Endoscopic submucosal dissection for colorectal neoplasia: outcomes and predictors of recurrence.

Background and study aims The role of endoscopic submucosal dissection (ESD) for colorectal lesions in Western communities is unclear and its adoption is still limited. The aim of this study is to assess the long-term outcomes of a large cohort of patients treated with colorectal ESD in a tertiary Western center. Patients and methods A retrospective analysis was conducted on patients treated by ESD for superficial colorectal lesions between February 2011 and November 2019. The primary outcome was the recurrence rate. Secondary outcomes were en-bloc and R0 resection rates, procedural time, adverse events (AEs), and need for surgery. The curative resection rate was assessed for submucosal invasive lesions. Results A total of 327 consecutive patients, median age 69 years (IQR 60-76); 201 men (61.5 %) were included in the analysis. Of the lesions, 90.8 % were resected in an en-bloc fashion. The rate of R0 resection was 83.1 % (217/261) and 44.0 % (29/66) for standard and hybrid ESD techniques, respectively. Submucosal invasion and piecemeal resection independently predicted R1 resections. A total of 18(5.5 %) intra-procedural AEs (perforation:11, bleeding:7) and 12(3.7 %) post-procedural AEs occurred (perforation:2, bleeding: 10). Eighteen adenoma recurrences per 1,000 person-years (15cases, 5.6 %) were detected after a median follow-up time of 36 months. All recurrences were detected within 12 months. No carcinoma recurrences were observed. R1 resection status and intra-procedural AEs independently predicted recurrences with seven vs 150 recurrences per 1,000 person-years in the R0 vs R1 group, respectively. Conclusions Colorectal ESD is a safe and effective option for managing superficial colorectal neoplasia in a Western setting, with short and long-terms outcomes comparable to Eastern studies. En-bloc R0 resection and absence of intra-procedural AEs are associated with reduced risk of recurrence.

Submucosal tunnelling techniques for Zenker's diverticulum: a systematic review of early outcomes with pooled analysis.

In the last decade, flexible endoscopic septotomy has been reported as a well-tolerated and effective treatment for Zenker's diverticulum. More recently, novel endoscopic submucosal tunneling techniques, namely Zenker-PerOral Endoscopic Myotomy (Z-POEM) and PerOral Endoscopic Septotomy (POES) have been proposed to obtain complete muscular septum exposure and deeper myotomy. The aim of this study is to provide a systematic review with a meta-analysis of the first experiences of third space approaches for Zenker's diverticulum. Electronic databases (Medline, Scopus, EMBASE) were searched up to October 2020. Studies including patients with symptomatic Zenker's diverticulum who underwent endoscopic treatment by submucosal tunneling technique were eligible. Procedural, clinical and safety outcomes were assessed by pooling data with a random-effect model to obtain a proportion with a 95% confidence interval. Nine retrospective studies were eligible for inclusion (196 patients). Five studies were performed in the USA, two in Europe and two in Asia. Endoscopic treatment was feasible in 96.9% (I2 = 0%) of patients. The mean procedure duration was 36.4 ± 14.3 minutes. Clinical success was achieved after 93.4% (I2 = 0%) of procedures. The overall adverse events rate was 4.9% (I2 = 0%). No differences between the two approaches (Z-POEM vs POES) have been shown in terms of both efficacy and safety. Submucosal tunneling techniques appear to be feasible for symptomatic Zenker's diverticulum, with promising results in terms of efficacy and safety outcomes.

Safety and efficacy of multiband mucosectomy for Barrett's esophagus: a systematic review with pooled analysis.

BACKGROUND: According to guidelines, all visible lesions in Barrett's esophagus (BE) should be endoscopically resected. Available methods of endoscopic resection include the cap-assisted technique and, more recently, multiband mucosectomy (MBM). Data on the efficacy and safety of MBM have yet to be systematically reviewed. We performed the first systematic review with pooled analysis to evaluate the outcomes of MBM in patients with BE. METHODS: Electronic databases (Medline, Scopus, EMBASE) were searched up to August 2019. Studies including patients with BE who underwent MBM were eligible. The primary outcome was the adverse events rate. Secondary outcomes were the proportions of complete resections and R0 resections. Outcomes were assessed by pooling data using a random or fixed-effect model, according to the degree of heterogeneity, to obtain a proportion with a 95% confidence interval. RESULTS: Fourteen studies were eligible (1334 procedures, 986 patients). The adverse event rate was 5.3%. Immediate and post-procedural bleeding, perforations and strictures occurred in 0.2%, 0.7%, 0.3% and 3.9% of procedures, respectively. Focal lesions were resected at a complete rate of 97.6% with an R0 resection rate of 94.1%. CONCLUSION: MBM is a safe and effective technique for treating visible lesions in BE.

Artificial intelligence technologies for the detection of colorectal lesions: The future is now.

Several studies have shown a significant adenoma miss rate up to 35% during screening colonoscopy, especially in patients with diminutive adenomas. The use of artificial intelligence (AI) in colonoscopy has been gaining popularity by helping endoscopists in polyp detection, with the aim to increase their adenoma detection rate (ADR) and polyp detection rate (PDR) in order to reduce the incidence of interval cancers. The efficacy of deep convolutional neural network (DCNN)-based AI system for polyp detection has been trained and tested in ex vivo settings such as colonoscopy still images or videos. Recent trials have evaluated the real-time efficacy of DCNN-based systems showing promising results in term of improved ADR and PDR. In this review we reported data from the preliminary ex vivo experiences and summarized the results of the initial randomized controlled trials.

Multi-band mucosectomy for neoplasia in patients with Barrett's esophagus: in vivo comparison between two different devices.

BACKGROUND: Multi-band mucosectomy (MBM) is effective and safe for Barrett's neoplasia. No studies have yet compared the efficacy and safety of the MBM devices commercially available: Duette™ (CookMedical) and Captivator™ (BostonScientific). Our aim is to compare the two devices. METHODS: This is a dual-center retrospective case-control study (Rozzano, Portsmouth) comparing efficacy, safety, and histology of resected specimens between Duette™ (DUE) and Captivator™ (CAPT). Efficacy was assessed by R0 and local recurrence (LR) rate. Bleedings, perforations, and strictures were recorded as safety outcomes. Moreover, the specimens were re-examined by two pathologists, blinded about the study group, to assess the maximum thickness of both the whole specimens and the resected submucosal layer. RESULTS: Seventy-six patients (38 per group) were included. The two groups did not differ in terms of baseline characteristics. R0 resection was achieved in 96.7% versus 96.3% (p = ns) and LR were recorded in 4/38 (10.5%) versus 3/38 (7.9%) in DUE and CAPT group, respectively (p = ns). Considering Duette™ versus Captivator™, 2 versus 3 patients developed a symptomatic stricture. Only one post-procedural bleeding occurred (Captivator™). Maximum medium thicknesses of specimens and of resected submucosa did not differ between the groups. CONCLUSIONS: MBM is safe and effective for resecting visible lesions using either of the two available devices.

Clinical outcomes with long-term sorafenib treatment of patients with hepatocellular carcinoma: a multicenter real-life study.

AIM: This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients. METHODS: Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months. RESULTS: Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9-44.3). Only baseline Child-Pugh class was associated with survival. CONCLUSION: Sorafenib could result in long-term control of HCC in a relevant proportion of patients. Given the availability of regorafenib in the second-line setting, an earlier introduction of systemic therapy may be considered according to clinical indications.

Report from European Association for the Study of the Liver: HCC Summit, Geneva, Switzerland, 2-5 February 2017.

The European Association for the Study of the Liver Hepatocellular Carcinoma (HCC) international meeting held in Geneva in February 2017 focused on the state of the art of HCC management, from diagnosis to treatment and the potential development of clinical research in this field. This report reviews some of the most interesting topics discussed at the meeting such as the role of hepatitis C viral infection treatment with direct-acting antivirals in enhancing HCC risk, current prognostic systems, early diagnosis techniques, curative therapies for early HCC and the systemic treatments for advanced disease with a look into future perspectives.

Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma.

BACKGROUND & AIMS: Assessment of long-term outcome is required in hepatitis C virus (HCV)-infected patients with cirrhosis, who have been successfully treated for Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC). However, problems arise due to the lack of models accounting for early changes during follow-up. The aim of this study was to estimate the impact of early events (HCC recurrence or hepatic decompensation within 12months of complete radiological response) on 5-year overall survival (OS) in a large cohort of patients with HCV and cirrhosis, successfully treated HCC. METHODS: A total of 328 consecutive Caucasian patients with HCV-related cirrhosis and BCLC stage 0/A HCC who had complete radiological response after curative resection or thermal ablation were prospectively recruited to this study. Primary endpoint of the study was 5-year OS. Independent baseline and time-dependent predictors of 5-year OS were identified by Cox model. RESULTS: The observed 5-year survival rate was 44%. The observed HCC early recurrence and early hepatic decompensation rate were 21% and 10%, respectively. Early hepatic decompensation (Hazard Ratio [HR] 7.52; 95% confidence intervals (CI): 1.23-13.48) and HCC early recurrence as time-dependent covariates (HR 2.50; 95%CI: 1.23-5.05), presence of esophageal varices at baseline (HR 1.66; 95% CI: 1.02-2.70) and age (HR 1.04; 95% CI: 1.02-1.07) were significantly associated with the 5-year OS. CONCLUSION: Survival in HCV-infected patients with cirrhosis and successfully treated HCC is influenced by early hepatic decompensation. Our study indirectly suggests that direct-acting antiviral agents could improve OS of HCC patients through long-term preservation of liver function, resulting in a lower cirrhosis-related mortality and a greater change of receiving curative treatments. LAY SUMMARY: Survival in hepatitis C virus (HCV) infected patients with cirrhosis and successfully treated hepatocellular carcinoma (HCC), is mainly influenced by early hepatic decompensation. HCV eradication after treatment with new direct-acting antiviral agents could improve overall survival of HCC patients through long-term preservation of liver function.

Efficacy and safety of endoscopic papillary balloon dilation for the removal of bile duct stones: Data from a "real-life" multicenter study on Dilation-Assisted Stone Extraction.

AIM: To report data on Dilation-Assisted Stone Extraction (DASE) use in clinical practice and its efficacy and safety trough three Italian referral centers for biliopancreatic diseases treatment. METHODS: From January 2011 to December 2015 we collected data on 120 patients treated with DASE. Technical success was obtained when the endoscopist was able to place the balloon trough the papilla inflating the balloon until the final diameter for an adequate time (at least 30 s). Clinical success was obtained after complete stone removal (no remaining stones were visible at the cholangiogram). RESULTS: Forty-nine male (40.8%) and 71 female (59%) were enrolled. The mean age was 67.8 years ± 15.7. The mean common bile duct (CBD) dilation was 19.2 mm ± 3.9 and the mean size of stones 15.8 ± 2.9. DASE was applied as first approach in 38% (62% after initial failure of stones extraction). Technical and clinical success was of 91% and 87% respectively. In those in which DASE failed alternative treatment were adopted. After DASE 18% of patients experienced a complication (bleeding 9%, pancreatitis 8%, perforation 0.8%). At univariable analysis, elective endoscopic retrograde cholangiopancreatography (P = 0.031), DASE as first approach (P = 0.032), and cannulation of major papilla followed by guidewire insertion (P = 0.004) were related to low risk of complications. Pre-cut was related to an increased risk of complications (P = 0.01). CONCLUSION: DASE allowed a higher first-session success rate and can be consider a valid alternative to endoscopic sphincterotomy not only for bigger CBD stones.

Refining prognosis after trans-arterial chemo-embolization for hepatocellular carcinoma.

BACKGROUND & AIMS: To develop an individual prognostic calculator for patients with unresectable hepatocellular carcinoma (HCC) undergoing trans-arterial chemo-embolization (TACE). METHODS: Data from two prospective databases, regarding 361 patients who received TACE as first-line therapy (2000-2012), were reviewed in order to refine available prognostic tools and to develop a continuous individual web-based prognostic calculator. Patients with neoplastic portal vein invasion were excluded from the analysis. The model was built following a bootstrap resampling procedure aimed at identifying prognostic predictors and by carrying out a 10-fold cross-validation for accuracy assessment by means of Harrell's c-statistic. RESULTS: Number of tumours, serum albumin, serum total bilirubin, alpha-foetoprotein and maximum tumour size were selected as predictors of mortality following TACE with the bootstrap resampling technique. In the 10-fold cross-validation cohort, the model showed a Harrell's c-statistic of 0.649 (95% CI: 0.610-0.688), significantly higher than that of the Hepatoma Arterial-embolization Prognostic (HAP) score (0.589; 95% CI: 0.552-0.626; P = 0.001) and of the modified HAP-II score (0.611; 95% CI: 0.572-0.650; P = 0.005). Akaike's information criterion for the model was 2520; for the mHAP-II it was 2544 and for the HAP score it was 2554. A web-based calculator was developed for quick consultation at http://www.livercancer.eu/mhap3.html. CONCLUSIONS: The proposed individual prognostic model can provide an accurate prognostic prediction for each patient with unresectable HCC following treatment with TACE without class stratification. The availability of an online calculator can help physicians in daily clinical practice.

Metabolic factors and chronic hepatitis C: a complex interplay.

In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we focus on the pathophysiological mechanisms underlying the correlation between HCV infection and metabolic disorders, the impact of metabolic factors on the progression of liver and non-liver-related diseases, and, on the contrary, the possible influence of chronic HCV infection on metabolic features. In this setting, the importance of a multifaceted evaluation of CHC patients and a prompt correction of modifiable metabolic risk factors should be emphasized.

Survival of patients with hepatocellular carcinoma (HCC) treated by percutaneous radio-frequency ablation (RFA) is affected by complete radiological response.

BACKGROUND: Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. AIM: To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. METHODS: A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. RESULTS: The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR. The proportion of major complications after treatment was 4%. CONCLUSIONS: RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival.