Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial.

OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).

Comparative analysis of ESD versus EMR in a large European series of non-ampullary superficial duodenal tumors.

BACKGROUND AND STUDY AIMS: The choice of endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) in non-ampullary superficial duodenal tumors (NASDTs) is challenging and the benefits of ESD remain unclear. The aim was to comparatively analyze the feasibility, outcomes and safety of these techniques in these lesions. PATIENTS AND METHODS: This is an observational and retrospective study. All consecutive patients presenting with NASDTs who underwent EMR or ESD between 2005 and 2017 were included. The following main outcomes were comparatively evaluated: en-bloc and complete (R0) resection rates, and local recurrence. Secondary outcomes were perforation and delayed bleeding. RESULTS: One hundred sixty-six tumors in 150 patients (age: 66 years, range: 31 - 83, 42.7 % males) were resected by ESD (n = 37) or EMR (n = 129) and included. The median procedure time (81 vs. 50 min, P  = 0.007) and tumor size (25 vs. 20 mm, P  = 0.01) were higher in the ESD group. The global malignancy rate was 50.3 %. There were no differences in en-bloc resection (29.7 % vs. 44.2 %, P  = 0.115), complete resection (19.4 % vs. 35.5 %, P  = 0.069), and local recurrence (14.7 % vs. 16.7 %, P  = 0.788) rates. Tumor size was associated with recurrence (28 vs. 20 mm, P  = 0.008), with a median follow-up of 6.5 months. Focal recurrence (n = 22, 13.3 %) was treated endoscopically in 86.4 %. En-bloc resection in the ESD group was comparable in large ( ≥ 20 mm) and small lesions (27.6 % vs. 37.5 %, P  = 0.587), while this outcome decreased significantly in large lesions resected by EMR (17.4 % vs. 75 %, P  < 0.001). Nine perforations were confirmed in 6 lesions (16.2 %) resected by ESD and 3 (2.3 %) by EMR ( P  = 0.001). Endoscopic therapy was successful in all but 1 patient (88.9 %) presenting with a delayed perforation. CONCLUSIONS: ESD may be an alternative to EMR and surgery in selected NASDTs, such as large duodenal tumors where EMR achieves low en-bloc resection rates and the local recurrence may be higher. However, this technique may have a higher risk of perforations.

ESD versus EMR in non-ampullary superficial duodenal tumors: a systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has been developed as an option for treatment of esophageal, gastric and colorectal lesions. However, there is no consensus on the role of ESD in duodenal tumors. METHODS: This systematic review and meta-analysis compared ESD and endoscopic mucosal resection (EMR) in sporadic non-ampullary superficial duodenal tumors (NASDTs), including local experience. We conducted a search in PubMed, Scopus and the Cochrane library up to August 2017 to identify studies that compared both techniques reporting at least one main outcome (en-bloc/complete resection, local recurrence). Pooled outcomes were calculated under fixed and random-effect models. Subgroup analyses were conducted. RESULTS: A total of 753 patients presenting with 784 NASDTs (242 ESD, 542 EMR) in 14 studies were included. Tumor size (MD: 5.88, [CI95 %: 2.15, 9.62], P  = 0.002, I 2  = 79 %) and procedure time (MD: 65.65, [CI95 %: 40.39, 90.92], P  < 0.00001, I 2  = 88 %) were greater in the ESD group. En-bloc resection rate was significantly higher in Asian studies (OR: 2.16 [CI95 %: 1.15, 4.08], P  = 0.02, I 2 : 46 %). ESD provided a higher complete resection rate (OR: 1.63 [I95 %: 1.06, 2.50], P  = 0.03, I 2 : 59 %), but there was no risk difference in the risk of local recurrence (RD: - 0.03 [CI95 %: - 0.07, 0.01], P  = 0.15, I 2 : 0 %) or delayed bleeding. ESD was associated with an increased number of intraoperative perforations [RD: 0.12 (CI95 %: 0.04, 0.20), P  = 0.002, I 2 : 56 %] and emergency surgery for delayed perforations. The inclusion of eligible studies was limited to retrospective series with inequalities in comparative groups. CONCLUSIONS: Duodenal ESD for NASDTs may achieve higher en-bloc and complete resections at the expense of a greater perforation rate compared to EMR. The impact on local recurrence remains uncertain.