Kuang-Chun Hu

Combined hepatocellular–cholangiocarcinoma (cHCC-CCA) is a rare and highly aggressive primary liver cancer. It is distinguished by the unequivocal coexistence of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) components within a single tumor. cHCC-CCA accounts for between 0.4% and 14.2% of primary liver cancers, presenting a complex clinical and pathological challenge because of its dual histological morphology and phenotypic diversity. In the past, its classification faced significant diagnostic challenges. However, these issues have been largely addressed by the 2019 World Health Organization 5th Edition reclassification, which requires clear differentiation of hepatocytic and cholangiocytic features using hematoxylin and eosin (H&E) staining. Recent genomic profiling has shown that cHCC-CCA exists on a molecular spectrum, with about 75% of individual tumors being HCC-like or CCA-like. Biliary-dominant subtypes, similar to CCA, often contain actionable alterations like FGFR2 fusions, IDH1 mutations, and HER2 amplification, providing significant opportunities for precision oncology. In contrast, subtypes resembling HCC are commonly driven by mutations in TP53 and the TERT promoter. Major hepatectomy combined with regional lymphadenectomy continues to be a fundamental curative treatment. However, liver transplantation is increasingly being recognized as a viable option for carefully selected patients with early-stage cirrhosis. In the advanced or recurrent stage, the traditional preferred treatment continues to be cytotoxic gemcitabine combined with platinum-based therapies. Meanwhile, combinations involving immune checkpoint inhibitors, like atezolizumab and bevacizumab, or more complex regimens that integrate locoregional therapy, TKIs, and PD-(L)1 inhibitors, offer hopeful prospects for improving survival rates. This review provided an overview of the current knowledge of the clinical classification, risk stratification, histogenesis, molecular biology and clinical management of cHCC-CCA to inform current management approaches and outline future paths in precision oncology.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and highly aggressive primary liver cancer. It is distinguished by the unequivocal coexistence of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) components within a single tumor. cHCC-CCA accounts for between 0.4% and 14.2% of primary liver cancers, presenting a complex clinical and pathological challenge because of its dual histological morphology and phenotypic diversity. In the past, its classification faced significant diagnostic challenges. However, these issues have been largely addressed by the 2019 World Health Organization 5th Edition reclassification, which requires clear differentiation of hepatocytic and cholangiocytic features using hematoxylin and eosin (H&E) staining. Recent genomic profiling has shown that cHCC-CCA exists on a molecular spectrum, with about 75% of individual tumors being HCC-like or CCA-like. Biliary-dominant subtypes, similar to CCA, often contain actionable alterations like FGFR2 fusions, IDH1 mutations, and HER2 amplification, providing significant opportunities for precision oncology. In contrast, subtypes resembling HCC are commonly driven by mutations in TP53 and the TERT promoter. Major hepatectomy combined with regional lymphadenectomy continues to be a fundamental curative treatment. However, liver transplantation is increasingly being recognized as a viable option for carefully selected patients with early-stage cirrhosis. In the advanced or recurrent stage, the traditional first-line treatment continues to be cytotoxic gemcitabine combined with platinum-based therapies. Meanwhile, combinations involving immune checkpoint inhibitors, like atezolizumab and bevacizumab, or more complex regimens that integrate locoregional therapy, TKIs, and PD-(L)1 inhibitors, offer hopeful prospects for improving survival rates. This optimism is supported by research indicating that 57% of tumors exhibit a high immune microenvironment. This review provided an overview of the current knowledge of the clinical classification, risk stratification, histogenesis, molecular biology and clinical management of cHCC-CCA to inform current multidisciplinary management approaches and outline future paths in precision oncology.

BACKGROUND Magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) are recommended in combination for screening pancreatic cancer in high-risk individuals. However, in clinical practice, MRI and EUS are increasingly utilized for pancreatic surveillance during routine health examinations. AIM To investigate the feasibility of these imaging modalities for screening in low-risk individuals. METHODS This retrospective study included patients at low risk for pancreatic cancer who underwent MRI or EUS at two health evaluation centers between March 2019 and December 2024. Basic characteristics, laboratory data, and imaging results were collected. RESULTS A total of 3364 low-risk individuals underwent pancreatic screening: 1553 (46.1%) received MRI, and 1811 underwent EUS. No significant differences were observed in age or sex distribution between the groups. In imaging screening, EUS demonstrated a higher detection rate of abnormal pancreatic lesions (12.8% vs 2.6%; P < 0.001). MRI detected more cystic lesions than did EUS (P < 0.001). EUS identified smaller nodular lesions compared to MRI (9.2 mm vs 18.0 mm; P = 0.044). The MRI group had a higher number of confirmed intraductal papillary mucinous neoplasms (P = 0.031), whereas the EUS group identified more suspected branch-duct intraductal papillary mucinous neoplasms (P < 0.001). Pancreatic adenocarcinoma was found in three patients (0.08%), with no significant difference in detection rates between EUS and MRI (0.11% vs 0.06%; P = 0.656). CONCLUSION In low-risk individuals, MRI and EUS offer comparable effectiveness for pancreatic cancer surveillance. The choice of imaging strategy for health evaluation depends on cost considerations and degree of invasiveness.

The risk factors for clinical outcomes of hepatocellular carcinoma (HCC) associated with metabolic-associated fatty liver disease (MAFLD) following hepatectomy remain uncertain. The association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and HCC recurrence and mortality remains unknown in this population. This retrospective cohort study enrolled 70 patients with MAFLD-related HCC who underwent hepatectomy between 2011 and 2022 at the E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Data analysis was completed in October 2023. The proposed criteria for the diagnosis of MAFLD are based on the evidence of hepatic steatosis (>5%) and one of the following 3 criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. The end points were HCC recurrence and overall mortality. Of the 70 patients enrolled, 55 (78.6%) were men, and the mean (standard deviation) age was 67.4 (8.0) years. HCC recurrence occurred in 19 patients, and 20 died. The 10-year cumulative HCC recurrence and mortality rates after resection were 55.4% and 43.9%, respectively. In Cox proportional analyses, patients with ALDH2 rs671 genotypes GA/AA had the highest HCC recurrence rate (hazard ratio [HR]: 3.48, 95% confidence interval [CI]: 1.08–12.4, P = .045), followed by those with multiple tumors (HR: 3.06, 95% CI: 1.11–10.9, P = .039). Moreover, patients with Barcelona clinic liver cancer stage B/C had the highest mortality rate (HR: 3.94, 95% CI: 1.34–11.6, P = .012), followed by those with hypertension (HR, 3.47; 95% CI: 1.28–9.40, P = .015). ALDH2 rs671 polymorphism and multiple liver tumors were strongly associated with HCC recurrence. Furthermore, Barcelona clinic liver cancer stage and hypertension were significantly associated with mortality in MAFLD-related HCC patients after hepatectomy.

The connection between microbial infections and tumor formation is notably exemplified by Helicobacter pylori (H. pylori) and its association with gastric cancer (GC) and colorectal cancer (CRC). While early studies hinted at a link between H. pylori and colorectal neoplasms, comprehensive retrospective cohort studies were lacking. Recent research indicates that individuals treated for H. pylori infection experience a significant reduction in both CRC incidence and mortality, suggesting a potential role of this infection in malignancy development. Globally, H. pylori prevalence varies, with higher rates in developing countries (80–90%) compared to developed nations (20–50%). This infection is linked to chronic gastritis, peptic ulcers, and GC, highlighting the importance of understanding its epidemiology for public health interventions. H. pylori significantly increases the risk of non-cardia GC. Some meta-analyses have shown a 1.49-fold increased risk for colorectal adenomas and a 1.70-fold increase for CRC in infected individuals. Additionally, H. pylori eradication may lower the CRC risk, although the relationship is still being debated. Although eradication therapy shows promise in reducing GC incidence, concerns about antibiotic resistance pose treatment challenges. The role of H. pylori in colorectal tumors remains contentious, with some studies indicating an increased risk of colorectal adenoma, while others find minimal association. Future research should investigate the causal mechanisms between H. pylori infection and colorectal neoplasia, including factors like diabetes, to better understand its role in tumor formation and support widespread eradication efforts to prevent both gastric and colorectal cancers.

Background: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. Methods: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. Results: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. Conclusions: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS.

Background and Objective: To assess whether the combination of high waist-to-hip ratio (WHR) and elderly age is associated with higher risk of GERD. Material and Methods: A total of 16,996 subjects aged ≥20 years who received esophagogastroduodenoscopy (EGD) between January 2010 and December 2019. We evaluated the risk of GERD in different age groups and WHR groups in unadjusted analysis and multivariate logistic regression models for predictors of GERD. Results: There was a trend towards more participants with both age ≥65 years and WHR ≥ 1 (n = 129) (n = 66, 51%) than participants with age < 65 and WHR < 0.9 (n = 10,422) (n = 2814, 27%) presenting with GERD. Participants who had both age ≥ 65 years and high WHR ≥ 1 had the highest risk of any type of GERD (adjusted OR, 2.07; 95% CI, 1.44–2.96, p value < 0.05) based on multivariate logistic regression analysis. Conclusions: The combination of having a high WHR and being elderly was associated with a higher risk of GERD, and preventing central obesity in the elderly population reduced the risk of GERD and the requirement for medical resources.

Brachial-ankle pulse wave velocity (baPWV) is used for predicting the severity of vascular damage and prognosis of atherosclerotic cardiovascular disease (ASCVD) in people with hypertension and diabetes mellitus. This correlation study aimed to compare the baPWV with other risk indicators for identification of subclinical vascular disease for primary prevention and to determine the clinical utility of baPWV-guided therapy in improving prognosis in high-risk subjects. We included 4881 subjects who underwent voluntary health examination at Mackay Memorial Hospital, Taiwan between 2014 and 2019. Participants were categorized into the low-risk (P < .001). The mean estimated glomerular filtration rate decreased significantly from the low- to high-risk groups (P < .001). The predicted vascular age and actual age differed significantly between the intermediate- and high-risk groups (P < .001). High-density lipoprotein levels plummeted significantly among the 4 groups (P < .001). The right and left baPWV and ankle brachial index differed significantly among the 4 groups (all P < .001) and increased from the low-risk to high-risk groups (P < .001). Carotid Doppler ultrasonography revealed a significant increase in plaque formation (23.5%, 35.4%, 46.3%, and 61.5% for the low-, borderline-, intermediate, and high-risk groups, respectively). The total explanatory variation was 61.9% for 2 principal variation factors (baPWV, 36.8% and creatinine, 25.1%). The vascular age predicted using baPWV greatly exceeded the chronological age. Plaque formation was significant even in the low-risk group, and its frequency increased with the predicted ASCVD risk. Risk indicators and baPWV are useful predictors of ASCVD, which in conjunction with conventional pharmacotherapy could be useful for primary prevention of plaque formation in subjects with cardiovascular comorbidities.