ABSTRACT
BACKGROUND: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. METHODS: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. DISCUSSION: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03309683 . Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.
Subject(s)
Colonic Polyps , Endoscopic Mucosal Resection , Colon/surgery , Colonic Polyps/surgery , Colonoscopy , Endoscopic Mucosal Resection/adverse effects , Humans , Multicenter Studies as Topic , Netherlands , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/prevention & control , Randomized Controlled Trials as Topic , Surgical InstrumentsABSTRACT
BACKGROUND: Patients with renal insufficiency have an increased risk of cardiovascular disease that is not fully explained by the presence of known cardiovascular risk factors. In patients with end-stage renal disease, increased serum concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), has been linked to excess cardiovascular morbidity. We investigated, in patients with mild-to-moderate renal failure, the relationship between plasma ADMA and three surrogate markers of atherosclerosis that have been shown to have prognostic value, namely carotid intima-media thickness (IMT), plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasma C-reactive protein (CRP). METHODS: We used baseline data of an ongoing randomized trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic nondiabetic renal failure without clinical evidence of atherosclerosis (GFR 15 to 70 mL/min/per 1.73 m(2) according to the Cockcroft-Gault equation; ATIC study). RESULTS: Data from 93 patients were used. Creatinine clearance was inversely related to plasma ADMA concentration (standardized beta after adjustment = -0.342, P = 0.023). Plasma ADMA was strongly related to carotid IMT in univariate (beta = 0.459, P < 0.0001) and multivariate analysis (beta= 0.444, P < 0.0001). Plasma ADMA was also significantly related with plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) in univariate (beta = 0.260, P = 0.010) and multivariate (beta = 0.242, P = 0.022) analysis. Plasma ADMA was not significantly related to C-reactive protein (beta = -0.134, P = 0.204). CONCLUSION: In patients with mild-to-moderate renal failure, renal function is inversely associated with plasma ADMA, which, in turn, is positively associated with carotid IMT and plasma sVCAM-1 concentration. Increased plasma ADMA may be a link between renal function and cardiovascular disease in patients with mild-to-moderate renal failure.
