Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Prophylactic clipping after endoscopic mucosal resection of large nonpedunculated colorectal lesions: A meta-analysis.

BACKGROUND AND AIM: It is not clear whether prophylactic clipping after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions (LNPCLs) prevents delayed bleeding (DB). We aimed to conduct a meta-analysis to clarify the efficacy of prophylactic clipping in prevention of DB following EMR of LNPCLs. METHODS: We searched PubMed, EMBASE, Web of Science, ScienceDirect, Cochrane Library databases, and ClinicalTrials.gov for studies that compared clipping versus (vs) nonclipping in prevention of DB following EMR of LNPCLs. Pooled odds ratio (OR) was determined using a random effects model. The pooled ORs of DB, perforation, and post-polypectomy syndrome in the clipping group compared with the nonclipping group comprised the outcomes. Subgroup analyses based on study design, polyp location, and completeness of wound closure were performed. RESULTS: Five studies with a total of 3112 LNPCLs were extracted. Prophylactic clipping reduced the risk of DB compared with nonclipping (3.3% vs 6.2%, OR: 0.494, P = 0.002) following EMR of LNPCLs. In subgroup analysis, prophylactic clipping reduced DB of LNPCLs at proximal location (3.8% vs 9.8%, P = 0.029), but not of them at distal location (P = 0.830). Complete wound closure showed superior efficacy to prevent DB compared with partial closure (2.0% vs 5.4%, P = 0.004). No benefit of clipping for preventing perforation or post-polypectomy syndrome was observed (P = 0.301 and 0.988, respectively). CONCLUSIONS: Prophylactic clipping can reduce DB following EMR of LNPCLs at proximal location. Besides, complete wound closure showed superior efficacy to prevent DB compared with partial closure. Further cost analyses should be conducted to implement the most cost-effective strategies.

The role of albumin-bilirubin grade in determining the outcomes of patients with very early-stage hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and with a single tumor <2 cm in size are classified as having Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC. We aimed to investigate the role of the albumin-bilirubin (ALBI) grade in predicting outcomes in patients with BCLC stage 0 HCC. METHODS: We retrospectively enrolled patients with BCLC stage 0 HCC in Taipei Veterans General Hospital from 2007 to 2015. Prognostic factors were analyzed using a Cox proportional hazards model and propensity score matching (PSM) analysis. RESULTS: There were 420 patients enrolled, including 207 with ALBI grade 1, and 213 with ALBI grade 2 or 3. After a median follow-up of 60.0 months (interquartile range, 37.2-84.6 months), 179 patients died. The cumulative 5-year overall survival (OS) rates were 80.6% in patients with ALBI grade 1 and 53.7% in those with ALBI grade 2 or 3, respectively (p < 0.001). Multivariate analysis showed that age >65 years, negative hepatitis B surface in serum, creatinine >1.0 mg/dL, platelet count ≤105/mm3, tumor size >1.5 cm, nonsurgical resection (SR) therapy, and higher ALBI grade were independent risk factors related to poor OS. Patients who underwent SR had a better OS and recurrence-free survival than those who received radiofrequency ablation, which was confirmed by a multivariate analysis and PSM analysis. CONCLUSION: The ALBI grade can determine OS for patients with BCLC stage 0 HCC. SR can also provide a better outcome than nonsurgical treatment.

Magnifying endoscopy with narrow-band image for diagnosing diffuse type of gastric antral vascular ectasia in cirrhotic patients.

OBJECTIVE: Gastric antral vascular ectasia (GAVE) and portal hypertensive gastropathy (PHG) can cause gastrointestinal bleeding in cirrhotic patients. Distinguishing diffuse-type GAVE and severe PHG is important but difficult by conventional endoscopy and endoscopic biopsy. The aim of this study is to evaluate the value of magnifying endoscopy with narrow-band image for diagnosing diffuse-type GAVE in cirrhotic patients. METHODS: From January 2010 to December 2013, cirrhotic patients with diffuse red spots of stomach in suspicion of diffuse-type GAVE on conventional endoscopy in a tertiary medical center were included. The detection of diffuse red spots on magnifying endoscopy with narrow-band image (NBI) was classified into ring-pattern which suggested GAVE and mosaic-pattern which suggested non-GAVE. The golden diagnosis of GAVE was based on histological criteria of GAVE score ≥3 by any one of two endoscopic sessions. RESULTS: Total 27 cirrhotic patients were included. Twenty-two patients reached the diagnosis of GAVE and five patients were diagnosed of non-GAVE by histology. The diagnostic rate of conventional endoscopy was 81.5% (22/27). The positive rate of initial endoscopic biopsy was 77.2%. On magnifying endoscopy with NBI, the sensitivity, specificity, positive, negative predicted rate and accuracy of ring-pattern for the diagnosis of GAVE were 100, 90, 96.4, 100 and 97.3%. Kappa coefficient of inter-observer agreement for differentiating the ring and mosaic-pattern was 0.92. CONCLUSIONS: The efficacy and accuracy of magnifying endoscopy with NBI for diagnosing diffuse-type GAVE in cirrhotic patients have been demonstrated. It can avoid repeated endoscopy to confirm diagnosis and obviate the invasive biopsy in cirrhotic patients.

The indocyanine green retention test as a noninvasive marker for esophageal varices in patients with hepatocellular carcinoma.

BACKGROUND: The indocyanine green 15-minute retention (ICG-r15) test was considered as a noninvasive marker of esophageal varices (EV) in cirrhotic patients. However, the performance of ICG-r15 in patients with hepatocellular carcinoma (HCC) has rarely been assessed. The aim of this study is to evaluate the value of ICG-r15 as a noninvasive marker of EV in patients with HCC. METHODS: From October 2007 to December 2018, the study retrospectively enrolled 137 HCC patients with compensated hepatic function who received ICG-r15 tests and endoscopy screening for EV. The predictive value of the ICG-r15 test and other noninvasive markers was also evaluated for the diagnosis of EV, including the aspartate aminotransferase (AST)/alanine aminotransferase ratio, platelet count/spleen diameter ratio, AST/platelet ratio index, Lok index, FIB-4, and Park index. RESULTS: In the study cohort, 30 (21.9%) patients had EV. The area under the receiver operating characteristic curve for determining EV by ICG-r15 was 0.784 (95% CI: 0.686-0.881, -2 ln (L): 77.889, Akaike information criterion: 79.889), and it had the best predictive value compared with other noninvasive markers. The cutoff value of ICG-r15 to identify EV was 31.0%, and it had 40.0% sensitivity and 98.1% specificity. The cutoff value to exclude EV was 9.5% with 86.7% sensitivity and 50.5% specificity. In the multivariate analysis, ICG-r15 (odds ratio [OR]: 1.062, 1.014-1.114; p = 0.015) and the Park index (OR: 1.535, 1.091-2.159; p = 0.014) were independently related to the presence of EV. CONCLUSION: ICG-r15 is a practical noninvasive marker with cutoff values of 9.5% for excluding EV and 31.0% for identifying EV in patients with HCC.

Esophageal varices are not predictive of patient prognosis after surgical resection of hepatocellular carcinoma.

OBJECTIVE: The predictive value of esophageal varices (EV) in determining the patient outcome in hepatocellular carcinoma (HCC) remains unresolved. We aimed to assess the impact of EV on the prognosis of HCC patients after surgical resection. MATERIALS AND METHODS: We consecutively enrolled 446 treatment-naive HCC patients who underwent surgical resection and esophagogastroduodenoscopy from 2003 to 2015. Prognostic factors were analyzed using the Cox proportional hazards model and a propensity score matching analysis. RESULTS: A total of 89 (20.0%) HCC patients presented with EV. Compared with those without EV, patients with EV had poorer preservation of liver function and higher rates of cirrhosis in the nontumor part of liver specimens. After a median follow-up period of 34.6 months (25-75 percentiles; 12.8-59.3 months), 130 patients had died. The cumulative 5-year overall survival (OS) rates were 62.3 and 70.6% in patients with and without EV, respectively (P=0.102). A multivariate analysis showed that serum albumin level less than or equal to 4 g/dl (P=0.020), α-fetoprotein level greater than 20 ng/ml (P<0.001), as well as the presence of vascular invasion (P<0.001), but not the presence of EV, were independent risk factors associated with poor OS. Moreover, 67 patients were matched in each group using the one-to-one nearest-neighbor matching method. After matching, the OS rates were comparable between HCC patients with and without EV. CONCLUSION: EV is not an independent risk factor predictive of poor prognosis for HCC patients after resection surgery if they have well-preserved liver function.

Lower serum apelin levels in women with polycystic ovary syndrome.

We tested differences in serum apelin levels between women with polycystic ovary syndrome (PCOS) and those with a healthy regular menstrual cycle, finding that apelin levels were higher in normal women and that apelin was positively correlated with apolipoprotein A levels.