Search Results (570)

Hepatic abscesses are uncommon in dogs and typically develop secondary to biliary tract disease or ascending bacterial infections. Although congenital extrahepatic portosystemic shunt (EHPSS) is known to impair hepatic perfusion and immune clearance, its potential role in predisposing geriatric dogs to hepatic abscess formation has not been previously reported. This case report describes the diagnostic approach, therapeutic decision-making, and clinical outcome of a geriatric dog in which a multidrug-resistant hepatic abscess occurred in association with congenital EHPSS, and to propose a pathophysiologic link between chronic portal hypoperfusion and intrahepatic infection. An 11-year-old neutered male Maltese dog with a known EHPSS presented with acute anorexia and lethargy. Diagnostic imaging revealed a hepatic abscess adjacent to the gallbladder, and cytology confirmed a septic process. Despite targeted meropenem therapy based on antimicrobial susceptibility testing, the abscess failed to regress and C-reactive protein levels continued to rise. Concern for persistent biliary contamination and impaired hepatic immune clearance led to surgical intervention. A combined procedure—partial hepatic lobectomy, cholecystectomy, and shunt attenuation—was performed. Postoperative hypotension was managed successfully with vasopressors and transfusion. The patient recovered uneventfully, and at four-month follow-up, hepatic enzyme activities normalized and liver size increased. These findings highlight the need to evaluate hepatic infections in dogs with EHPSS as a potential consequence of impaired hepatic immune clearance rather than an incidental finding. Full article

Background: Durvalumab combined with gemcitabine–cisplatin (GC) has become the standard first-line treatment for advanced biliary tract cancer (BTC) following the TOPAZ-1 trial. However, real-world effectiveness, safety, and prognostic determinants, particularly in underrepresented populations, remain insufficiently defined. The aim of this study was to evaluate the real-world outcomes of first-line durvalumab plus chemotherapy and identify independent prognostic factors in patients with advanced BTC. Methods: This multicenter retrospective cohort study included patients with unresectable or metastatic BTC treated with first-line durvalumab plus chemotherapy across 21 tertiary oncology centers in Türkiye. Clinical characteristics, laboratory parameters, biomarker data, and treatment details were collected. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Survival outcomes were analyzed using the Kaplan–Meier method and Cox proportional hazards regression models. Results: A total of 78 patients were analyzed; 53.8% were male, and the median age was 62 years. Primary tumor sites were intrahepatic (55.1%), extrahepatic (30.8%), and gallbladder (14.1%). After a median follow-up of 12.58 months, median OS was 11.59 months and median PFS was 6.80 months. The ORR was 50.6%, including complete and partial responses in 2.7% and 47.9% of patients, respectively. Treatment-related adverse events occurred in 97.4% of patients, with grade 3–4 events in 37.2%. Immune-related adverse events were observed in 19.2%, including one case of grade 3 pneumonitis. No patient permanently discontinued durvalumab due to toxicity, and no durvalumab-related mortality occurred. In multivariable analysis, ECOG performance status 2 (HR 3.43; 95% CI 1.33–8.80) and ALBI grade 2–3 (HR 2.54; 95% CI 1.24–5.19) independently predicted worse OS, while ECOG performance status 2 also predicted shorter PFS (HR 5.91; 95% CI 2.30–15.17). Conclusions: In this multicenter real-world Turkish cohort, first-line durvalumab plus chemotherapy showed effectiveness and tolerability comparable to clinical trial data. Baseline ECOG performance status and ALBI grade were independent prognostic factors, supporting their use for risk stratification in advanced biliary tract cancer. Full article

Background/Objectives: To present, discuss, and illustrate the role of multiparametric magnetic resonance imaging (MPMRI) in the evaluation of biliary tree (BT) complications after liver transplantation (LT) as an integrated part into the multidisciplinary team approach for personalized patients’ treatment. Methods: We retrospectively analyzed the MPMRI findings of 317 patients out of 1080 cases with LT, admitted to the Fundeni Clinical Institute from January 2005 to June 2025, who developed biliary complications. Results: Biliary complications after LT evaluated by MPMRI included anastomotic strictures in 235 cases (74%), intra- or extrahepatic bile leaks/biloma in 56 patients (18%), secondary cholangitis due to pyogenic cholangitis in 91 cases (29%), liver abscesses in 23 patients (7%), BT lithiasis in 27 patients (8.5%), disease recurrence in 26 cases (8%), and extrinsic BT compression in 1 case (0.3%). Conclusions: MPMRI plays a crucial role for the evaluation of BT complications, with the protocol being optimized in correlation with the clinical question or suspicion and with the clinical status of the patient. Full article

3-Ketoacid CoA-transferase 1 (OXCT1) is a homodimeric mitochondrial matrix enzyme essential for ketone body metabolism. It catalyzes the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate, playing a central role in extrahepatic ketone body catabolism. Accumulating evidence indicates that OXCT1 is dysregulated in various cancers, where it functions as an oncogene, driving tumor progression by modulating proliferation, metastasis, apoptosis, autophagy, and drug resistance. Its overexpression is associated with aggressive tumor behavior, metabolic adaptation, and poor clinical outcomes. This review systematically summarizes the molecular structure, biological functions, and regulatory mechanisms of OXCT1, highlighting its multifaceted roles in tumorigenesis and progression. Furthermore, we discuss its potential as a diagnostic biomarker, prognostic indicator, and therapeutic target, providing novel insights for developing OXCT1-based anticancer strategies. Full article

Background: This study aimed to analyse treatment outcomes, determine prognostic factors and assess the toxicity of reirradiation using high-dose-rate (HDR) brachytherapy for liver metastases in the oligometastatic stage of disease. Materials and Methods: The study included 59 patients who had previously undergone SBRT (stereotactic body radiation therapy) or HDR brachytherapy and experienced progression within (type 1) or outside (type 2) the irradiated area, but in a different location within the liver. Patients were divided according to the type of reirradiation and the reason for treatment. Local control (LC), progression-free survival (PFS) and overall survival (OS) were analysed in relation to the following factors: age; gender; performance status; tumour type; line of systemic treatment; location of extrahepatic metastases; type of reirradiation; time since previous irradiation; indication for treatment; size and number of metastases; dose; and degree of response to treatment. Treatment toxicity and the influence of dose, irradiation volume, number of metastases, time since previous radiotherapy and dose to the non-irradiated part of the liver on hepatic toxicity were also assessed. Results: With a median follow-up period of 13 months, the median LC, PFS and OS were 9, 8 and 13 months, respectively. The respective rates of partial regression (PR), stable disease (SD) and progressive disease (PD) were 32%, 44% and 12%. The most significant factors influencing LC were the degree of tumour shrinkage, with PFS influenced by the degree of tumour shrinkage and a low number of metastases, and OS influenced by the degree of tumour shrinkage, a low number of metastases and one to two lines of systemic therapy. Treatment toxicity was low, and there was no strong correlation between the dosimetric parameters of the treatment plan and the biochemical parameters of liver function. Conclusions: Brachytherapy is a safe and effective method of re-irradiating liver metastases. However, due to the limitations of the study, further investigation is required. Full article

A 50-year-old woman presented a rapidly proliferative cystic lesion in the left pelvis as displayed by sonography. Exploratory laparoscopy with omental biopsy suggested pseudomyxoma peritonei (PMP). An ¹⁸F-FDG PET/CT revealed scalloping of the liver surface with an associated extrahepatic lesion exhibiting moderate FDG avidity and strand-like FDG uptake within a left-sided septated ovarian cyst. The diagnosis of low-grade appendiceal mucinous neoplasms was proven after cytoreductive surgery. This case provided important imaging features on ¹⁸F-FDG PET/CT that directed the pre-operative diagnosis and the initiation of treatment. Full article

Ferroptosis has emerged as a promising therapeutic vulnerability of diverse malignancies, yet the regulatory circuits adopted by each in cholangiocarcinoma (CCA) subtypes remain incompletely understood. We integrated the genome-wide CRISPR–Cas9 loss-of-function screens and transcriptomic profiles of the Cancer Dependency Map and then systematically assessed the essentiality of ferroptosis suppressor genes (FSGs) in the intrahepatic (iCCA) and extrahepatic (eCCA) subtypes. Nineteen and 16 essential FSGs were identified in iCCA and eCCA, respectively, among which GPX4 exhibited a significantly higher dependency in iCCA. Pharmacological inhibition of GPX4 with RSL3 markedly reduced cell viability and induced lipid peroxidation in iCCA cell lines, whereas eCCA cell lines displayed pronounced resistance associated with elevated GPX4 expression. A transcriptomic comparison revealed enrichment of WNT signaling in eCCA. Co-treatment with the tankyrase inhibitor XAV-939 and RSL3 enhanced growth inhibition of eCCA cells, indicating that WNT signaling contributed to ferroptosis resistance. These findings indicate that iCCA exhibits a preferential dependency on GPX4, whereas WNT–β-catenin signaling mediates resistance in eCCA. Collectively, the results clarify the molecular basis of subtype-specific ferroptosis vulnerability and offer a rationale for combinatorial therapeutic strategies that integrate GPX4 and WNT pathway inhibition when treating refractory eCCA. Full article

Background: JAK/STAT interferon signaling interacts with the PI3K/AKT/mTOR pathway to drive hepatocellular carcinoma (HCC) progression and metastasis. RSAD2, an interferon-inducible gene, is upregulated by the PI3K/AKT/mTOR pathway and serves as a key factor for metabolic reprogramming to promote stem-like properties of cancer stem cells and tumor proliferation. In patients with resected HCC, RSAD2 upregulation showed an association with microvascular invasion, which is a proven risk factor for developing HCC metastasis. This clinical observation was compatible with preclinical findings. On the other hand, RSAD2 upregulation has been reported to confer poor prognosis in breast and gastric cancers. However, further clinical study of RSAD2 in HCC is lacking. As a result, we investigated the clinical implications of RSAD2 gene expression in HCC patients, in terms of its associations with survival, the presence of extra-hepatic metastasis, and other clinical manifestations. Methods: We studied 309 treatment-naïve HCC patients, as well as data from the TCGA and GTEx databases. Results:RSAD2 gene expression was differentially upregulated in HCC tumors when compared to normal liver tissues (p < 0.01). Elevated RSAD2 mRNA levels in the blood and the presence of extra-hepatic metastasis were independent prognostic factors for poor overall survival (OS) (p < 0.01). The median OS of patients with high RSAD2 expression vs. low expression were 5.4 vs. 14.2 months, respectively (p < 0.01). A high RSAD2 mRNA level was significantly correlated with the presence of extra-hepatic metastasis, nutritional disturbance, and functional impairment after controlling for confounding clinical factors (p < 0.05). Conclusions: High RSAD2 gene expression is associated with poorer OS, the presence of extra-hepatic metastasis, and quality-of-life disturbances in HCC patients. Full article

Androgen receptor (AR) signaling has a pivotal role in hepatic lipid homeostasis, as well as in core metabolic functions such as lipogenesis, fatty acid oxidation, and insulin sensitivity. Dysregulation of AR function has been demonstrated in both animal and human studies to disrupt these crucial metabolic pathways, thereby promoting hepatic steatosis. Several causes can lead to AR dysregulation, including genetic mutations or polymorphisms, epigenetic and post-transcriptional modifications, as well as various endocrine disturbances. Prompted by a diagnostically challenging case of a lean 34-year-old male with persistent ALT-predominant transaminasemia, unexplained suboptimal dyslipidemia despite adherence to drug therapy and a healthy lifestyle, and chronically elevated creatine phosphokinase levels irrespective of statin use or exercise intensity, we highlight the overlooked mechanistic link between AR dysfunction and liver–muscle disruption in lean-MASLD patients. Considering the pivotal role of AR in liver–muscle crosstalk, we emphasize the importance of evaluating AR signaling pathways through targeted genetic testing in cases of lean-MASLD among the male population, as well as addressing other extrahepatic manifestations, such as neuromuscular diseases, closely related to AR dysfunction. This clinical strategy may ultimately optimize lean-MASLD management, particularly in view of the emerging utilization of AR-targeted therapeutic modalities, and may also facilitate the management of systemic manifestations associated with altered AR signaling pathways. Full article

Background and Objectives: Cholangiocarcinoma (CCA) is an aggressive tumor that originates in the biliary tract and is subdivided anatomically into intrahepatic (iCCA) and extrahepatic (perihilar-pCCA and distal-dCCA). Diagnosis remains challenging, particularly for extrahepatic forms (pCCA and dCCA). We aimed to assess the relation between systemic inflammatory markers—specifically lymphocyte-related ratios—and tumor characteristics in a Romanian cholangiocarcinoma cohort. Materials and Methods: We conducted an exploratory single-center study including adult patients with a confirmed CCA histopathological diagnosis. We excluded patients with an uncertain diagnosis or tumors of the ampulla of Vater or gallbladder. Demographic and clinical data were retrospectively collected from medical records. Results: Tumor localization was the strongest predictor of metastatic disease. The odd of metastasis was 7.3 times higher for iCCA than dCCA and 4.5 times higher for iCCA than pCCA. Although several evaluated inflammatory biomarkers showed statistically significant associations, their clinical relevance was limited. The odds ratios for these biomarkers were characterized by lower bounds near the null value and wide confidence intervals, reflecting considerable patient heterogeneity, model instability, and inconclusive effect sizes. Conclusions: Our findings suggest a potential biological link between systemic inflammation, metastatic spread, and tumor differentiation grade that deserves further investigation using more accurate systemic inflammation biomarkers than those routinely collected. Full article

Primary biliary cholangitis (PBC) is a heterogeneous autoimmune liver disease in which clinical presentation, disease progression, and response to therapy vary markedly from patient to patient. This heterogeneity reflects its complex, multifactorial, and not-completely elucidated pathogenesis. Currently, serological markers are available to non-invasively diagnose PBC, reserving liver biopsy for selected cases with atypical presentations or diagnostic uncertainty. Anyway, the accurate non-invasive prediction of liver-related and non-liver-related (i.e., extra-hepatic, including pruritus) outcomes remains an open challenge, as well as an urgent need, considering the great variability in clinical course and prognosis reported in PBC patients. Moreover, although ursodeoxycholic acid (UDCA) remains the standard first-line treatment, not all individuals respond equally, either in terms of therapeutic efficacy or timing of biochemical improvement. This further variability in treatment response underscores the inadequacy of uniform management approaches and reinforces the urgent need for personalized medicine, where treatment decisions are guided by patient-specific biological and clinical parameters. In this scenario, the identification and validation of non-invasive predictive biomarkers capable of detecting early therapeutic responsiveness are pivotal for optimizing care pathways. Finally, a growing portion of patients show an insufficient UDCA response or are UDCA intolerant, making the identification of novel strategies of care an urgent need. Concerning this, very recently, new therapeutic options beyond UDCA targeting, among the other pathways, bile acid metabolism (including the modern Peroxisome Proliferator-Activated Receptor agonists), immune regulation, and fibrogenesis, have expanded the treatment landscape. In the Era of Precision Medicine, these diagnostic, prognostic, and therapeutic innovations, by reflecting the complexity of PBC pathogenesis, underline the cruciality of a patient-tailored strategy to improve outcomes and mitigate disease progression. The present review reports recent advances, highlights ongoing challenges, and outlines future perspectives in the management of PBC. Full article

Background: Hepatitis C (HC) remains a major public health concern, affecting approximately 50 million people globally. In addition to hepatic damage, HC induces extrahepatic manifestations (EHMs), including oral conditions such as oral lichen planus (OLP), xerostomia, and Sjögren syndrome-like (SS-like), which impair quality of life. The aim of this study was to investigate the possible association between certain extrahepatic manifestations of HC and the presence of risk factors. Methods: A cross-sectional study was conducted on 38 adults (22 males and 16 females; mean age 56.5 ± 8.6 years) with inactive HC. For each patient, demographic and clinical data were collected, including the following: frequency of dental brushing, frequency of professional dental hygiene visits, smoking, alcohol consumption, the presence of xerostomia, OLP, and SS-like. Logistic regression analyses and ROC curves were performed using R software to identify independent predictors for each condition. Results: OLP was present in 39.5%, xerostomia in 47.4%, and SS-like in 15.8% of patients. Female gender significantly predicted OLP and showed a borderline association with xerostomia. Smoking was weakly associated with xerostomia. No predictors were significant for SS-like. Conclusions: Oral hygiene and smoking are risk factors for oral EHM, their good control being important for the quality of life of these patients. Gender has also been shown to be a risk factor for these manifestations. Full article

Despite improved therapeutic concepts, the survival of patients with hepatocellular carcinoma (HCC) is limited. Liver transplantation (LT) is the best possible treatment for suitable patients. This therapy is of particular importance, because it not only removes the cancer but also cures the underlying structural liver disease. Due to the persistent lack of donor organs, however, the oncological prognosis after LT is of particular importance for fair organ allocation. Bonus points on the organ waiting list are rewarded for tumors within a certain tumor extent. In general, macrovascular invasion and extrahepatic tumor manifestation are considered to be contraindications for LT, as survival in these patients is very low. In recent years, however, microvascular invasion and poorly differentiated tumors have also turned out to be unfavorable. Most selection criteria for LT in HCC are still based on very simple imaging criteria like size and number without utilizing additional imaging characteristics inherent to the tumor nodule, which could be processed in a “virtual biopsy”. Recently, diagnostic research has presented the clinical benefit of artificial intelligence (AI) in the use of deep-learning strategies for digital diagnosis of poorly differentiated or microvascular-infiltrated tumors. In addition, evaluation of TACE response is analyzed as a possibility to estimate LT survival. The aim of this review is to provide an overview of recent advances in HCC diagnosis and to classify the clinical relevance of these diagnostic and technical advances. Secondly, we discuss how these advances could affect the organ allocation process. Full article

Unresectable extrahepatic cholangiocarcinoma remains a challenging malignancy with limited therapeutic options and poor prognosis. In this setting, effective and durable biliary drainage is crucial to prevent cholangitis, allow timely initiation and maintenance of systemic therapy, and ultimately improve survival. Endobiliary radiofrequency ablation (RFA) has emerged as a promising adjunct to biliary stenting, aimed at delaying tumor ingrowth and prolonging stent patency through localized thermal ablation of malignant tissue. Several studies have reported longer stent patency and, in some cases, improved survival with RFA plus stenting compared with stenting alone. However, the literature remains heterogeneous, and recent high-quality trials have yielded conflicting results, highlighting the need for further standardization of technique and patient selection. This narrative review summarizes the current evidence on the role of endobiliary RFA in unresectable cholangiocarcinoma, with particular emphasis on mechanism of action, endoscopic technique and oncologic outcomes. Full article