient had moderate periportal fibrosis without bridging. Ribociclib was withdrawn in all patients; three patients received prednisolone treatment. Three patients were rechallenged with Abemaciclib and two with Palbociclib. All patients had resolution of liver function tests after cessation of Ribociclib therapy. Mean time to normalization of ALT and AST was 46 days (range 30-72) and 62 days (range 30-96), respectively, after holding Ribociclib. Conclusion Ribociclib predominantly causes an acute hepatitis pattern of liver injury and of varying severity. Drug cessation, with or without steroid therapy, and switching to a less hepatotoxic CDK 4/6 inhibitor can be sufficient to restore normal liver function. Screening for liver dysfunction with baseline enzyme tests prior to Ribociclib treatment, as well as serial testing to trend enzyme levels, may help prevent severe liver injury.

Internal Drainage: An Interim Alternative to External Biliary Fistula in the Management of Postcholecystectomy Bile Duct Injury

Internal Drainage: An Interim Alternative to External Biliary Fistula in the Management of Postcholecystectomy Bile Duct Injury

Turmeric supplement-associated hepatitis: a clinicopathological series of 11 cases highlighting pan-lobular and zone 3 injury.

Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over-the-counter turmeric supplements can cause drug-induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements. We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37-66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan-lobular and three zone 3-predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement-associated liver injury to be probable (eight cases) and possible (three). Histological features in the 'possible' cases were consistent with drug-induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over-the-counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric.

Bailout for the Difficult Gallbladder: Subtotal vs. Open Cholecystectomy-A Retrospective Tertiary Care Center Experience.

Background and Objectives: A difficult gallbladder anatomy augments the risk of bile duct injuries (BDIs) and other complications during a laparoscopic cholecystectomy. This study compares the outcomes of a laparoscopic subtotal cholecystectomy (LSTC) and open total cholecystectomy (OTC) for difficult cholecystectomies. Materials and Methods: This retrospective analysis of gallbladder procedures (LSTC or OTC) from 2016 to 2023 examined patient demographics, surgical details, and postoperative results. The primary outcome was the incidence of a BDI. Secondary outcomes included operative duration, blood loss, and postoperative complications. Results: Seventy-one patients were included in the study. Of them, 59.2% (n = 42) underwent an LSTC and 44.6% (n = 29) underwent an OTC. The LSTC cohort was more likely to have a day-surgery case with a same-day discharge (33.3% vs. 0%, p = 0.009), less blood loss (71.4 ± 82.26 vs. 184.8 ± 234.86, p = 0.009), and a shorter operative duration (187.86 ± 68.74 vs. 258.62 ± 134.52 min, p = 0.008). Furthermore, BDI was significantly lower in the LSTC group (2.4% vs. 17.2%, p = 0.045). However, there were no significant differences between the two groups concerning intraoperative drain placement, peri-cholecystic fluid collection, bile leak, and other complications (p > 0.05). Conclusions: LSTC is a safe and effective alternative to OTC for challenging gallbladder cases. Further studies with larger sample sizes and longer follow-up periods as well as different study designs are warranted.

Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome.

Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.

Chyle leakage after laparoscopic cholecystectomy in a patient with duplicated cystic ducts: A case report and literature review.

Laparoscopic cholecystectomy (LC) is widely performed as a standard treatment for cholelithiasis, and chyle leakage after LC has rarely been reported. Duplicated cystic ducts draining a single gallbladder is an extraordinarily rare variation. We presented a case of chyle leakage after LC in a 53-year-old female with a rare variation of duplicated cystic ducts. Chyle leakage and duplicated cystic ducts. Conservative treatment including lipid intake and constant drainage. After 24 days of conservative treatment, the patient recovered and had no further troubles during the 3-month follow-up. There may be a potential relationship between anatomic variants of the extrahepatic bile ducts and those of the lymphatic system. When anatomic variations of the extrahepatic bile ducts are encountered, vigilance for lymphatic system injuries is as important as vigilance for bile duct injuries. Conservative therapy is the first choice for postoperative chyle leakage, and surgical intervention should be considered in cases with high-volume chyle leakage.

Bile reinfusion, a novel alternative for nutritional optimization after bile duct injury

Bile reinfusion, a novel alternative for nutritional optimization after bile duct injury

Clinical and patient-reported outcomes following subtotal cholecystectomy: 10-year single-institution experience

ObjectiveSubtotal cholecystectomy provides a safe, bail-out alternative for difficult gallbladders. However, long-term outcomes comparing fenestrating and reconstituting subtotal cholecystectomy subtypes remain underexplored. MethodsThis retrospective cohort included patients who underwent subtotal cholecystectomy between 2010 and 2020 within a single hospital system. Subtotal cholecystectomy was identified by parsing operative notes for keywords. Demographic and clinical variables were collected by manual review. Patient-reported outcomes were collected via phone using an abbreviated Gastrointestinal Quality-of-Life Index. ResultsWe identified 218 subtotal cholecystectomies, with 113 (51.8%) fenestrating subtotal cholecystectomy and 105 (48.2%) reconstituting subtotal cholecystectomy and a median follow-up of 63 months (interquartile range 27–106). Rates of bile duct injury (0.9% vs 1.0%; P > .99), bile leak (10.6% vs 9.5%; P > .99), and 30-day readmission (7.6% vs 8.0%; P > .99) did not differ between fenestrating and reconstituting subtotal cholecystectomy. For fenestrating subtotal cholecystectomy, the postoperative bile leak rate decreased fourfold when cystic duct closure was achieved (6.0% vs 24.1%; P = .012). Subtotal cholecystectomies completed laparoscopically had fewer postoperative bile leaks (2.9% vs 16.8%; P = .001), fewer wound complications (4.8% vs 13.3%; P = .035), and decreased length of stay (7.00 ± 9.07 vs 10.15 ± 13.50 days; P < .001) compared with open operations. The survey response rate was 38.9% (n = 51/131); 47 patients (92.2%) did not report recurrent biliary pain or postprandial nausea or vomiting, but 19 patients (37.2%) reported dietary restriction. Long-term completion cholecystectomy rate was 0.9%. ConclusionGiven no notable difference in postoperative or quality of life outcomes between subtotal cholecystectomy subtypes, consideration of technique depends on intraoperative conditions. Cystic duct closure during fenestrating subtotal cholecystectomy and laparoscopic completion of subtotal cholecystectomy are associated with improved postoperative outcomes.

Intragallbladder versus intravenous indocyanine green (ICG) injection for enhanced bile duct visualization by fluorescent cholangiography during laparoscopic cholecystectomy: a retrospective cohort study.

Iatrogenic bile duct injuries (BDIs) prevention during laparoscopic cholecystectomy (LC) relies on meticulous anatomical dissections through direct visualization. Near-infrared fluorescence (NIRF) with indocyanine green (ICG) improves the visualization of extrahepatic biliary structures. Although ICG can be administered either intravenously or intragallbladder, there remains uncertainty regarding the optimal method for different patient populations. This study sought to assess the suitability of each method for specific patient groups. Between October 2021 and May 2022, 59 consecutive patients underwent fluorescence-guided LC at West China Hospital of Sichuan University. Among them, 32 patients received an intravenous injection of ICG (10 mg) 10 to 12 hours prior to surgery (Group A: the intravenous group), while 27 patients received an intragallbladder injection of ICG (10 mg) (Group B: the intragallbladder group). Baseline clinical factors, inclusion criteria, and measurements of parameters and complications were assessed. Data were retrospectively collected and analyzed to evaluate the comparability of the two groups and the clinical outcomes. Groups A and B included 32 patients (18 males, 14 females), and 27 patients (13 men, 14 women), respectively. In our statistical analysis, significant differences were observed in preoperative diagnoses between the two groups (P=0.041), but the majority of other baseline clinical factors were comparable. Notably, no statistically significant differences were found in complication rates. However, Group A had a shorter operative time (60.38±9.35 vs. 66.78±9.88 min, P=0.01) and superior bile duct fluorescence (P=0.04) than Group B. Interestingly, fluorescence was not observed in impacted gallbladder stones in Group B. Additionally, patients with cirrhosis (P=0.008) and fatty liver (P=0.005) in Group B had higher common bile duct-to-liver ratios (BLRs) than those in Group A. ICG fluorescence cholangiography allows to visualize extrahepatic biliary anatomical structures with both administration methods. However, the efficacy of bile duct fluorescence varies with different administration routes in diverse patient populations. Hence, appropriate administration route selection for ICG should be tailored to individual patients.

Application of indocyanine green during laparoscopic cholecystectomy in elderly and senile patients

Aim. To evaluate an effect of fluorescence cholangiography for intraoperative identification of extrahepatic bile ducts on the treatment outcomes of patients with cholelithiasis.Materials and methods. The study included 71 cholelithiasis patients who underwent laparoscopic cholecystectomy with fluorescence cholangiography and 69 cholelithiasis patients who underwent standard laparoscopic cholecystectomy. The study analyzed intraoperative damage of extrahepatic bile ducts and arteries, duration of surgery, conversion rate, need for colleague assistance, incidence of postoperative complications, hospital length of stay, and outcomes.Results. Fluorescence of the vesicular duct was achieved in 100% of patients, of the common bile duct – in 91%, and of the common hepatic duct – in 64%. A correlation between the number/type of complications and the application of ICG-diagnostics was found statistically significant (p &lt;0.001, p = 0.012), thereby indicating the advantages of the method. The colleague-surgeon assistance was required in the ICG group 35 times less than in the standard surgery group (OR = 0.029; 95% CI = 0.003–0.319). A 34-minute reduction in surgery duration (linear regression) can be expected when performing ICG-guided surgery.Conclusion. The application of fluorescence cholangiography reduces the probability of postoperative complications, in particular, biliary leakage with the necessity of reoperation. Due to the method, a surgeon appears able to complete the operation independently without colleague assistance. Treatment outcomes, incidence of bile duct injuries, and conversion rate are yet to be investigated.

Day-case laparoscopic cholecystectomy in the management of gallbladder disease: a literature review.

Day-case laparoscopic cholecystectomy (DCLC) has gained traction globally due to its benefits, including shorter hospital stays, reduced costs, and enhanced patient experience. While concerns about patient safety, particularly related to bleeding and bile duct injury persist, the literature supports the efficacy and advantages of DCLC highlighting the need for its wider adoption in healthcare settings to optimise resources and improve patient outcomes. This was a literature review that aims to assess the feasibility and safety of day-case laparoscopic cholecystectomy for symptomatic gallstone patients, focusing on incidence and aetiology of unexpected admissions and readmissions, as well as conversion-to-open rates. PubMed was searched for all studies focusing on DCLC between 2014 and 2024. The timeframe was specifically selected to identify recent trends and practices in this evolving field. By focusing on this specific period, the review aims to provide a comprehensive analysis of current practices, emerging trends, and the evolving standard of care in this area. This review highlights that the main causes of unexpected admission post DCLC were postoperative nausea, vomiting, and pain, while the implementation of anaesthetic pathways notably increased day-case rates. Studies addressing complication rates postoperatively consistently found no significant difference between day-case and in-patient procedures. DCLC for symptomatic gallstone patients is supported by research as safe and effective, with high success rates and patient satisfaction. Studies show minimal complications and acceptable readmission rates, suggesting that DCLC can be the standard approach for selective patients, improving outcomes and healthcare efficiency.

Application of three-dimensional visualization technology in early surgical repair of bile duct injury during laparoscopic cholecystectomy

ObjectiveThis study aimed to explore the application value of three-dimensional (3D) visualization technology in the early surgical repair of bile duct injury during laparoscopic cholecystectomy (LC).MethodsA retrospective analysis was conducted on the clinical data of 15 patients who underwent early surgical repair of bile duct injury during LC with the assistance of 3D visualization technology at the Hepatobiliary Surgery Department of Ningxia Hui Autonomous Region People’s Hospital from January 2019 to December 2022. Postoperative efficacy and long-term follow-up outcomes were summarized.ResultsBefore the repair surgery, 15 cases of bile duct injury during LC were evaluated using 3D visualization technology according to the Strasberg-Bismuth classification: 2 cases of type C, 4 of type E1, 3 of type E2, 3 of type E3, and 3 of type E4. Intraoperative findings were consistent with the 3D visualization reconstruction results, and all patients successfully underwent hepaticojejunostomy using Roux-en-Y anastomosis guided by the 3D visualization navigation. The time interval between LC and bile duct repair surgery ranged from 5 to 28 (14.2 ± 9.7) days. The surgical time was between 120 and 190 (156.40 ± 23.92) min, and estimated blood loss ranged from 80 to 250 (119.66 ± 47.60) mL. The length of hospital stay ranged from 12 to 25 days (median: 16 days). One patient experienced mild bile leakage after the operation, which healed with conservative treatment. All patients were followed up for 12–56 months (median: 34 months) without any loss to follow-up. During the follow-up period, no complications, such as anastomotic stricture or stone formation, were observed.ConclusionThe application of 3D visualization technology for preoperative evaluation and intraoperative navigation can accurately and effectively facilitate early surgical repair of bile duct injury during LC and has clinical value for promotion and application.

The role of 2ʹ–5ʹ-oligoadenylate synthase-like protein (OASL1) in biliary and hepatotoxin-induced liver injury in mice

Following an injury, the liver embarks on a process that drives the accumulation and reformation of the extracellular matrix, leading to hepatic fibrosis. Type I interferons (IFNs), including IFN-α and IFN-β, play a crucial role in averting chronic liver injury through the activation of IFN-stimulated genes (ISGs), which are instrumental in sculpting adaptive immunity. The role of 2ʹ–5ʹ-oligoadenylate synthase-like protein 1 (OASL1), an antiviral ISG, in the context of liver fibrosis remains to be elucidated. To elicit liver fibrosis, a diet containing 0.1% diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4) were employed to induce cholestatic- and hepatotoxin-mediated liver fibrosis, respectively. Histological analyses of both models revealed that OASL1−/− mice exhibited reduced liver damage and, consequently, expressed lower levels of fibrotic mediators, notably α-smooth muscle actin. OASL1−/− mice demonstrated significantly elevated IFN-α and IFN-β mRNA levels, regulated by the IFN regulatory factor 7 (IRF7). Additionally, OASL1−/− ameliorated chronic liver fibrosis through the modulation of nuclear factor-κB (NF-κB) signaling. The effect of OASL1 on type I IFN production in acute liver damage was further explored and OASL1−/− mice consistently showed lower alanine transaminase levels and pro-inflammatory cytokines, but IFN-α and IFN-β mRNA levels were upregulated, leading to amelioration of acute liver injury. Additionally, the study discovered that F4/80-positive cells were observed more frequently in OASL1−/− CCl4 acutely treated mice. This implies that there is a significant synergy in the function of macrophages and OASL1 deficiency. These results demonstrate that in instances of liver injury, OASL1 inhibits the production of type I IFN by modulating the NF-κB signaling pathway, thereby worsening disease.

Gly-β-MCA is a potent anti-cholestasis agent against “human-like” hydrophobic bile acid-induced biliary injury in mice

Cholestasis is a chronic liver disease with limited therapeutic options. Hydrophobic bile acid-induced hepatobiliary injury is a major pathological driver of cholestasis progression. This study investigates the anti-cholestasis efficacy and mechanisms of action of glycine-conjugated β-muricholic acid (Gly-β-MCA). We use female Cyp2c70 KO mice, a rodent cholestasis model that does not produce endogenous muricholic acid (MCA) and exhibits a “human-like” hydrophobic bile acid pool and female-dominant progressive hepatobiliary injury and portal fibrosis. The efficacy of Gly-β-MCA and ursodeoxycholic acid (UDCA), the first line drug for cholestasis, on cholangiopathy and portal fibrosis are compared. At a clinically relevant dose, Gly-β-MCA shows comparable efficacy as UDCA in reducing serum transaminase, portal inflammation and ductular reaction, and better efficacy than UDCA against portal fibrosis. Unlike endogenous bile acids, orally administered Gly-β-MCA is absorbed at low efficiency in the gut and enters the enterohepatic circulation mainly after microbiome-mediated deconjugation, which leads to taurine-conjugated MCA enrichment in bile that alters enterohepatic bile acid pool composition and reduces bile acid pool hydrophobicity. Gly-β-MCA also promotes fecal excretion of endogenous hydrophobic bile acids and decreases total bile acid pool size, while UDCA treatment does not alter total bile acid pool. Furthermore, Gly-β-MCA treatment leads to gut unconjugated MCA enrichment and reduces gut hydrophobic lithocholic acid (LCA) exposure. In contrast, UDCA treatment drives a marked increase of LCA flux through the large intestine. In conclusion, Gly-β-MCA is a potent anti-cholestasis agent with potential clinical application in treating human cholestasis.

The Role of ICG-Guided Fluorescent Mode in Boosting the Learning Curve of Laparoscopic Cholecystectomy.

Background: The most common therapy for gallstones is laparoscopic cholecystectomy (LC). How to help young residents avoid bile duct injuries (BDI) during surgery and grasp LC seems to be a paradox. Methods: We retrospectively reviewed 145 cases of LC operated by two residents under indocyanine green (ICG)-guided mode or normal LC procedures to illustrate the role of ICG mode in boosting the LC learning curve. The clinic data were analyzed by logistic regression, receiver operator curve tests, Cumulative Sum (CUSUM), and Risk-Adjusted Cumulative Sum (RA-CUSUM) analysis. Results: The operation failure rate is similar. However, operation time under ICG mode is shorter than that under normal mode. The peak at the 49th case represented the normal resident's complete mastery of the surgery, while the peak point of ICG mode appeared at the 36th case in the fitting curve. The most significant cumulative risk (peak point) of operation failure of LC was at the 35th case in ICG LC mode, while it appeared in the 49th in normal LC mode. Conclusions: Owing to the advantage of real-time imaging and the stable success rate of cholangiography, ICG-guided LC helps residents shorten the operation time, boost the learning curve, and manage to control the operation failure rate.