Search Results (673)

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article

Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article

Background: Liver fibrosis, a consequence of various chronic liver diseases, is characterized by excessive accumulation of extracellular matrix (ECM), leading to impaired liver function and potentially progressing to cirrhosis or hepatocellular carcinoma. The molecular mechanisms underlying liver fibrosis are complex and not fully understood. In vivo experiments are essential for studying the molecular mechanisms of the disease. However, the diverse principles behind mouse modeling techniques for liver fibrosis can complicate the elucidation of specific fibrotic mechanisms. Methods: Five distinct liver fibrosis models were utilized: CONTROL, NASH (non-alcoholic steatohepatitis), BDL (bile duct ligation), TAA (thioacetamide), and CCl₄ (carbon tetrachloride). Patents for these drugs were reviewed using Patentscope^® and Worldwide Espacenet^®. ScRNA-seq was performed to analyze and compare the cellular and molecular differences in these models. Results: The analysis revealed that, particularly in the drug-induced fibrosis models, hepatic stellate cells (HSCs), Kupffer cells, and T-cell subsets exhibit distinct regulatory patterns and dynamic remodeling processes across different liver fibrosis models. These findings highlight the heterogeneity of immune responses and extracellular matrix (ECM) remodeling in various models, providing important insights into the complex mechanisms underlying liver fibrosis. Conclusions: The study enhances our understanding of liver fibrosis development and provides valuable insights for selecting the most representative animal models in future research. This comprehensive analysis underscores the importance of model-specific immune responses and ECM remodeling in liver fibrosis. Full article

Introduction: Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) is now widely regarded as a valuable aid in decision-making for complex hepatobiliary procedures, with increasing support from recent studies. Methods: We performed a systematic review following PRISMA guidelines, utilizing PubMed, CINAHL, and EMBASE databases to locate studies on the perioperative use ICG in pediatric hepatobiliary surgeries. Two independent reviewers assessed all articles for eligibility based on predefined inclusion criteria. We collected data on study design, patient demographics, surgical indications, ICG dosing, timing of ICG injection, and perioperative outcomes. Results: Forty-three articles, including 930 pediatric patients, from 1989 to 2025 met the inclusion criteria for narrative synthesis in our systematic review, of which 22/43 (51.2%) were retrospective studies, 15/43 were case reports (34.9%), 3/43 (7.0%) were experimental studies, and the other three were prospective comparative studies (7.0%). The current clinical applications of ICG in hepatobiliary pediatric surgery include bile duct surgery (cholecystectomy, choledochal cyst, biliary atresia), reported in 17 articles (39.5%), liver tumor resection, reported in 15 articles (34.9%), liver transplantation, reported in 6 articles (14.6%), and liver function determination, reported in 5 articles (12.2%). Conclusions: ICG fluorescence navigation in pediatric hepatobiliary surgery is a highly promising and safe technology that allows for the intraoperative localization of anatomic biliary structures, aids in the identification and resection of liver tumors, and can accurately determine hepatic function. The lack of comparative and prospective studies, and the variability of the dose and timing of administration are the main limitations. Full article

Two geriatric (>9 years old) dogs presented with vomiting, depression, and anorexia and were diagnosed with extrahepatic biliary obstruction (EHBO) secondary to ruptured gallbladder mucoceles. Diagnosis was based on serum biochemical analysis, abdominal radiography, and ultrasonography, which revealed gallbladder rupture, peritonitis, and common bile duct dilation. Both dogs underwent emergency surgical intervention involving cholecystectomy and choledochal stent placement in the common bile duct without cholecystojejunostomy or cholecystoduodenostomy. Postoperatively, the clinical symptoms and serum chemistry values improved, and both dogs survived without recurrence for over one year. These cases demonstrate that choledochal stenting can be an effective adjunct to cholecystectomy for managing EHBO in dogs with ruptured gallbladder mucoceles, potentially preventing reocclusion and promoting recovery, especially when histopathological evaluation is not feasible in clinical settings. However, persistent elevation of liver enzymes may occur postoperatively, necessitating prolonged monitoring and medical management in some cases. Full article

Pancreatic cancer is an aggressive malignancy, with a current 5-year survival rate in the United States of approximately 13.3%. Although the current standard for resectable pancreatic cancer most commonly includes neoadjuvant chemotherapy prior to a curative resection, surgery, in the majority of patients, has historically been palliative. The latter interventions include open or laparoscopic bypass of the bile duct or stomach in cases of obstructive jaundice or gastric outlet obstruction, respectively. Non-surgical interventional therapies started with percutaneous transhepatic biliary drainage (PTBD), both as a palliative maneuver in unresectable patients with obstructive jaundice and to improve liver function in patients whose surgery was delayed. Likewise, interventional radiologic techniques included the placement of plastic and ultimately self-expandable metal stents (SEMSs) through PTBD tracts in patients with unresectable cancer as well as percutaneous cholecystostomy in patients who developed cholecystitis in the context of malignant obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) and stent placement (plastic/SEMS) were subsequently used both preoperatively and palliatively, and this was followed by, or undertaken in conjunction with, endoscopic gastro-duodenal SEMS placement for gastric outlet obstruction. Although endoscopic ultrasound (EUS) was initially used to cytologically diagnose and stage pancreatic cancer, early palliation included celiac block or ablation for intractable pain. However, it took the development of lumen-apposing metal stents (LAMSs) to facilitate a myriad of palliative procedures: cholecystoduodenal, choledochoduodenal, gastrohepatic, and gastroenteric anastomoses for cholecystitis, obstructive jaundice, and gastric outlet obstruction, respectively. In this review, we outline these procedures, which have variably supplanted surgery for the palliation of pancreatic cancer in this rapidly evolving field. Full article

This case report describes index pancreatoduodenectomy in a 32-year-old male following a close-range gunshot wound to the abdomen, with consequent 4 cm pancreatic head defect, duodenal and common bile duct perforation, right kidney laceration, and through-and-through inferior vena cava (IVC) injury. Although standard trauma protocols often favor damage control surgery (DCS) with delayed reconstruction in unstable patients, this patient’s hemodynamic stability—attributed to retroperitoneal self-tamponade—enabled a single-stage definitive approach. The rationale for immediate reconstruction was to prevent the risks associated with delayed management, such as ongoing pancreatic and biliary leakage, chemical peritonitis, and subsequent sepsis or hemorrhage. This case highlights that, in select stable patients with severe pancreaticoduodenal trauma, immediate pancreatoduodenectomy may be preferable to DCS, provided care is delivered in a high-volume hepatopancreaticobiliary (HPB) center with appropriate expertise and resources. Full article

In the management of cholangiocarcinoma, effective biliary drainage and accurate diagnosis are vital to allow further treatment. Confirmation of tissue diagnosis and molecular characterization is also required to guide future treatment options including surgery and chemotherapy as well as the possible use of personalized treatments that target specific mutations present within individual tumours. Initial CT or MRI scans may be followed by endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) to obtain tissue samples. However, these methods often fall short due to difficulty in accessing entire bile duct strictures. SpyGlass cholangioscopy can improve diagnosis, yet may fail to provide sufficient tissue for molecular characterization. Here we present a perspective on the development of snake-like agile robots with integrated optical imaging and Raman spectroscopy. These robots could improve the mapping of the biliary tree and the precision of biopsy collection and allow tissue analysis in situ, as well as facilitating stenting to restore the flow of bile. A multidisciplinary approach that brings together clinicians, pathologists, and engineers is required to develop these new robotic technologies and improve patient outcomes. Full article

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by bile duct inflammation and fibrosis, leading to cirrhosis and liver failure. Current therapies are limited to symptom management, with no approved treatments targeting fibrosis. We have identified the MAP kinase-activated protein kinase 2 (MK2) pathway as a potential therapeutic target for treating PSC due to its role in promoting inflammatory cytokine production and activation of fibroblasts. Thus, MDR2 knockout mice were treated therapeutically with MK2 inhibitors, which led to significantly reduced hepatic inflammation and fibrosis. Liver enzymes, collagen 1A1, and fibronectin were decreased in serum with MK2 inhibitor treatment. Furthermore, the production of IL-6, TNFα, CXCL5, collagen 1A1, and fibronectin was decreased in liver tissues and liver stellate cells, whereas the production of IL-10, G-CSF, and IL-22 was increased. MDR2KO mice treated with IL-22 also showed improvements in inflammation and fibrosis, along with increased IL-10 and G-CSF production. Taken together, we identified both a direct mechanism of MK2 regulation of fibrotic factors and an indirect cytokine-mediated mechanism whereby the levels of IL-22, IL-10, and G-CSF were increased with MK2 inhibition and contributed to decreased levels of fibrotic factors. These data suggest that the MK2 pathway is a promising treatment target for PSC. Full article

Background: Cholangiocarcinoma, malignancies arising from the intrahepatic and extrahepatic bile ducts, has increased in incidence in the United States over the past few decades. The reported incidence of cholangiocarcinomas is high, particularly in specific racial groups such as Asian and Pacific Islander patients. Race also significantly impacts disparities in healthcare utilization and clinical outcomes. Our study focused on the impact of race on admission, clinical outcomes, and disposition of cholangiocarcinoma. Methods: We performed a retrospective analysis of cholangiocarcinoma-related hospital admissions, using the National Inpatient Sample for the year 2022. Patients were stratified according to race into the following groups: White, African American, Hispanic, Asian or Pacific Islander, Native American, and Other. The data analysis was performed using STATA/BE version 18.5. Univariable and multivariable logistic regression models were applied to evaluate the relationship between race and clinical and healthcare utilization outcomes. Results: In 2022, 7479 hospitalizations were recorded for cholangiocarcinoma in the United States. Among these, 65.99% were White, 13.27% Hispanic, and 10.13% African American. There was a statistically significant difference in gender distribution across racial groups (p < 0.001), with males comprising the majority in all groups. Males outnumbered females in all racial groups except among the Hispanic group. Significant racial disparities in mortality were observed, with White patients showing a mortality rate of 6.69%, compared to higher rates among African American (9.76%), Native American (8.51%), and Asian or Pacific Islander (8.09%) patients, while Hispanic (5.04%) and Other (5.88%) groups had lower rates (p < 0.001). Conclusions: The study underscores the racial disparities among cholangiocarcinoma hospitalizations, with African American, Native American, and Asian patients facing disproportionately higher mortality and poorer in-hospital outcomes compared to White patients. This analysis highlights the healthcare strategies and policy reforms to promote equitable treatment by mitigating these disparities and to improve cholangiocarcinoma outcomes. Full article

Trematode infections caused by Fasciolidae and Paramphistomidae remain widespread in livestock, resulting in substantial economic losses. The two distinct fluke families are difficult to distinguish morphologically, and molecular identification provides the most reliable means of accurate diagnosis. In Ecuador, however, molecular data on these parasites are scarce. In this study, we collected trematodes from cattle rumen and bile ducts, molecularly identified them, and assessed their phylogenetic relationship to Fasciola hepatica to determine their introduction pathways into South America. Genomic DNA was extracted, and PCR was used to amplify the ITS2 (~500 bp) and COXI (~266 bp) regions; all amplicons were Sanger-sequenced. Phylogenetic trees for both markers were constructed using a Maximum Likelihood approach with 1000 bootstrap replicates in CIPRES v3.3. The rumen fluke exhibited 99% ITS2 and COXI similarity to an Indian Cotylophoron cotylophorum strain, while the bile-duct fluke showed 99% ITS2 and 100% COXI similarity to F. hepatica isolates from Australia and Nigeria, respectively. Distinct single-nucleotide polymorphisms (SNPs) in the ITS2 chromatograms suggest a diploid genome structure in both trematode species. This is the first report of C. cotylophorum in Ecuador, and its presence may be linked to the late 19th-century introduction of Zebu cattle (Bos taurus indicus) from India. Full article

Background/Objectives: Duodenum-preserving pancreatic head resection (DPPHR) preserves digestive and absorptive functions better than pancreaticoduodenectomy (PD). Zinc is primarily absorbed in the duodenum and proximal jejunum and plays a critical role in nutritional maintenance and pancreatic regeneration. However, no studies have compared the postoperative pancreatic volume and serum zinc levels between DPPHR and PD. Methods: We retrospectively analyzed 41 patients who underwent DPPHR (n = 23) or subtotal stomach-preserving PD (n = 18) for low-grade pancreatic malignancies at our institution. The remnant pancreatic volumes on postoperative day 7 and 1 year were measured via computed tomography. Nutritional parameters, including serum albumin, prognostic nutritional index (PNI), and serum zinc levels, were compared between the groups. Serum zinc levels were evaluated in patients with DPPHR (n = 11) or PD (n = 7). Results: The DPPHR group demonstrated significantly better preservation of remnant pancreatic volume on postoperative day 7 and 1 year compared to the PD group (p = 0.045 and p = 0.041, respectively). Volume maintenance ratios were also significantly higher in the DPPHR group. Serum albumin levels at 1 year postoperatively were significantly better in the DPPHR group, although no significant difference was found in the PNI. Among patients evaluated for serum zinc, the DPPHR group showed significantly higher zinc levels compared to the PD group (80.3 vs. 65.8 μg/dL, p = 0.017). Conclusions: DPPHR preserves remnant pancreatic volume and maintains serum zinc levels better than PD, potentially contributing to improved postoperative nutritional status and quality of life. Further prospective studies with larger cohorts are warranted to validate these findings. Full article

Background: Cholangiocarcinoma (CCA) of the liver is a highly aggressive cancer that arises from malignant cells in the bile ducts. Radical surgery remains the only curative option, but major liver resection carries high perioperative risks. This study investigates the predictive value of preoperative bone mineral density (BMD), measured via CT, for perioperative complications, mortality, and long-term outcomes. Methods: The analysis included 202 patients who underwent curative-intent surgery for intrahepatic cholangiocarcinoma (iCCA; n = 97) or perihilar cholangiocarcinoma (pCCA; n = 105) between 2010 and 2019. Preoperative bone mineral density (BMD) was assessed using computed tomography segmentation at the level of the 12th thoracic vertebra. Osteopenia was defined according to established cutoffs. Results: Osteopenia was highly prevalent in both iCCA (53/97, 54%) and pCCA (54/105, 51%) subcohorts. Patients suffering from osteopenia were significantly older than those without (71.1 [62–76.6] years vs. 61.3 [52.9–69.2] years; p < 0.001). Alteration in BMD did not demonstrate a significant prognostic effect in terms of perioperative morbidity (Mann–Whitney U; comprehensive complication index—CCI: 34 [9–56] vs. 40 [21–72] p = 0.185; iCCA: p = 0.803; pCCA: p = 0.165). The median overall survival in our cohort was 19 [14–25] months. Patients with osteopenia did not exhibit a significantly different overall survival compared to those with normal bone mineral density (log-rank p = 0.234). Conclusions: In contrast to our previous observations in other oncological patient cohorts, osteopenia alone had no significant negative impact on clinical outcomes in our large European cohort of patients undergoing curative-intent surgery for CCA. To validate these findings, further prospective studies are warranted. Full article

Hepatobiliary diseases, which include disorders of the liver, gallbladder, and bile ducts, remain a major global health concern. A significant proportion of deaths worldwide are attributed to hepatic diseases, accounting for 4% of the total global mortality in 2023. Among benign hepatobiliary diseases, metabolic dysfunction-associated steatotic liver disease is the most prevalent liver pathology, with a concerning rise in incidence, while it is recognized as the leading cause of liver transplantation in the United States. However, there is a notable rise over time in cases of autoimmune hepatobiliary disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Meanwhile, hepatocellular carcinoma still remains the most frequently diagnosed hepatobiliary malignancy, constituting the third leading cause of malignancy-related mortality globally. Meanwhile, cholangiocarcinoma and gallbladder cancer are the second and third most common hepatobiliary malignancies, respectively, both exhibiting highly aggressive malignant behavior. Despite the notable advances in biomarkers and the development of therapeutic tools, early diagnosis and monitoring are considered pivotal for the management of the aforementioned pathologies. The development of new non-invasive biomarkers that can effectively identify, monitor these pathologies, and guide their management is considered a necessity. Extracellular vesicles (EVs) constitute nanoparticles with several embedded cargoes, with a significant role in intercellular communication, which are considered promising biomarkers in several diseases, including viral, metabolic, autoimmune, and malignant diseases. In this review, we will shed light on the role of EVs as novel frontiers in hepatobiliary diseases. Full article