Background:The methods for preventing post-polypectomy bleeding (PPB) are not standardised and there are groups that use hemoclips for this purpose. Objective: To study whether the use of hemoclips reduces PPB complications. Materials and Methods: Prospective, randomised study of patients with pedunculated polyps larger than 10 mm. The patients were included in two groups (hemoclip before polypectomy -HC-and standard polypectomy -SP-). This study has been registered with the trial registration number NCT01565993. Results: 105 polypectomies were performed (98 patients), 66 (62.9%) in the HC group. The total rate of complications was 10,6% in the HC group (4.5% early bleeding, 1.5% severe delayed bleeding, 4,5% mucosal burns, 1.5% perforation). In the SP group, the rate of total complications was 7,7%, (7,7% early bleeding, no significant differences). In view of the unexpected increase in the morbidity of the hemoclip group, the study was suspended without reaching the sample size. In an ad hoc analysis, which includes the standard polypectomy patients who refused to participate in the study (35 polyps), the total morbidity was 5,7% (no perforations and 2 patients with premature bleeding).When we compared the morbidity of the HC group to the morbidity of SP group plus R group (74 polyps), we also failed to detect any significant differences in terms of PPB, but did in terms of perforation. Conclusion:The prophylactic use of hemoclips in polypectomies of large pedunculated polyps leads to a further risk of mucosal burns and perforation that is not acceptable, and does not reduce the risk of PPB.

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Background & aims: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here we investigate the causal effects of risk factors considered in current GBC prevention programmes as well as C-reactive protein (CRP) level as a marker of chronic inflammation. Approach & results: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (p = 9 × 10-5) and Europeans (p = 9 × 10-5). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (p = 0.03), while higher CRP concentrations increased GBC risk in Europeans (p = 4.1 × 10-6). European results suggest causal effects of BMI on gallstone disease (p = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. Conclusions: Two risk factors considered in the current Chilean programme for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

Background & aims: Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. Most cases of GBC are diagnosed in low-and middle-income countries and research into this disease has long been limited. In this study we therefore investigate the epigenetic changes along the model of GBC carcinogenesis represented by the sequence gallstone disease → dysplasia → GBC in Chile, the country with the highest incidence of GBC worldwide.Approach: To perform epigenome-wide methylation profiling, genomic DNA extracted from sections of FFPE gallbladder tissue was analyzed using Illumina Infinium MethylationEPIC BeadChips. Pre-processed, quality-controlled data from 82 samples (gallstones n=32, lowgrade dysplasia n=13, high-grade dysplasia n=9, GBC n=28) were available to identify differentially methylated markers, regions, and pathways as well as changes in copy number variations (CNVs). Main results:The number and magnitude of epigenetic changes increased with disease development and predominantly involved the hypermethylation of CpG islands and gene promoter regions. The methylation of genes implicated in Wnt signaling, Hedgehog signaling, and tumor suppression increased with tumor grade. CNVs also increased with GBC development and affected CDKN2A, MDM2, TP53, and CCND1. Gains in the targetable ERBB2 were detected in 14% of the GBC samples. Conclusions:Our results indicate that GBC carcinogenesis comprises three main methylation stages: early (gallstone disease and low-grade dysplasia), intermediate (highgrade dysplasia), and late (GBC). The identified gradual changes in methylation and CNVs may help to enhance our understanding of the mechanisms underlying this aggressive disease and eventually lead to improved treatment and early diagnosis of GBC.

Atezolizumab versus the standard of care for the treatment of adult patients with locally advanced or metastatic NSCLC after prior chemotherapy, in Greece. METHODS: A three state partitioned survival model was developed for the costeffectiveness analysis of Atezolizumab vs Docetaxel, Nivolumab and Pembrolizumab. The model was populated with clinical effectiveness data from the literature. Greek-specific data on real-world resource use was sourced from an expert panel of 10 oncologists. Hospital prices were used for all drugs. The analysis followed a third party payer perspective. RESULTS: Atezolizumab offers incremental gains compared to Docetaxel (0.84 LY and 0.59 QALYs), Nivolumab (0.06 LY and 0.01 QALYs) and Pembrolizumab (0.09 LY and 0.06 QALYs). Additional total costs of V43,465 and V810 are introduced with Atezolizumab compared to Docetaxel and Pembrolizumab, whereas a reduction of V11,924 in total costs compared to Nivolumab. Atezolizumab can be considered as a cost-effective (dominant) option for the treatment of NSCLC compared to NIvolumab, and results in an ICER of 51,744/LY gained and 73,669/QALY gained compared to Docetaxel and an ICER of 9,000/LY gained and 13,500/QALY gained compared to Pembrolizumab. CONCLUSIONS: The results of the analysis suggest that the use of anti-PD-L1 Atezolizumab, as 2nd line treatment of NSCLC patients, offers gains in LY and QALY's compared to existing treatment options. Atezolizumab provides health gains either at a lower cost (vs Nivolumab) or at an added cost below the acceptable threshold (vs Docetaxel and Pembrolizumab).

Endoscopic ultrasonography and MRCP are useful techniques in the etiological diagnosis of acute pancreatitis of nonestablished cause. Endoscopic ultrasonography should be preferred for establishing a possible biliary etiology in patients who have not had a cholecystectomy.

Intraoperative ERCP is an option to prevent performing ERCP unnecessarily on patients with moderate risk of CLD not confirmed using appropriate radiological studies. It can resolve the biliary disease in a single step with a similar success rate to standard ERCP, but with low morbidity, especially of acute pancreatitis. The residual CLD rate is also very low.

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