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Background: Cholangiocarcinoma (CCA) is a type of cancer that develops in the biliary tract. CCA accounts for 10% of primary hepatic cancers and is characterized by its aggressive nature and poor prognosis. This systematic review and meta-analysis aims to assess the prognostic value of the novel hepatic function assessment measure known as albumin-bilirubin (ALBI) grade in patients with CCA. Method: A comprehensive search was conducted on PubMed, Web of Science, Embase, and Scopus databases until August 11, 2023. Studies examining the prognostic impact of ALBI grade in patients with CCA were included. The prognostic effect was evaluated using hazard ratio (HR) with 95% confidence intervals (CI). The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS). The final meta-analysis was performed using R version 4.3.1. Results: The final meta-analysis included 13 studies with 3,434 patients. In univariate analysis (HR = 1.90, 95% CI: 1.65–2.19, P < 0.01) and multivariate analysis (HR = 1.88, 95% CI: 1.41–2.52, P < 0.01), higher ALBI grade was associated with lower overall survival (OS) in patients with intrahepatic CCA (ICCA). Higher ALBI grade was also correlated with decreased recurrence-free survival (RFS), with an HR of 1.63 (95% CI: 1.36–1.97, P < 0.01). Subgroup analysis of different ALBI grade comparisons showed consistent findings with our pooled data. Conclusion: A high ALBI grade indicates poor OS and RFS in patients with CCA especially intrahepatic type. ALBI should be considered a reliable and clinically useful prognostic indicator. Registration: PROSPERO ID: CRD42022379877 [ABSTRACT FROM AUTHOR]

Aims: Neuroendocrine tumours (NETs) occurring in the extrahepatic biliary system are exceedingly rare. While NETs typically manifest as mass lesions, the occurrence of microscopic neuroendocrine cell proliferation without a distinct mass remains undocumented at this location. This study aims to characterise the clinicopathological features of a series of well‐differentiated neuroendocrine lesions involving the extrahepatic biliary tree, including mass forming NETs and microscopic non‐mass‐forming neuroendocrine cell proliferation, designated neuroendocrine cell micronests (NCMs). Methods and results: Surgical resections of NETs/NCMs involving the extrahepatic bile ducts and gallbladder were identified from electronic pathology databases among seven institutions spanning from January 2011 to September 2023. Clinical and histological findings were recorded. Ten patients (four female, six male: age range = 34–75 years) were included in the study. Histopathological examination revealed visible mass‐forming lesions in four cases (1.6–14.0 cm in size), identified in the gallbladder (n = two) or extrahepatic bile duct (n = two), all diagnosed as well‐differentiated NETs. The remaining six cases revealed incidental non‐mass‐forming NCMs in either the cystic duct (n = two), common bile duct (n = three) or gallbladder (n = one), ranging from < 0.1 to 0.4 cm; four were associated with biliary lithiasis. No evidence of metastasis or recurrence was seen in the follow‐up period (range = 0.1–11.2 years). Conclusions: This study highlights the spectrum of extrahepatic biliary well‐differentiated neuroendocrine lesions, ranging from incidental microscopic NCMs to grossly apparent mass‐forming NETs, potentially requiring different clinical management. Noteworthy is the frequent association of incidental microscopic neuroendocrine cell proliferations with biliary lithiasis, indicating a potential neuroendocrine metaplastic pathogenesis that merits further exploration. [ABSTRACT FROM AUTHOR]

Background: Fasciolopsis buski is a large fluke that parasitises the human small intestine, with its infection in the biliary tract being even rarer. Given its relatively rare occurrence in recent years, the clinical diagnosis of F. buski infections can pose certain challenges. Case demonstration: A 59-year-old male patient with a history of consuming raw pig blood was admitted with recurrent upper abdominal pain for over 10 years. Hepatobiliary and pancreatic magnetic resonance cholangiopancreatography showed stenosis of the lower end of the common bile duct, dilatation of the intrahepatic and extrahepatic bile ducts above, and tortuous strips in the common bile duct, indicating parasitic infection. Histopathological examination further confirmed a diagnosis of parasitic infection with F. buski in the biliary tract. The patient was treated with praziquantel after surgery and did not exhibit recurrence during 6 months of follow-up. Conclusions: Biliary tract infection with F. buski is a rare parasitic disease. This case report discusses an extremely rare case of F. buski infection of the biliary tract caused by consuming raw pig blood. The clinical features, common diagnostic methods, imaging and pathological features, differential diagnosis, treatment, and prognosis of this disease were reviewed to facilitate an improved understanding of this rare condition. [ABSTRACT FROM AUTHOR]

Objectives: Posttraumatic upper gastrointestinal bleeding (UGIB) is a very rare consequence of blunt liver trauma. It can be quite a diagnostic challenge for clinicians, as it can clinically manifest many weeks after the trauma or be scantily symptomatic. Methods: The following article would like to provide an analysis of clinical cases of 13 patients following blunt liver injuries, the main symptoms of which was bleeding into the gastrointestinal tract through the biliary tree. The article is research of the published literature concentrating on the influence of modern diagnostic methods (scintigraphy, USG and CT) on the diagnosis and long-term survival of patients with haemobilia caused by blunt liver trauma. In each patient, the condition was presented with UGIB symptoms following blunt trauma, before initiation of operative treatment or before death. The cases were divided into 2 groups: prior to and after introduction of modern diagnostic procedures, and then compared together. Results: The study indicates that liver damage can cause symptoms of UGIB, even after minor abdominal trauma and with delayed and uncharacteristic symptoms. Conclusions: Modern diagnostic methods, such as ultrasound, scintigraphy and CT, make it easier to identify these injuries and choose appropriate treatment, reducing the risk of death. [ABSTRACT FROM AUTHOR]

Simple Summary: Endoscopic ultrasound (EUS) involves study of the organs surrounding the gastrointestinal tract via use of ultrasound technology during upper endoscopy. In patients with suspected pancreatic cancer, EUS is advised to obtain biopsy for confirmation of diagnosis. With the recent advancements, EUS is now being utilized for certain treatments in pancreatic cancer patients, such as putting in stents to relieve blockage, injecting medicine to decrease pain, placing markers in pancreas for better radiation treatment, and destruction of the cancer cells with heat and local chemotherapy. Pancreatic cancer is associated with high rates of morbidity and mortality. Endoscopic ultrasound (EUS)-guided biopsy has become the standard diagnostic modality per the guidelines. The use of EUS has been growing for providing various treatments in patients with pancreatic cancers: biliary and gallbladder drainage for those with malignant biliary obstruction, gastroenterostomy for malignant gastric outlet obstruction, celiac plexus/ganglia neurolysis for pain control, radiofrequency ablation, placement of fiducial markers, and injection of local chemotherapeutic agents. In this review, we explore the recent clinical studies evaluating the EUS-guided treatments in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Ascariasis is a prevalent intestinal helminthic infection caused by Ascaris lumbricoides, commonly known as roundworm. While the disease may remain asymptomatic when the parasites are confined to the intestinal lumen of the small bowel, symptoms and complications can arise when the helminths invade the biliary tree or pancreatic ducts. In cases of severe infection, a mass of roundworms can lead to intestinal complications, such as bowel obstruction. The morphological identification of Ascaris by multimodality imaging techniques plays a crucial role in the diagnosis, as well as in the monitoring and prevention of complications. [ABSTRACT FROM AUTHOR]

Background: Previously, we reported elevated levels of fucosylated α1-acid glycoprotein (fAGP) in plasma samples from patients with diverse types of cancers. Accordingly, fAGP was assumed to be a potential biomarker for the early detection of cancers. Methods: The fAGP level was retrospectively measured in preoperative plasma samples from 213 patients with either hepatic, biliary tract, or pancreatic cancer and was analyzed together with levels of six existing tumor markers determined as reference standards. Results: When the cutoff value was set at 25.45 U/μg, elevated levels of fAGP were significantly observed in cancer patients. The sensitivity, specificity, and accuracy for the detection of malignancy in these diseases were determined to be 70.79, 51.72, and 68.12, respectively. In contrast, all the tumor markers exhibited low sensitivity and accuracy, even though they commonly had extremely high (≥80%) specificity. Further, a significant number of patients in both early and advanced clinical stages were found to be false negative in these tumor makers but were found to be positive in the fAGP level. A dramatic improvement in the diagnosis by tumor markers in such patients with all clinical stages was found by the determination of the fAGP level. This indicated that fAGP could serve to correct false-negative diagnosis with tumor markers. Conclusions: It is believed that fAGP could be a relevant, unique, and highly sensitive biomarker for early diagnosis of hepatobiliary and pancreatic cancers. [ABSTRACT FROM AUTHOR]

Background: Almost all previous reports on endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) involve malignant distal bile duct strictures. However, the feasibility of EUS-HGS for malignant hilar biliary obstruction (MHBO) remains unclear. Aims: This study aimed to evaluate the efficacy and safety of EUS-HGS for MHBO and identify the risk factors associated with technical failure. Methods: In this multicenter retrospective study, we reviewed consecutive patients who underwent EUS-HGS between April 2017 and March 2023 at five institutions. We assessed the overall feasibility and efficacy of EUS-HGS for MHBO, including the factors associated with technical failure, using multivariable logistic regression analysis. Results: A total of 85 patients were enrolled (mean age, 72 years; 36.4% female). Thirty-six patients (42.3%) had surgically altered anatomy, and 43 (50.6%) underwent biliary stenting by transpapillary or percutaneous biliary drainage before EUS-HGS. The rates of technical success, clinical success, and adverse events were 87.0% (74/85), 76.4% (65/85), and 11.8% (10/85), respectively. Multivariable analysis demonstrated that a bile duct diameter ≤ 4 mm was the only independent risk factor for technical failure (odds ratio, 6.12; 95% confidence interval, 1.02–36.6; P = 0.047). The most common reason for technical failure was cholangiography failure (45.4%), followed by inappropriate guidewire position (36.4%). Conclusions: EUS-HGS is a challenging but promising treatment option for MHBO. Patients with a bile duct diameter ≤ 4 mm or inappropriate guidewire position should be careful as these factors can lead to the technical failure of EUS-HGS for MHBO. [ABSTRACT FROM AUTHOR]

Background: Cholangiography for visualization of the biliary tree during laparoscopic cholecystectomy is an important diagnostic roadmap in the context of suspected choledocholithiasis (CDL). The renewed interest in transcystic laparoscopic common bile duct exploration (LCBDE) necessitates a general description of the range of CDL presentations. Our aim was to establish a novel classification system of intraoperative cholangiograms (IOCs) to advance research efforts in this field. Methods: A novel cholangiogram classification system, featuring 8 distinct presentations of choledocholithiasis, was applied to a data set of 80 preintervention IOCs for suspected choledocholithiasis. The classification system is as follows: A (no common bile duct stones, duodenal filling present, and concern for air bubbles), B (no common bile duct stones, no duodenal filling, and concern for sludge), C1 (stone(s) < 2x size of cystic duct with duodenal filling), C2 (stone(s) < 2x size of cystic duct without duodenal filling), D1 (stone(s) ≥ 2x size of cystic duct with duodenal filling), D2 (stone(s) ≥ 2x size of cystic duct without duodenal filling), E1 (congenital anatomical variant and/or common duct stricture), and E2 (surgically altered biliary anatomy). Results: Cholangiogram review yielded preintervention classifications for 6 of 8 variants (A-E): A (7.5%), B (3.75%), C1 (23.75%), C2 (42.5%), D1 (15%), and D2 (7.5%). Analysis of cystic duct diameter yielded no significant differences among classification groups, indicating no predominant pattern of cystic duct anatomy within a given classification. Discussion: An IOC classification system for suspected choledocholithiasis is foundational to answering key clinical questions for transcystic laparoscopic common bile duct exploration. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (iCCA) has been subclassified by its gross morphology into the mass-forming (MF), periductal-infiltrating (PI), and intraductal growth (IG) types and their combinations. This classification correlates well with clinical features; for example, MF-iCCA has less lymph-node metastasis and a better prognosis than PI-iCCA. According to the recently accumulated evidence from histological investigations, the WHO classification endorsed a subclassification scheme in which iCCA cases are classified into small- and large-duct types. Small-duct iCCA is considered to originate from septal or smaller bile ducts and is characterized by less frequent lymph-node metastasis, a favorable prognosis, and an MF appearance. Large-duct iCCA arises around the second branch of the biliary tree and has more aggressive biology and distinct genetic abnormalities. According to the practice guidelines for iCCA from the Liver Cancer Study Group of Japan and the National Comprehensive Cancer Network, upfront surgery is recommended for iCCA without distant metastasis regardless of the morphological subtype, based on clinical experience. In consideration of the biological heterogeneity of iCCA, the treatment strategy for iCCA needs to be reconsidered based on the WHO subtypes. [ABSTRACT FROM AUTHOR]

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To assess the clinical usefulness of teicoplanin optimized by means of a therapeutic drug monitoring (TDM)-guided approach for treating secondary bloodstream infections (BSIs) caused by Enterococcus faecium. Hospitalized patients having in the period 1 March 2021–31 October 2024 a documented BSI caused by glycopeptide-susceptible Enterococcus faecium being treated with teicoplanin as definitive targeted therapy optimized by means of a real-time TDM-guided expert clinical pharmacological advice (ECPA) program were retrospectively included. Teicoplanin trough concentrations (Cmin) ranging from 20 to 30 mg/L were defined as the desired target of efficacy based on international guidelines. Univariate analysis was performed for assessing variables potentially associated with microbiological failure (defined as persistence at the infection site of the index Enterococcus faecium strain after more than 7 days from starting treatment as documented by follow-up blood cultures). Overall, 67 patients (median age 70 years; male 55.2%) were included. Catheter-related BSIs (50.7%) and intrabdominal/biliary tract (29.9%) infections were the main sources of Enterococcus faecium BSI. The desired target of teicoplanin Cmin was attained in 62.7% of patients at the first TDM assessment and significantly increased to 85.1% (p = 0.003) at subsequent TDM-guided ECPA instances during the overall treatment course. Microbiological eradication was obtained in 95% of cases (63/67). In the univariate analysis, failing effective source control was the only variable associated with an increased risk of microbiological failure (75.0% vs. 12.7%; p = 0.01). Targeted TDM-guided teicoplanin therapy, coupled with effective source control of the primary infection site by granting microbiological eradication in the vast majority of cases, may be considered a reasonable strategy for managing glycopeptide-susceptible Enterococcus faecium secondary BSIs. [ABSTRACT FROM AUTHOR]

Biliary and pancreatic tract stenosis are hallmark symptoms in pancreaticobiliary diseases, transcending malignancy. Endoscopic techniques are pivotal for biliary/pancreatic drainage; however, challenging scenarios arise when attempting to pass a guidewire (GW) through obstruction. Cholangioscopy-assisted GW placement has proven valuable, but challenges persist in its execution, particularly in maneuvering the GW through cholangioscopy. Therefore, we explored the integration of a 3-Fr microcatheter into cholangioscopy with the aim of enhancing direct visualization and offering a super-selective approach. When GW manipulation under a digital single-operator cholangioscope (D-SOC) guidance was still unsuccessful in a resistant obstruction, the 3-Fr microcatheter was introduced. This technique was performed in 42 individuals for 37 biliary and 5 pancreatic duct drainages, among which there were 19 malignant, 18 benign, and 4 anastomotic obstructions. In all patients, contrast-filled cholangiography in the target area couldn't be achieved at the pre-microcatheter insertion stage due to obstruction. The technical success rate was 85.7% overall, 89.5% in malignant strictures, 84.2% in benign strictures, and 75.0% in anastomotic obstructions, resulting in a clinical success rate of 78.6%. The use of a 3-Fr microcatheter appears effective for endoscopic drainage performed for obstruction. This technique could pave the way for improved outcomes in patients with pancreaticobiliary diseases. [ABSTRACT FROM AUTHOR]

Background: Incidentally discovered focal liver lesions (FLLs) are a common reason for referral to hepatobiliary services. These lesions are frequently found in patients with colorectal cancer, cirrhosis, or incidentally during evaluations for abdominal pain or shock. Several established diagnostic tools such as magnetic resonance imaging (MRI), transabdominal ultrasound (US), and computed tomography (CT) are well-studied for assessing liver diseases. Endoscopic ultrasound (EUS), traditionally used for evaluating the mediastinum, biliary tract, esophagus, stomach, and pancreas, is increasingly complementing these traditional diagnostic methods in hepatology. The study aimed to delineate the endoscopic ultrasound elastography role in visualization and hepatic focal hepatic tissue differentiation of lesions in comparison to the routine radiological and laboratory methods. Methods: A cross-sectional study was conducted, we enrolled 41 patients with hepatic focal lesions, abdominal ultrasonography, triphasic CT abdomen, and Endosonography examinations were performed on all participants. Results: There was a highly significant difference between the studied groups as regards the Strain Ratio and Echogenicity (P0.01). Conclusion: Ultrasound elastography and strain ratio are promising, non-invasive, nondependent on any contrast material techniques that could significantly enhance routine grey-scale sonographic examinations of the liver by better delineating the characteristics of hepatic focal lesions. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Measurements Results Conclusion To investigate the prevalence and incidence of dementia in patients with non‐overtly functional adrenal tumours (NOFATs).A national retrospective register‐based study was conducted on patients diagnosed with NOFAT and controls diagnosed between 2005 and 2019, in Sweden. Individuals diagnosed with overt adrenal hormone excess or previous malignancies were excluded. Sensitivity analyses were performed in subgroups with a combination of gallbladder/biliary tract/pancreatic disease. and acute appendicitis, as well as 3‐ and 12‐months of malignancy‐free survival.Prevalence and incidence of dementia. The secondary outcomes were Alzheimer's disease and vascular dementia.Among 20,390 cases, 12,120 (59.4%) were women, and the median (IQR) age was 66 (57–73) years. Among the 125,392 controls, 69,994 (55.8%) were women and the median (IQR) age was 66 (57–73) years. Patients with NOFATs had a lower prevalence of dementia compared to controls (odds ratio [OR] 0.58, 95% CI 0.50–0.68, adjusted OR [aOR] 0.47, 95% CI 0.40–0.56). During the follow‐up period (median 4.9 years, IQR 2.2–8.2), incidence of dementia was similar in NOFATs and controls (hazard ratio [HR] 1.05, 95% CI 0.97–1.15, adjusted HR [aHR] 1.06, 95% CI 0.97–1.15). Similar results obtained for Alzheimer's dementia (aOR 0.44, 95% CI 0.34–0.57; aHR 0.94, 95% CI 0.80–1.10) and vascular dementia (OR 0.71, 95% CI 0.52–0.94, aOR 0.48, 95% CI 0.35–0.64; HR 1.29, 95% CI 1.08–1.53, aHR 1.13, 95% CI 0.95–1.35) as well as in the sensitivity analyses. Adrenalectomy did not change the results.NOFAT was not associated with an increased risk of dementia. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the psychological distress and its influencing factors in patients with biliary tract malignant tumors, alongside the development of a predictive model. Methods: A total of 219 patients diagnosed with biliary tract malignant tumors who were admitted to the Department of Liver Surgery at Fudan University Shanghai Cancer Center from July 2021 to May 2023, were selected using a convenience sampling method. Research tools involve psychological distress management screening tools, a demographic questionnaire, self-rating anxiety and depression scales, and the Chinese version of the Memorial Symptom Assessment Scale. Bootstrap method was utilized for repeated sampling to identify relevant factors influencing psychological distress in biliary tract cancer patients. The R software was employed to create a nomogram model, and the model's accuracy and predictive performance were assessed using the receiver operating characteristic curve (ROC) and the Hosmer-Lemeshow test. Results: The average score of psychological distress among the 219 patients was (3.91 ± 2.44), with a psychological distress detection rate of 54.8%. Regression model results indicated that factors such as the presence of distant metastasis, comorbidity with other major diseases, poor sleep quality, anxiety, and severity of anxiety and depression were the primary influencers of psychological distress. Conclusion: The detection rate of psychological distress in patients with biliary tract malignant tumors is notably high. The predictive model constructed in this study exhibits good predictive efficacy and clinical value, providing valuable reference for healthcare professionals in developing targeted intervention strategies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the feasibility and performance of 5.0 T MRI in MR Cholangiopancreatography (MRCP) imaging compared to 3.0 T, focusing on detail visualization, signal-to-noise ratio (SNR), and image artifacts. Methods: A prospective study from May to October 2023 involved 20 healthy subjects and 19 with biliary dilation. Both groups underwent MRCP using 3.0 T and 5.0 T scanners. The detail visualization capability of the biliary tree and the SNR of the images were quantitatively evaluated. Two experienced MRI diagnostic physicians assessed the image artifacts qualitatively on a scale of 1 to 5. The t-test or Wilcoxon signed-rank test compared the quantitative results of biliary visualization and SNR between 3.0 T and 5.0 T scanners, while the Wilcoxon signed-rank test was used for comparing the level of image artifacts between the two scanners. The inter reader consistency was tested using Kappa test. Results: In both healthy subjects and those with biliary dilation, the 5.0 T group exhibited significantly higher numbers of biliary tree branches, along with greater total and maximum branch lengths, compared to the 3.0 T group (P<0.05). Although the maximum branch length was higher in the 5.0 T group among healthy subjects, this difference was not statistically significant (P = 0.053). No notable differences were observed in SNR and image artifact levels between the two groups across both field strengths (P>0.05). Conclusions: MRCP at 5.0 T offers superior biliary tree visualization compared to 3.0 T. The performance regarding SNR and image artifacts between the two is relatively comparable. [ABSTRACT FROM AUTHOR]

The genus Enterococcus is increasingly recognized for its involvement in various human infections, with several species known to be pathogenic. This study characterized Enterococcus sp. SMC-9, isolated from bile of a patient with cholangitis, and compared its characteristics with those of Enterococcus montenegrensis CoE-012-22T, recently isolated from dried beef sausage. A comprehensive analysis, encompassing phylogenetic, genomic, and phenotypic studies, confirmed that strain SMC-9 belongs to the same species as E. montenegrensis CoE-012-22T. However, comparative genomic analysis revealed key differences in virulence and antibiotic resistance gene profiles between the two strains. Notably, genes related to exopolysaccharide biosynthesis and the L-rhamnose biosynthesis pathway were found exclusively in strain SMC-9, suggesting their role in the strain's colonization of the biliary tract and its involvement in cholangitis. Additionally, the tetracycline resistance gene tet(M), which was absent in E. montenegrensis CoE-012-22T, was identified in strain SMC-9, explaining its high tetracycline minimum inhibitory concentration (>16 μg/mL). These findings highlight the unique pathogenic traits of strain SMC-9 compared to E. montenegrensis CoE-012-22T. Our study underscores the significant genetic and phenotypic variations that can exist among strains within the same species, highlighting the critical need for strain typing to assess their potential impact on patient outcomes and public health. [ABSTRACT FROM AUTHOR]

Background: In patients with pancreaticobiliary maljunction complicated by congenital biliary dilatation, the pancreatic enzyme flows back into the bile, leading to bile duct carcinogenesis. Although the biliary tract resection and reconstruction is well documented to decrease the rate of malignancy, cancer occurrence has been reported in the residual intrahepatic or intrapancreatic bile duct, even after resection. We report a case of multiple biliary tract cancers in the liver complicated by congenital biliary dilatation, whose tumor lesions were resected en bloc without disconnecting the biliary tract by simultaneous pancreatoduodenectomy and living donor liver transplantation. Case presentation: A 27-year-old woman presented with epigastric discomfort. Examination indicated multiple biliary tract cancers complicated by congenital biliary dilatation. Computed tomography scan revealed three papillary tumors in the right hepatic duct with increased 18F-FDG accumulation on positron emission tomography. Contrast-enhanced ultrasound revealed another lesion in the left hepatic duct. Adenocarcinoma cells were detected using bile and choledochal brush cytology. Tumors resection by right lobectomy or trisegmentectomy of the liver and extrahepatic bile duct resection indicated a high risk of postoperative liver failure; the residual liver volumes were calculated only 277 ml or 176 ml, respectively. In addition, tumor recurrence owing to bile leakage during the surgery and carcinogenesis from the remaining bile duct were concerned. Pancreatoduodenectomy was performed without disconnecting the biliary tract, and the tumors were resected en bloc with the whole liver. The left lobe liver graft from the husband was then transplanted. After 5 years of adjuvant treatment with tegafur/gimeracil/oteracil potassium, she remained in remission eight and half years after the surgery. Conclusions: Given the mechanism and development of cancer in the congenital biliary dilatation, simultaneous pancreatoduodenectomy and liver transplantation may be considered, especially in the case of young patients. [ABSTRACT FROM AUTHOR]

The article discusses the application of machine learning (ML) to histology for studying cholangiopathies, focusing on the development of a platform called BiliQML. BiliQML enables high-resolution phenotyping of biliary forms through the use of cholangiocyte scans obtained by immunostaining with anti-Keratin-19. The study demonstrates the potential of ML-based approaches in standardizing histological analysis and deepening the understanding of liver pathology, offering a unique opportunity to enhance diagnostic accuracy and research in the field of cholangiopathies. [Extracted from the article]

Background: Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis. Methods: Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023. Results: Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve. Conclusions: Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis. [ABSTRACT FROM AUTHOR]

Simple Summary: The environment of cancer cells, made up of multiple cell types, macromolecules, and signaling molecules, displays numerous properties that promote cancerous diseases. This tumor microenvironment is characterized by a high degree of diversity, offering a substantial number of specific markers that can be exploited to target tumor processes, both for diagnosis and therapy. The fibroblast activation protein, overexpressed on the surface of cancer-associated fibroblasts, has attracted considerable interest through the design of inhibitors, used as radiolabeled molecular imaging probes in nuclear medicine. Some of these experimental radiopharmaceuticals have already been extensively studied in clinical settings, notably for cancer imaging when other molecular imaging techniques present limitations. Despite this, innovative analogs continue to be developed, some of which for both diagnostic and therapeutic applications. The tumor microenvironment (TME) is a dynamic and complex medium that plays a central role in cancer progression, metastasis, and treatment resistance. Among the key elements of the TME, cancer-associated fibroblasts (CAFs) are particularly important for their ability to remodel the extracellular matrix, promote angiogenesis, and suppress anti-tumor immune responses. Fibroblast activation protein (FAP), predominantly expressed by CAFs, has emerged as a promising target in both cancer diagnostics and therapeutics. In nuclear medicine, targeting FAP offers new opportunities for non-invasive imaging using radiolabeled fibroblast activation protein inhibitors (FAPIs). These FAP-specific radiotracers have demonstrated excellent tumor detection properties compared to traditional radiopharmaceuticals such as [18F]FDG, especially in cancers with low metabolic activity, like liver and biliary tract tumors. The most recent FAPI derivatives not only enhance the accuracy of positron emission tomography (PET) imaging but also hold potential for theranostic applications by delivering targeted radionuclide therapies. This review examines the biological underpinnings of FAP in the TME, the design of FAPI-based imaging agents, and their evolving role in cancer diagnostics, highlighting the potential of FAP as a target for precision oncology. [ABSTRACT FROM AUTHOR]

Background and Clinical Significance: Biliary tract injuries are a recognized complication of laparoscopic cholecystectomy. Early diagnosis and prompt management are crucial to minimize complications such as bile leaks, strictures, and fistula formation. This case report highlights the use of a biodegradable biliary stent in managing a complex biliary injury and discusses the impact of delayed diagnosis on treatment outcomes. Case Presentation: We present the case of a 30-year-old male who sustained a Strasberg E2 biliary tract injury during a laparoscopic cholecystectomy. Initially misdiagnosed, the injury was only recognized on the fourth postoperative day. The patient underwent a Roux-en-Y hepaticojejunostomy and subsequently developed a postoperative biliary fistula, which was managed with percutaneous drainage. A biodegradable biliary stent was later placed to address a stricture and minimize the need for future interventions. One year later, the patient presented with symptoms of cholangitis, and radiological findings revealed a narrowing of the biliary lumen. The stricture was resolved and an endoscopic gastrojejunal shunt was placed to prevent further complications. The patient is currently in good condition with no signs of further complications. Conclusions: This case emphasizes the importance of early diagnosis in managing biliary tract injuries and highlights the potential of biodegradable stents to reduce the need for repeat interventions. Despite a delayed diagnosis necessitating complex surgical procedures, the use of a biodegradable stent proved effective in managing postoperative complications. Further studies are needed to evaluate the long-term efficacy of biodegradable stents in similar clinical scenarios. [ABSTRACT FROM AUTHOR]

Introduction: Knowledge of anatomical variants that affect the hepatic duct (HD) are of particular clinical relevance during hepatobiliary surgical procedures. More specifically, the aberrant anatomy of the common HD is the most common anatomical variation affecting the biliary tree. Below, we describe different classifications of anatomical variants that affect this canal. According to Huang's classification, variations are determined depending on the insertion of the right posterior hepatic duct (RPHD). Materials and methods: Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases were investigated until January 2024. The methodological quality was assessed with an anatomical studies assurance tool (AQUA). Pooled prevalence was estimated using a random effects model. For the subgroup analysis, Student's T-test was used. Results: The prevalence rate of aberrant hepatic duct (AHD) was 15% (confidence interval [CI] of 7–22%). The first subgroup had cadavers and images. For the cadavers, the prevalence was 15.83% (CI: 11.22–18.3%), while the images had a prevalence of 22.06% (CI: 18.12–25.33%). This subgroup analysis showed no statistically significant difference between these groups (p = 0.127). The second subgroup comprised the continents where the included studies were from. In this subgroup, no statistically significant differences were found (p = 0.613). Finally, regarding the right or left laterality of the HD variant, there were no statistically significant differences (p = 0.089). Conclusion: A AHD corresponds to a finding that can occur in a significant percentage of our society, which could be an accidental discovery during surgeries or present asymptomatically throughout life and be a cadaveric discovery later. We believe it is important for surgeons to have prior knowledge of the possible variants of HD to prevent possible complications during and after surgery. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Choledochal cysts are congenital cystic dilatation of any section of the bile ducts. They have been divided into 5 primary categories. This is the case of an intrahepatic variant of bile duct cysts originating from the main lobar bile ducts at the confluence, initially radiologically identified as biliary cystadenoma in segments 4b and 5. Case Report: A 35-year-old woman presented with right upper quadrant pain and palpable mass during examination. History and laboratory results were normal. Magnetic resonance cholangiopancreatography revealed a complicated cystic lesion compressing right and left proximal hepatic ducts, diagnosed radiologically as biliary cyst adenoma in segments 4b and 5. Intraoperatively, large cyst found in liver segment 4b and 5, extending infra-hepatic, included the confluence of the common hepatic duct and extended to the gallbladder. It was easily separable from the gallbladder, and total cholecystectomy was done; however, the cyst was inseparable from the confluence of common hepatic duct. The peritoneum over the cyst, containing the right and left hepatic duct and in the area of confluence, was dissected and pushed down to avoid injury; enucleation of the lower border was successfully done. Upper border was transected through liver parenchyma; many small ductules connected with the cyst were ligated. Resection should be done to decrease possibility of malignant transformation and prevent recurrent cholangitis. Conclusions: Class VII choledochal cyst is rare, and surgery is the preferred choice, after proper evaluation of the cyst and surrounding structure. Magnetic resonance cholangiopancreatography still has a high overall accuracy for choledochal cyst diagnosis and classification. [ABSTRACT FROM AUTHOR]

Mixed cholangiocarcinoma is a rare and aggressive neoplastic proliferation of biliary tract epithelial cells, accounting for up to 20% of primary liver cancers. It is the second most common primary liver malignancy with a 5-year survivability of less than 10% at diagnosis and is associated with various inflammatory diseases. Current management involves systemic chemotherapy, targeted radiation, and surgical resection, but long-term survival remains low, especially for surgically unresectable cases. Novel discoveries and understandings of the tumor microenvironment reveal new opportunities for targeted therapies for cholangiocarcinoma. Specifically, new pharmaceuticals including cell-based vaccines, tumor-associated neutrophils, and hepatic stellate cells may make good therapeutic targets. Tumor-reactive stroma and cancer-associated fibroblasts are also heavily implicated in disease progression. This comprehensive review aims to discuss emerging pharmaceutical therapies for targeting the cholangiocarcinoma microenvironment and chemokine pathways involved in the pathogenesis of cholangiocarcinoma followed by a risk-benefit analysis of proposed pharmaceutical therapies for treatment. A literature search on PubMed, Google Scholar, and PMC was done including the terms cholangiocarcinoma, targeted therapies, chemokine pathways, microenvironment, therapeutic targets, chemotherapy, and immune cell, alone or in combination. The articles in the English language and published in the last 10–15 years were selected to discuss in this review article. Selective therapies targeting tumor microenvironment can be fruitful in inducing tumor apoptosis and suppressing cholangiocarcinoma proliferation. Immunosuppressive therapies and immune checkpoint inhibitors also demonstrate promise in improving patient outcomes, specifically in patient's intolerance to chemotherapy. [ABSTRACT FROM AUTHOR]

Biliary tract tumors (BTC) account for about 3% of all digestive system tumors, with rising incidence and limited treatment options, particularly for advanced stages, underscoring the need for innovative therapies. This retrospective cohort study evaluated the safety and efficacy of a novel regimen combining hepatic artery infusion chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-HAIC) alongside lenvatinib and programmed cell death protein-1 (PD-1) inhibitors (mFOLFOX-HAIC+lenvatinib+PD-1i) compared to standard regimens of gemcitabine plus cisplatin, gemcitabine plus S1, or gemcitabine plus oxaliplatin (GC/GS/GEMOX) in advanced BTC patients treated from March 2019 to November 2023. A total of 89 patients were analyzed, with 55 receiving hepatic arterial infusion chemotherapy and 34 receiving the GC/GS/GEMOX regimens. Among these, 23 patients were in the mFOLFOX-HAIC+lenvatinib+PD-1i group, while 24 were in the GC/GS/GEMOX group. The median progression-free survival (mPFS) for the mFOLFOX-HAIC+lenvatinib+PD-1i group was 15 months compared to 6 months for the GC/GS/ GEMOX group. Similarly, the median overall survival (mOS) was 20 months for the mFOLFOXHAIC+ lenvatinib+PD-1i group versus 13 months for the GC/GS/GEMOX group. The objective response rate (ORR) and disease control rate (DCR) for the mFOLFOX-HAIC+lenvatinib+PD-1i group were 48.5% and 87.0%, respectively, both significantly higher than those observed in the GC/ GS/GEMOX group at three months of treatment. The incidence of adverse events (AEs) was similar between the mFOLFOX-HAIC+lenvatinib+PD-1i group and the GC/GS/GEMOX group, at 86.5% and 84.2%, respectively, with no statistically significant difference in complication rates. Overall, mFOLFOX-HAIC+lenvatinib+PD-1i appears to be a safe and well-tolerated treatment for advanced BTC, demonstrating superior mPFS and mOS compared to standard regimens. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is a hepatobiliary malignancy which can manifest anywhere along the biliary tree. Intrahepatic cholangiocarcinoma occurs in the liver within or beyond the second order bile ducts. The prognosis for patients with intrahepatic cholangiocarcinoma is poor, even when successfully resected there is a very high rate of local recurrence. The available systemic therapies are currently limited and have high rates of toxicity. Percutaneous and transarterial liver-directed therapies can be used to treat intrahepatic cholangiocarcinoma with results comparable to current standard of care systemic therapies in some circumstances. This manuscript will review these the techniques and efficacy of percutaneous and transarterial liver-directed therapies for intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Thermal ablation is used to treat liver metastasis including those from breast cancer. The ablation is associated with pain, hemorrhage, and biliary structure damage leading to bilomas. Biloma is a collection of bile that can occur inside or outside the biliary system, which could happen as a rare complication of surgery (from procedures like abdominal surgery or diagnostic procedures), trauma, or spontaneously. We report a case of biloma development after microwave ablation (MWA) of a metastatic lesion in the liver. We present a 66-year-old female diagnosed with stage 4 intraductal carcinoma of the right breast with metastasis to the liver. She developed biloma and infarction of the left lobe of the liver following MWA, which was treated with percutaneous internal/external biliary drain placement. Her symptoms and liver function tests were completely resolved after 3 months, and her left hepatic lobe completely atrophied in the same period. Biloma is a rare but concerning complication of MWA, therefore high suspicion should be maintained in patients presenting with cholestatic symptoms and fever postprocedure. When identified, drainage with antibiotic therapy can effectively treat biloma and resolve the symptoms.

Background/Aims Hepatobiliary scintigraphy (HBS) is used to evaluate bile excretion. This study aimed to evaluate biliary excretion during endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using HBS. Methods We retrospectively evaluated 78 consecutive patients with malignant extrahepatic biliary obstruction, who underwent HBS after EUS-HGS between April 2015 and July 2022. The peak time and decay rate were scored with 0, 1, or 2 points based on thresholds of 20 and 35 minutes, and 10% and 50%, respectively. A total score of 4 or 3 was considered indicative of good bile excretion, whereas scores of 2, 1, or 0 indicated poor bile excretion. Results The good and poor bile excretion groups included 40 and 38 cases, respectively. The group with good bile excretion had a significantly longer time to recurrent biliary obstruction compared to the poor bile excretion group (not reached vs. 124 days, p=0.026). Multivariate analysis identified the site of obstruction as a significant factor influencing good bile excretion (odds ratio, 3.39; 95% confidence interval, 1.01–11.4, p=0.049), with superior bile excretion observed in cases involving upper biliary obstruction compared to middle or lower biliary obstruction. Conclusions In patients with malignant biliary obstruction who underwent HGS, the site of obstruction is significantly associated with stent patency.

Congenital anomalies of the biliary tree are rare and present challenges for endoscopists performing interventions such as endoscopic retrograde cholangiopancreatography (ERCP). The reported incidence of ectopic biliary drainage ranges from 2% to 20%, and the condition is often associated with pancreatobiliary complications, including choledocholithiasis (56%), cholangitis (39%), and acute pancreatitis (18.2%). These developmental abnormalities originate during embryogenesis. Uncommon sites for the ampullary opening include the third or fourth part of the duodenum, the stomach, and the pancreatic duct. We report a rare case of ectopic ampulla opening into the pylorus, which presented with cholangitis and was successfully managed with a modified ERCP technique.

Obtaining diagnostic-quality magnetic resonance imaging (MRI) of the abdomen in critically ill patients can be difficult due to challenges with breath-holding and the inability to follow technologist instructions. Protocols that harness advances in commercially available MRI techniques provide a potential solution, particularly using the golden radial angle sparse parallel (GRASP) technique for dynamic post-contrast T1-weighted imaging. The GRASP technique uses a combination of free-breathing, a stack-of-stars radial acquisition, and compressed sensing reconstruction acquired over several minutes to produce motion-free images at time points defined by the user; these include the non-contrast, arterial, venous, and delayed images, which are typical of abdominal MRI protocols. The three cases discussed herein illustrate the use of this technique in providing both exquisite image quality and diagnostic value in the care of critically ill patients with hepatopancreaticobiliary diseases. Our work aims to raise awareness of this technique and its utility in imaging patients who cannot hold their breath for dynamic T1-weighted post-contrast imaging.

Background/Aims Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is performed globally, the procedure remains challenging. Guidewire manipulation is the most difficult step, and there are few reports on the factors associated with unsuccessful guidewire manipulation. This study aimed to assess the significance of the puncture angle on EUS images and identify the most effective guidewire rescue method for patients with unsuccessful guidewire manipulation. Methods We retrospectively enrolled 115 patients who underwent EUS-HGS between May 2016 and April 2022 at two centers. The puncture angle between the needle and the intrahepatic bile duct was measured through EUS movie records. Results Guidewire manipulation was unsuccessful in 28 patients. Receiver operating characteristic (ROC) curves identified an optimal puncture angle cutoff value of 85° (cutoff value, 85°; area under the ROC curve, 0.826; sensitivity, 85.7%; specificity, 81.6%). Multivariate analysis demonstrated that a puncture angle

[Display omitted] Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population. [ABSTRACT FROM AUTHOR]

Fibrolamellar carcinoma (FLC) is a rare but fatal cancer that occurs primarily in young people. There are currently no known effective treatments, although several promising treatments appear to be in development. Genetic studies have confirmed that almost all FLC tumors have a fusion protein marker (DNAJB1-PRKACA) encoded by a fusion gene (DNAJB1-PRKACA); It is currently accepted as a diagnostic criterion for FLCs. Several research teams have established patient-derived xenograft (PDX) FLC models using immunocompromised animals as hosts and patient tissue samples (tumors or ascites) as primary sources for PDX-derived organoids. These FLC organoids are composed of FLC epithelia, endothelial progenitor cells, and stellate cells. CRISPR/Cas9 was used as a gene editing technique to modify mature hepatocytes to obtain ex vivo FLC-like cells expressing the fusion gene and/or other mutated genes associated with FLCs. Although these models simulate some but not all FLC features. Drug screening using these models has not proven effective in identifying clinically useful treatments. Genetic studies comparing FLCs to normal maturing endodermal cell lineages have shown that FLCs share genetic signatures not with hepatocytes, but with subpopulations of biliary tree stem cells (BTSCs), hepato/pancreatic stem/progenitor cells that consistently reside in peribiliary glands (PBGs) located in the biliary tree and are sources of stem cells for the formation and postnatal regeneration of the liver and pancreas. Therefore, it is expected that models of BTSCs, instead of hepatocytes may prove more useful. In this review, we summarize the status of the various FLC models and their features, applications, and limitations. They provide opportunities to understand the cause and characteristics of this deadly disease and are models from which effective treatments can be identified. [ABSTRACT FROM AUTHOR]

Simple Summary: In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia–PCP alignment, whereas the hepatocyte–sinusoid alignment composes hepatic lobules. High-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm (IPNB), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of biliary tract carcinoma (BTC). All cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while BTC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma. Some BTC replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of vascular supply in BTC and its precursors. There are several types of microvasculature supplying neoplasms: "newly formed blood vessels" (neoangiogenesis), which are a component of the tumor microenvironment (TME) of invasive carcinoma with wound healing-like reaction; and "pre-existing blood vessels", which are used as tumor-supplying vessels by neoplasms (co-option vessels) and are likely to develop in hypervascularized organs. We herein review the microvasculature of neoplasms of biliary tract with reference to pre-existing vessels and vessel co-options. In the hepatobiliary system, intrahepatic large and extrahepatic bile ducts (large bile ducts) and the gallbladder as well as hepatic lobules are highly vascularized regions. In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia–PCP alignment, whereas the hepatocyte–sinusoid alignment composes hepatic lobules. Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are the main biliary tract carcinomas. CCA is subdivided into distal (d/CCA), perihilar (pCCA), and intrahepatic (iCCA), and iCCA is subdivided into small duct type (SD-iCCA) and large duct type (LD-iCCA). High-grade biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of LD-iCCA, p/dCCA, and GBC. In the large bile ducts and gallbladder, all cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while p/dCCA, LD-iCCA, and GBC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma, a unique microvasculature different from that of co-option or neoangiogenesis. Regarding iCCA showing invasion into the hepatic lobules, some SD-iCCAs replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of malignant progression and of vascular supply in CCAs and its precursors. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs) are transmembrane proteins permeable to water and a series of small solutes. AQPs play a key role in pathways of hepatobiliary secretion at the level of the liver, bile ducts, and gallbladder. AQP8 and -9 are pivotal in facilitating the osmotic water movement of hepatic bile, which is composed of 95% water. In the biliary tract, AQP1 and -4 are involved in the rearrangement of bile composition by mechanisms of reabsorption/secretion of water. In the gallbladder, AQP1 and -8 are also involved in trans-epithelial bidirectional water flow with the ultimate goal of bile concentration. Pathophysiologically, AQPs have been indicated as players in several hepatobiliary disorders, including cholestatic diseases and cholesterol cholelithiasis. Research on AQP function and the modulation of AQP expression is in progress, with the identification of potent and homolog-specific compounds modulating the expression or inhibiting these membrane channels with promising pharmacological developments. This review summarizes the contribution of AQPs in physiological and pathophysiological stages related to hepatobiliary function. [ABSTRACT FROM AUTHOR]

Cholangiopathies are poorly understood disorders with no effective therapy. The extrahepatic biliary tree phenotype is less studied compared to the intrahepatic biliary injury in both human disease and Mdr2−/− mice, the established cholestatic mouse model. This study aimed to characterize the extra hepatic biliary tree of Mdr2−/− mice at various ages and to determine if injury can be repaired with the antioxidant and glutathione precursor N-acetyl-L-Cysteine treatment (NAC). We characterized extra hepatic bile ducts (EHBD)s at various ages from 2 to 40 weeks old FVB/N and Mdr2−/− mice. We examined the therapeutic potential of local NAC ex vivo using EHBD explants at early and late stages of injury; and systematic therapy by in vivo oral administration for 3 weeks. EHBD and liver sections were assessed by histology and immunofluorescent stains. Serum liver enzyme activities were analyzed, and liver spatial protein expression analysis was performed. Mdr2−/− mice developed progressive EHBD injury, similar to extrahepatic PSC. NAC treatment of ex vivo EHBD explants led to improved duct morphology. In vivo, oral administration of NAC improved liver fibrosis, and decreased liver enzyme activities. Spatial protein analysis revealed cell-type specific differential response to NAC, collectively indicating a transition from pro-apoptotic into proliferative state. NAC treatment should be further investigated as a potential therapeutic option for human cholangiopathies. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers. Methods: Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts. Results: There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes. Conclusions: We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers. [ABSTRACT FROM AUTHOR]

Background: Numerous recent studies have explored the association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and the risk of various extrahepatic cancers. However, the conclusions were inconclusive. The aim of this study was to clarify this relationship by conducting a robust meta‐analysis. Methods: Systematic searches were conducted on PubMed, Embase and Web of Science databases to identify relevant cohort studies published prior to February 2024. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were combined using a random‐effects model in this meta‐analysis. Results: Eighteen cohort studies (approximately 16.7 million participants) were finally included in this meta‐analysis. MASLD was linked to a higher risk of extrahepatic cancers, such as gastric (n = 10, HR = 1.47, 95% CI: 1.07–2.01), colorectal (n = 13, HR = 1.33, 95% CI: 1.16–1.53), pancreatic (n = 8, HR = 1.41, 95% CI: 1.11–1.79), biliary tract (n = 5, HR = 1.27, 95% CI: 1.18–1.37), thyroid (n = 6, HR = 1.46, 95% CI: 1.02–2.09), urinary system (n = 10, HR = 1.45, 95% CI: 1.25–1.69), breast (n = 11, HR = 1.17, 95% CI: 1.08–1.26) and female genital organ cancers (n = 10, HR = 1.36, 95% CI: 1.11–1.66). However, there was no statistically significant association between MASLD and the risk of head and neck (n = 6, HR = 1.03, 95% CI: 99–1.07), oesophageal (n = 9, HR = 1.26, 95% CI: 0.86–1.86), lung (n = 9, HR = 1.01, 95% CI: 0.92–1.10), prostate (n = 9, HR = 1.06, 95% CI: 0.94–1.19) or small intestine cancer (n = 2, HR = 1.75, 95% CI: 1.00–3.06). Conclusions: This latest large‐scale meta‐analysis indicated that MASLD was associated with an increased risk of various extrahepatic cancers, such as gastric, colorectal, pancreatic, biliary duct, thyroid, urinary system, breast, skin and female genital cancers. Further research is needed to investigate the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Background: The frequency of major cancer surgery in the elderly (≥80 years) has increased concomitantly with the rise in average age of the population. We assessed early postoperative mortality following hepato-pancreato-biliary (HPB) and gastrointestinal (GI) procedures for common malignancies stratified by age. Methods: The National Cancer Database (2004-2017) was queried for patients who underwent resection for GI (gastroesophageal and colorectal) or HPB (pancreatic adenocarcinoma, biliary tract, and primary liver) cancers. We compared early postoperative mortality (30 d and 90 d) stratified by age (65-79 vs ≥80 years) and procedure, and compared survival outcomes by age and operative vs nonoperative management. Results: A total of 709,358 patients were included. The 30-day mortality ranged from 1.8% to 5.8% among patients 65-79 years and from 3.2% to 12.4% among patients ≥80 years depending on procedure. The 90-day mortality ranged from 3.6% to 10.6% in patients 65-79 years compared to 8.4%-21.0% among patients ≥80 years. The overall 90-day mortality was 5.2% for patients 65-79 years and 12.0% for patients ≥80 years (P < .001). Age ≥80 was associated with worse survival among operatively managed patients with each upper GI, HPB, and lower GI malignancy relative to younger patients on multivariable analysis. However, operative management of patients ≥80 years was associated with improved survival relative to nonoperative management. Discussion: Elderly patients suffer higher postoperative mortality after major GI and HPB cancer surgery, but operative management is associated with improved survival among patients ≥80 years as compared to nonoperative management. These data are important to contextualize when counseling elderly patients on their treatment options for localized GI and HPB cancers. [ABSTRACT FROM AUTHOR]

Background: Secondary or metastatic tumors of the pancreas are exceedingly rare. This study aims to elucidate an uncommon etiology contributing to pancreatic masses: extramedullary plasmacytoma. Case Report: A 77-year-old male patient, undergoing treatment for multiple myeloma, presented with jaundice and abdominal pain. Laboratory findings indicated cholestasis. Imaging techniques revealed a dilated biliary tree and a hypoechoic mass in the head of the pancreas. Endoscopic examination showed significant narrowing of the duodenal lumen with an infiltrative pattern in the duodenal wall. Biopsies were taken from the narrowed area, and percutaneous biliary drainage was performed in the radiology department. Histopathological analysis of the biopsies revealed features consistent with plasmacytoma, characterized by infiltration with atypical plasma cells and positivity for CD138 in immunohistochemistry. Conclusion: In cases where a patient with multiple myeloma presents with a pancreatic mass, it is imperative to consider the possibility of a pancreatic plasmacytoma as a potential diagnosis. [ABSTRACT FROM AUTHOR]

Introduction. Biliary complications after orthotopic liver transplantation are the most important and frequent complications, directly related to mortality, graft dysfunction and increased hospital stay. Objective: The objective of this study is to characterize patients who presented biliary complications after liver transplantation, understanding that it is an entity with high morbidity and mortality, with early detection, clinical suspicion and treatment being crucial. Materials and Method. Cross-sectional, retrospective and observational study, with follow-up of 82 patients undergoing liver transplant at the Cardiovascular Foundation between 2013 and 2023, selecting those who presented post-surgical biliary complications. The type of complication, risk factors and postsurgical outcomes were evaluated. Results. There was a predominance of the male sex 59,76% (n = 49) in all transplant patients, the main indication being alcoholism (21,95%). A total of 28 patients presented complications of the biliary tree. The main complication was 50% anastomotic stenosis. Conclusion. Biliary complications are an entity related to morbidity, however, they generally have fewer fatal outcomes in relation to vascular complications. Suspicion and diagnosis with respective intervention are important. [ABSTRACT FROM AUTHOR]

Key Clinical Message: It is important to consider the diagnosis of Sump syndrome in patients with a history of open cholecystectomy, particularly in those who migrate from developing countries where alternative biliary interventions may be limited. The presentation may range from acute severe, mimicking acute ascending cholangitis, to chronic recurrent abdominal pain without evidence of inflammation. Management is a case‐by‐case decision, with principal management aims to decompress the biliary tract and address any underlying sepsis. Sump syndrome is a rare and often long‐term complication of choledochoduodenostomy (CDD). The presentation and severity are variable, and management should be tailored to each patient based on several factors. Herein, we report three cases of sump syndrome, each demonstrating unique diagnostic dilemmas and therapeutic modalities. Case I describes a woman presenting with acute cholangitis, managed with percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP). Case II illustrates a similar presentation complicated by myocardial infarction, necessitating urgent biliary decompression via PTC and subsequent unsuccessful endoscopic stenting. Case III highlights the diagnostic difficulty in a stable patient with inconclusive diagnostic imaging. This case series emphasizes the importance of considering sump syndrome diagnosis in patients with a history of CDD or open cholecystectomy, especially in elderly patients and those who come from regions where alternative biliary interventions may be limited. [ABSTRACT FROM AUTHOR]

Background: In recent years, Raoultella spp. have attracted clinical attention as a new type of pathogen. The most common of human infection with Raoultella are bacteremia, urinary tract infections, abdominal infections, etc. Abdominal infection is a serious and complex infection problem. However, there have been no systematic reports of abdominal infections caused by Raoultella. The objective of this study was to explore the clinical characteristics of Raoultella abdominal infections and provide a reference for clinical practice. Methods: A review of publications on abdominal infections caused by the genus Raoultella between 2009 and 2024 is carried out. This review studied seven parameters: infection type, number of cases, gender, age, comorbidities, treatment, and outcome, and descriptive statistical methods were used to analyze the results. Results: A total of 40 cases (16 Raoultella ornithinolytica and 24 Raoultella planticola) were analyzed: 20 cases of biliary tract infection, 5 cases of liver infection, and 4 cases of peritonitis. Fever and abdominal pain were the main symptoms, and some patients present with multiple skin flushes, systemic erythema. Of the 40 cases, 92.5% of patients had underlying diseases. Among them, malignant disease, immunodeficiency, and invasive operations increase the risk of infection. On the basis of the drug susceptibility results, the preferred antibiotics are quinolone, third generations of cephalosporins, carbapenems, and aminoglycoside. Last, patients with abdominal infections caused by Raoultella spp. mostly have a good prognosis after early use of sensitive antibiotics. Conclusions: According to existing literature reports, the main type of abdominal infection caused by Raoultella is biliary tract infection, and most patients have other underlying diseases. Malignancy, immune deficiency, and invasive procedures are risk factors for bacterial infections. This review also emphasizes that Raoultella spp. is a rarely found opportunistic pathogen, which can cause a high incidence of healthcare-associated infections after invasive procedures. [ABSTRACT FROM AUTHOR]

Access to accurate statistical data is paramount in the pursuit of effective cancer control activities, including research, policy development, and clinical care. This paper presents a comprehensive statistical report on the incidence, mortality, survival, and treatment of major digestive organ cancers, including those of the esophagus, stomach, colon, rectum, liver, extrahepatic biliary tract, and pancreas, in Japan. We compiled data from the National Cancer Center's "Cancer Information Services" and government "e‐Stat" websites and offered a succinct overview of basic statistics by using tables and graphical presentations. Our findings underscore the critical role of the National Cancer Registry introduced by the Cancer Registry Act of 2016, which mandates hospitals across Japan to report cancer cases. This system ensures more accurate incidence statistics. Mortality data sourced from the National Vital Statistics System and survival rates derived from hospital‐based cancer registries offer insights into the outcomes and efficacy of treatment modalities. These data indicate a downward trend in mortality for stomach and liver cancers and stable or declining rates for other cancers except pancreatic cancer, which has the lowest survival rate. Treatment patterns indicate an increase in endoscopic procedures for esophageal and stomach cancers, with stable treatment approaches for colorectal cancer. This statistical overview aims to improve the understanding and inform research, policy, and clinical decisions in the field of digestive organ cancers. [ABSTRACT FROM AUTHOR]

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Background/Aims: Hepatobiliary scintigraphy (HBS) is used to evaluate bile excretion. This study aimed to evaluate biliary excretion during endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using HBS. Methods: We retrospectively evaluated 78 consecutive patients with malignant extrahepatic biliary obstruction, who underwent HBS after EUS-HGS between April 2015 and July 2022. The peak time and decay rate were scored with 0, 1, or 2 points based on thresholds of 20 and 35 minutes, and 10% and 50%, respectively. A total score of 4 or 3 was considered indicative of good bile excretion, whereas scores of 2, 1, or 0 indicated poor bile excretion. Results: The good and poor bile excretion groups included 40 and 38 cases, respectively. The group with good bile excretion had a significantly longer time to recurrent biliary obstruction compared to the poor bile excretion group (not reached vs. 124 days, p=0.026). Multivariate analysis identified the site of obstruction as a significant factor influencing good bile excretion (odds ratio, 3.39; 95% confidence interval, 1.01–11.4, p=0.049), with superior bile excretion observed in cases involving upper biliary obstruction compared to middle or lower biliary obstruction. Conclusions: In patients with malignant biliary obstruction who underwent HGS, the site of obstruction is significantly associated with stent patency. [ABSTRACT FROM AUTHOR]