Search Results (7)

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies of the biliary tract, often originating from chronic inflammation associated with gallstones and cholecystitis. Persistent inflammation plays a pivotal role in the development of preneoplastic changes, such as metaplasia, which may progress to malignancy. Despite its relatively low incidence, GBC is characterized by a poor prognosis due to late-stage diagnosis, highlighting the urgent need for improved early detection strategies. This study aimed to assess the diagnostic and prognostic significance of CA 19-9 and CEA levels in patients with gallbladder lesions, while also evaluating systemic inflammation and hemostatic dysregulation. A retrospective analysis was conducted on patients diagnosed with gallbladder lesions, with histopathological confirmation of adenocarcinoma and metaplasia. Laboratory assessments included serum levels of tumour markers, inflammatory markers such as CRP, and key hemostatic parameters, including thrombocyte count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen levels. A predictive scoring model was developed using the cutoff values of CA 19-9 and CEA to assess their combined diagnostic potential. Among the patients studied, 48.9% had an initial diagnosis of chronic cholecystitis, while 32.2% presented with acute cholecystitis. Adenocarcinoma was identified in 6.7% of cases after histopathological examination, predominantly in females over 65 years old with acute cholecystitis. Metaplasia was detected in 7.8% of cases, primarily in elderly females with chronic cholecystitis. Laboratory findings revealed significantly elevated levels of CA 19-9, CEA, AFP, and CA-125 in patients with adenocarcinoma. Additionally, abnormalities in hemostatic parameters, including increased fibrinogen levels and alterations in thrombocyte count, were observed in patients with malignancy. A combined predictive score using CA 19-9 and CEA demonstrated strong potential for detecting adenocarcinoma and metaplasia, improving diagnostic accuracy. Our findings emphasize the clinical importance of integrating tumour markers, inflammatory biomarkers, and hemostatic parameters in the evaluation of gallbladder lesions associated with chronic inflammation. The combined assessment of these factors enhances early detection, facilitates malignancy risk stratification, and improves prognostic evaluation, particularly in patients with metabolic and cardiovascular comorbidities. Full article

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

(1) Background: Nonalcoholic Steatohepatitis/Nonalcoholic Fatty Liver Disease (NASH/NAFLD) is the most recurrent chronic liver disease. NASH could present with a cholestatic (C) or hepatic (H) pattern of damage. Recently, we observed that increased Epithelial Cell Adhesion Molecule (EpCAM) expression was the main immunohistochemical feature to distinguish C from H pattern in NASH. (2) Methods: In the present study, we used digital pathology to compare the quantitative results of digital image analysis by QuPath software (Q-results), with the semi-quantitative results of observer assessment (S-results) for cytokeratin 7 and 19, (CK7, CK19) as well as EpCAM expression. Patients were classified into H or C group on the basis of the ratio between alanine transaminase (ALT) and alkaline phosphatase (ALP) values, using the “R-ratio formula”. (3) Results: Q- and S-results showed a significant correlation for all markers (p < 0.05). Q-EpCAM expression was significantly higher in the C group than in the H group (p < 0.05). Importantly ALP, an indicator of hepatobiliary disorder, was the only biochemical parameter significantly correlated with Q-EpCAM. Instead, Q-CK7, but not Q-CK19, correlated only with γGlutamyl-Transferase (γGT). Of note, Stage 4 fibrosis correlated with Q-EpCAM, Q-CK19, and ALP but not with γGT or ALT. Conclusions: Image analysis confirms the relation between cholestatic-like pattern, associated with a worse prognosis, with increased ALP values, EpCAM positive biliary metaplasia, and advanced fibrosis. These preliminary data could be useful for the implementation of AI algorithms for the assessment of cholestatic NASH. Full article

Barrett’s esophagus (BE) is a premalignant lesion that can develop into esophageal adenocarcinoma (EAC). The development of Barrett’s esophagus is caused by biliary reflux, which causes extensive mutagenesis in the stem cells of the epithelium in the distal esophagus and gastro-esophageal junction. Other possible cellular origins of BE include the stem cells of the mucosal esophageal glands and their ducts, the stem cells of the stomach, residual embryonic cells and circulating bone marrow stem cells. The classical concept of healing a caustic lesion has been replaced by the concept of a cytokine storm, which forms an inflammatory microenvironment eliciting a phenotypic shift toward intestinal metaplasia of the distal esophagus. This review describes the roles of the NOTCH, hedgehog, NF-κB and IL6/STAT3 molecular pathways in the pathogenesis of BE and EAC. Full article

This article systematizes available data from the literature on biliary gastritis (BG) in order to increase the awareness of specialists about the latest possibilities for diagnosing the disease. BG occurs as a result of pathological duodenogastric reflux. In patients with a preserved duodenogastric junction, the dominant factor is represented by motor disorders of the upper digestive tract (primary biliary gastritis), while in patients recovering from surgical interventions it is represented by structural changes (secondary biliary gastritis). Progressive BG can lead to atrophy of the gastric mucosa, intestinal metaplasia, epithelial dysplasia, and eventually to gastric cancer. Diagnostic methods for BG are carried out to identify risk factors, exclude alarm symptoms and identify persistent motor disorders and pathological reflux (24 h pH-impedancemetry, hepatobiliary scintigraphy, 24 h monitoring of bilirubin content in the reflux using a Bilitec 2000 photometer), as well as to diagnose gastritis itself (esophagogastroduodenoscopy, morphological gastrobiopsy examination). The diagnosis of BG should be based on a multidisciplinary approach that combines a thorough analysis of a patient’s complaints, an anamnesis of the disease, and the results of endoscopic and histological research methods. Full article

The small liver fluke Clonorchis sinensis causes hepatobiliary ductal infections in humans. Clonorchiasis is characterized histopathologically by ductal dysplasia, hyperplasia and metaplasia, which closely resembles cholangiocarcinoma (CCA). The disruption of programmed cell death is critical for malignant transformation, while molecular events underlying these phenomena have poorly been understood in clonorchiasis-related CCA tumorigenesis. We incorporated recombinant C. sinensis omega-class glutathione transferase (rCsGSTo) 1 or 2 into human intrahepatic biliary epithelial cells (HIBECs) and analyzed pathophysiological alterations of HIBECs upon the application of oxidative stress. rCsGSTos partially but significantly rescued HIBECs from cell death by inhibiting oxidative stress-induced apoptosis (p < 0.01). rCsGSTos modulated transcriptional levels of numerous genes. We analyzed 13 genes involved in programmed cell death (the upregulation of five antiapoptotic and two apoptotic genes, and the downregulation of one antiapoptotic and five apoptotic genes) and 11 genes associated with cell differentiation (the increase in seven and decrease in four genes) that showed significant modifications (p < 0.05). The induction profiles of the mRNA and proteins of these differentially regulated genes correlated well with each other, and mostly favored apoptotic suppression and/or cell differentiation. We detected increased active, phosphorylated forms of Src, PI3K/Akt, NF-κB p65, MKK3/6 and p38 MAPK, but not JNK and ERK1/2. CsGSTos were localized in the C. sinensis-infected rat cholangiocytes, where cytokeratin 19 was distributed. Our results demonstrated that CsGSTos excreted to the biliary lumen are internalized and accumulated in the host cholangiocytes. When cholangiocytes underwent oxidative stressful condition, CsGSTos appeared to be critically involved in both antiapoptotic process and the differentiation of host cholangiocytes through the regulation of target genes following the activation of responsible signal molecules. Full article

The concomitant occurrence of duodenal atresia (DA) and a choledochal cyst (CC) has rarely been reported. Knowledge of both the presentation and management of this rare co-occurrence is imperative in avoiding potential complications and sequelae, such as biliary metaplasia. Herein we describe a female infant born at 32 weeks gestational age who was diagnosed with duodenal atresia and annular pancreas postnatally, who had subsequent findings of malrotation and a choledochal cyst, as seen from contrast imaging. Uncomplicated repair of the DA and obstruction was performed at 4 days of life. She re-presented 2 years later with non-bloody, nonbilious emesis and was found to have elevated amylase, lipase and liver enzymes. Imaging revealed dilated intra-hepatic ducts, a distended gallbladder and a large choledochal cyst. She underwent a cholecystostomy tube placement followed by a definitive choledochal cyst excision with immediate improvement following surgery and full resolution of symptoms before discharge. Full article