Factors predicting long-term outcomes of early-stage hepatocellular carcinoma after primary curative treatment: the role of surgical or nonsurgical methods.

BACKGROUND: We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. METHODS: Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. RESULTS: One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01-2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26-3.08), early recurrence (HR = 6.62, 95% CI:3.79-11.6) and late recurrence (HR = 3.75, 95% CI:1.99-7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. CONCLUSION: Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

Gender Difference in the Association Between Metabolic Factors and Hepatocellular Carcinoma.

BACKGROUND: A gender difference in hepatocellular carcinoma (HCC) that men have higher incidence than women has long been noted and can be explained by the cross-talk between sex hormones and hepatitis B virus/hepatitis C virus (HBV/HCV). Whether metabolic factors yield similar sexual difference in non-HBV/HCV-HCC remains elusive. METHODS: There were 74 782 hepatitis B surface antigen (HBsAg)/antibody to hepatitis C virus (anti-HCV) negative residents who participated in the Keelung Community-Based Integrated Screening program and were followed in 2000-2007. Incident HCC was identified by linkage to the Taiwan Cancer Registry. Cox proportional hazards regression models were used to estimate the association between metabolic factors and HCC stratified by sex. All statistical tests were 2-sided. RESULTS: With 320 829 follow-up person-years, 99 residents developed HCC. The adjusted hazard ratios (aHR) were 2.10 (95% confidence interval [CI] = 1.07 to 4.13) and 3.71 (95% CI = 2.01 to 6.86) for prediabetes and diabetes, respectively, in men. The corresponding adjusted hazard ratios were 1.16 (95% CI = 0.48 to 2.83) and 1.47 (95% CI = 0.65 to 3.34) in women. Compared with normal weight (body mass index [BMI] = 23-25), underweight (BMI < 21, HR = 3.56, 95% CI = 1.18 to 10.8) and overweight (BMI = 25 to <27.3, HR = 3.81, 95% CI = 1.43 to 10.2) were associated with an elevated risk in men. The statistically significant gradient relationship per advanced BMI category was noted in women (aHR = 1.41, 95% CI = 1.07 to 1.87). The HCC-fasting glucose (P = .046) and HCC-BMI (P = .03) associations were statistically significantly modified by sex. Elevated aspartate aminotransferase, aspartate aminotransferase-to-platelet index and fibrosis index, and habitual alcohol consumption were related to HCC only in men, whereas increased alanine aminotransferase and lower platelet levels predicted HCC risk in women. CONCLUSIONS: We found that BMI-HCC associations were U-shape for men and linear for women, and the elevated HCC risk began from glucose impairment in men only. Whether good glycemic and weight control can reduce HCC risk warrants further investigation.

Consolidation period of 18 months no better at promoting off-treatment durability in HBeAg-positive chronic hepatitis B patients with tenofovir disoproxil fumarate treatment than a 12-month period: A prospective randomized cohort study.

There has been no clear consensus on the optimal consolidation periods following HBeAg seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients. Our study aimed to prospectively compare relapse rates between 12 months' and 18 months' consolidation periods to see whether or not there is beneficial durability of tenofovir disoproxil fumarate (TDF) therapy with longer consolidation periods.We enrolled a total of 137 HBeAg-positive Asian CHB patients treated with TDF monotherapy. Forty-six patients achieved HBeAg SC. Then, they were randomly assigned to consolidation period of either 12 months (group A) or 18 months (group B). After stopping TDF therapy, all patients were followed up for 12 months.Thirteen patients (56.5%) relapsed in group A and 12 patients (52.2%) relapsed in group B after 12 months' follow-up (P = .958). Pretreatment HBsAg level is the only significant predictor for off-therapy recurrence by univariate analysis (P = .024). Baseline HBeAg >1000 S/CO in group B patients were significantly less likely to relapse than those of group A (P = .046). Baseline alanine aminotransferase (ALT) >133 U/L could significantly predict occurrence of HBeAg SC (P = .008; 95% CI: 0.545-0.763; AUC: 0.654).Overall, a prolonged consolidation period has no positive effect on TDF therapy on sustained viral suppression in HBeAg-positive Asian CHB patients. However, a prolonged consolidation period was beneficial to patients with high baseline semi-quantitative HBeAg levels in terms of off-treatment durability. Baseline ALT > 133 U/L could significantly predict the occurrence of HBeAg SC.

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening.

AIM: To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening. CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval.

Diffuse esophageal leiomyomatosis with a pedunculated polyp.

Although leiomyomas are the most common benign tumors of the esophagus, esophageal leiomyomatosis is a rare pathological entity, and pedunculated presentation is even rarer. A 61-year-old man was found, incidentally, to have an esophageal tumor on a survey of chest computed tomography (CT) examination for a pulmonary nodule. Endoscopy disclosed a pedunculated polyp covered by nearly normal esophageal mucosa, with surrounding annular extension of a submucosal elevation. Endoscopic ultrasonography (EUS) revealed a hypoechoic tumor, with a maximum diameter of 3 cm originating from the thickened muscularis mucosa layer. The underlying muscularis propria layer was also prominently thickened. The polypoid lesion was then removed by endoscopic resection with wire-loop ligation, followed by snare electrocoagulation. The pathological diagnoses of the polyp and the surrounding submucosal lesions were both leiomyoma. Diffuse esophageal leiomyomatosis was suspected in this situation because of the characteristic pathological distribution. In this patient, the EUS findings corresponded well to the characteristic features of diffuse esophageal leiomyomatosis noted in previous reports, and this was of great help for the diagnosis, in addition to the endoscopic findings. This case report is presented with a particular focus on the problems associated with accurate diagnosis.