Hepatobiliary & Pancreatic Diseases International最新文献

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality worldwide. Its etiology is complex, involving multiple aspects such as viral infection, dietary exposure, chemical pollution, lifestyle and endogenous factors. This review conducted a comprehensive search in databases such as PubMed and Scopus using keywords including "hepatocellular carcinoma", "environmental factors", "epidemiological trends", and "prevention and treatment strategies". Relevant papers, including clinical case reports, reviews, and basic research, were included. This study systematically reviewed the mechanisms and epidemiological characteristics of external environmental factors such as viral infection, aflatoxin, arsenic, vinyl chloride, per- and polyfluoroalkyl substances, microplastics, oral contraceptives, nitrite, and microcystin-leucine arginine in the occurrence of HCC; internal environmental factors such as genetic susceptibility, diabetes, obesity, metabolic dysfunction-associated steatotic liver disease, metabolic syndrome, gut microbiota, and sex hormones; other factors such as alcohol consumption, smoking, insufficient sleep, lack of exercise and aging. A variety of preventive and intervention measures have been proposed, including hepatitis B vaccination, reduction of aflatoxin and alcohol exposure, tobacco control, antioxidant supplementation, regular rest and exercise. The prevention and control of HCC should range from infectious disease prevention and control to metabolic disease management and environmental governance, combined with individualized risk assessment and precise prevention strategies.

Background: Precise preoperative risk stratification is critical for hepatocellular carcinoma (HCC) patients undergoing hepatectomy. This multicenter study aimed to develop and validate a laboratory-based prognostic score for survival prediction in patients undergoing hepatectomy for HCC.

Methods: Patients who underwent curative hepatectomy between January 2015 and December 2022 from six hospitals were divided into the training and validation cohorts. Preoperative laboratory parameters were analyzed by univariate and multivariate Cox regression. Based on alpha-fetoprotein (AFP, A), protein induced by vitamin K absence or antagonist-II (PIVKA-II, P), albumin (ALB, A), aspartate aminotransferase (AST, S), and total bilirubin (TBIL, L), we constructed a prognostic model named APASL. The prognostic performance was assessed using concordance index (C-index), time-dependent receiver operating characteristic curves, and calibration plots.

Results: A total of 1669 patients undergoing curative hepatectomy for HCC were included, 1239 as the training cohort and 430 as the validation cohort. The APASL score showed strong prognostic performance, with C-indices of 0.702 and 0.706 for predicting 5-year survival in the training and validation cohorts, respectively. X-tile analysis identified an optimal cutoff of 1.6, effectively separating patients into low-risk (≤ 1.6) and high-risk (> 1.6) groups, with significant differences in 5-year survival rates (61.4% vs. 37.2%, P < 0.001). The APASL score demonstrated superior predictive accuracy compared with conventional staging systems (TNM, BCLC, CLIP and Milan) and liver-function-based scores (ALBI and APRI). Multivariate Cox analysis confirmed that a high APASL score (> 1.6) was independently associated with decreased overall survival (hazard ratio: 1.248, 95% confidence interval: 1.036-1.502, P = 0.019).

Conclusions: The APASL score provides an effective, exclusively laboratory-based prognostic tool for predicting long-term survival after hepatectomy for HCC. This straightforward scoring system facilitates objective preoperative risk assessment without requiring histopathologic information, potentially improving surgical decision-making and patient counseling for patients with HCC.

Background: Hepatocellular carcinoma (HCC) in young patients is uncommon, and their postoperative prognosis remains poorly defined. This study aimed to evaluate the impact of young age on tumor characteristics, recurrence, and long-term outcomes after hepatectomy in patients with HCC.

Methods: We reviewed 5465 patients who underwent curative-intent hepatectomy for HCC at Asan Medical Center between December 2008 and March 2019. Patients were categorized into younger (< 40 years, n = 265) and older (≥ 40 years, n = 5200) groups. Clinicopathological characteristics, recurrence rates, overall survival (OS), and recurrence-free survival (RFS) were compared between groups before and after 1:10 propensity score matching (PSM). Multivariate logistic regression analysis was performed to identify independent predictors of 2-year recurrence.

Results: Younger patients were more likely to have hepatitis B virus-related HCC (81.1% vs. 65.3%, P < 0.001) and a lower prevalence of cirrhosis (38.5% vs. 45.9%, P = 0.018), and they exhibited a higher 2-year recurrence rate than older patients (39.6% vs. 31.7%, P = 0.007). Among patients within Milan criteria, younger patients showed superior OS (P = 0.028) and RFS (P = 0.013). In contrast, among patients beyond Milan criteria, younger patients had significantly poorer OS (P < 0.001) and RFS (P = 0.003) compared with older patients. These patterns persisted after PSM. Multivariate analysis identified age < 40 years as an independent predictor of 2-year recurrence in the beyond Milan criteria group, but not in the within Milan criteria group.

Conclusions: Young patients with HCC, particularly those beyond Milan criteria, were at increased risk of early recurrence and poorer long-term outcomes. These findings support the need for closer surveillance and tailored treatment strategies in this population.

Background: The optimal treatment strategy for hepatitis B surface antigen (HBsAg)-positive patients with unresectable intrahepatic cholangiocarcinoma (ICC) remains unclear. This study aimed to compare the efficacy and safety of FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin)-based hepatic arterial infusion chemotherapy (HAIC) versus first-line systemic chemotherapy (SC) in this population to identify a more effective treatment.

Methods: We included 165 HBsAg-positive patients with unresectable ICC treated at Sun Yat-sen University Cancer Center from July 2015 to April 2024. After propensity score matching, 68 patients were assigned to each group. The matched cohorts were compared in terms of progression-free survival (PFS), intrahepatic PFS, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.

Results: Compared to the SC group, the HAIC group demonstrated significantly longer median PFS (6.90 vs. 4.53 months; P < 0.001) and intrahepatic PFS (10.00 vs. 8.20 months; P = 0.006). The ORR was also significantly higher in the HAIC group according to both Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (38% vs. 15%; P = 0.004) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) (43% vs. 15%; P = 0.001) criteria. Conversion surgery was achieved in 14 patients (21%) in the HAIC group versus 1 patient (1%) in the SC group (P = 0.001). The incidence of any grade (P = 0.476) and grade 3-4 (P = 0.384) adverse events were comparable between the two groups.

Conclusions: In HBsAg-positive patients with unresectable ICC, FOLFOX-HAIC provided superior local control with a trend toward improved long-term prognosis compared to SC while maintaining an acceptable safety profile.

Background: Pancreatic tuberculosis is a rare entity. Most cases of pancreatic tuberculosis are documented in case reports. There has been no systematic analysis of the imaging characteristics of pancreatic tuberculosis, its association with abutting peripancreatic tuberculous lymphadenopathy, and its likely pathogenesis.

Data sources: A comprehensive search of pancreatic tuberculosis literature was conducted in MEDLINE, Embase and Scopus from 1978 to 2024. Manual searches of references in the published literature were also performed. The inclusion criteria for eligible cases comprised patient demographics, symptoms, imaging, pathology, microbiology, treatment and outcomes.

Results: A total of 252 eligible patients with pancreatic tuberculosis were identified, including 8 (3.2%) associated with miliary tuberculosis and 244 (96.8%) associated with non-miliary tuberculosis. Because the pathogenesis of miliary tuberculosis was distinct and hematogenous dissemination, only the 244 non-miliary tuberculosis patients were analyzed. Among these 244 patients, 61.5% were diagnosed in Asia and 69.2% younger than 50 years. The common symptoms were epigastric pain (79.5%) and weight loss (57.4%). In 244 patients, the most common imaging finding was a solitary mass (94.3%), with 84.8% occurring in the pancreatic head/uncinate process. The predominant imaging findings were heterogeneous lesions with ill-defined borders (77.7%), intralesional hypoechoic/anechoic areas on ultrasound (84.8%), and intralesional low-attenuation areas on contrast-enhanced computed tomography (CT) (86.4%). Peripancreatic tuberculous lymphadenopathies abutting pancreatic tuberculous lesion were observed in 89.3% of 244 patients. Pancreatic tuberculous lesions closely associated with peripancreatic abutting lymphadenopathy, observed in 198 (81.1%) patients. Among 95 patients who underwent surgery, 59 were found to be directly derived from their abutting lymphadenopathies.

Conclusions: Only a small proportion of patients with pancreatic tuberculosis are related to miliary tuberculosis. Pancreatic tuberculosis is more likely to originate from peripancreatic tuberculous lymphadenitis.

Background: The incidence and mortality rates of metabolic dysfunction-associated fatty liver disease (MAFLD) have been steadily increasing. Lactylation, a post-translational modification, has been implicated in lipid metabolism disorders. This study aimed to investigate the role of lactylation in the development of MAFLD and to elucidate the underlying mechanisms.

Methods: The relationship between lactate, lactylation, and MAFLD was explored using clinical MAFLD samples from First People's Hospital of Kunming City between March 2021 and September 2024. Proteomic sequencing of these samples was performed, and key proteins were identified by intersecting differentially expressed proteins in MAFLD with differentially modified lactylation sites. Subsequently, an in vitro cellular model of MAFLD was established. The involvement of the key gene methyl-CpG-binding protein 2 (MeCP2) in the MAFLD-lactylation mechanism was assessed using various techniques, including the CCK-8 assay, Oil Red O staining, Bodipy 493/503 fluorescence staining, Western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and co-immunoprecipitation (CO-IP).

Results: The key gene MeCP2 was identified by intersecting differentially expressed proteins in MAFLD with lactylation-modified proteins. In MAFLD liver tissue, we observed lactate accumulation, increased lactylation, and elevated MeCP2 expression. In the in vitro MAFLD cell model, lactate was found to promote lactylation, increase MeCP2 expression, and facilitate progression in a dose-dependent manner. Interference with MeCP2 expression inhibited acetyl-CoA carboxylase/fatty acid synthase (ACC/FAS)-mediated lipogenesis while enhancing peroxisome proliferator-activated receptor-α (PPARα)-mediated lipid oxidation. Furthermore, MeCP2 was found to interact with the lactylation-associated protein pan-Kla. Inhibition of MeCP2 suppressed lipid formation by reducing lactylation, thus ameliorating the progression of MAFLD.

Conclusions: Targeting MeCP2 expression improves the pathophysiology of MAFLD by downregulating lactylation, inhibiting ACC/FAS-mediated lipid synthesis, and promoting PPARα-mediated lipid oxidation.

Background: Biliary tract cancer (BTC) has a high postoperative recurrence rate and limiting long-term survival. Accurate prediction of recurrence is vital for clinical management. Carbohydrate antigen 19-9 (CA19-9) and the neutrophil percentage-to-albumin ratio (NPAR) are established prognostic markers in various cancers, but their combined value in BTC remains unclear. This study assessed the predictive role of the combination of CA19-9 and NPAR on time to recurrence (TTR) and introduced the novel NPAR-CA19-9 stratified score (NCSS).

Methods: A total of 145 BTC patients who underwent resection between March 2019 and December 2023 were analyzed. Preoperative blood samples, collected within two weeks of surgery, were used to measure CA19-9 and NPAR. Cutoff values were defined using the Maximum Selected Rank Statistic (MSRS). NCSS (0-2) were assigned according to marker levels and evaluated using Kaplan-Meier survival analysis and Cox regression models.

Results: Higher NCSS were associated with shorter TTR and reduced overall survival (P < 0.001). Cox regression confirmed NCSS as an independent predictor of recurrence [NCSS = 1: hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.05-3.14; NCSS = 2: HR = 2.95, 95% CI: 1.54-5.64] and overall survival (NCSS = 1: HR = 5.21, 95% CI: 1.19-22.82; NCSS = 2: HR = 11.88, 95% CI: 2.44-57.75). Subgroup analysis showed that patients with NCSS = 1 or 2 benefited from adjuvant chemotherapy, whereas those with NCSS = 0 did not. Incorporating NCSS into a nomogram improved prediction of TTR compared with a model excluding NCSS (C-index: 0.72 vs. 0.70; P = 0.027).

Conclusions: NCSS is a novel, simple, and effective preoperative scoring system that predicts TTR and overall survival in BTC patients, supporting more individualized treatment planning.