Cold EMR Vs Standard EMR for the Treatment of Large Nonpedunculated Homogeneous Colorectal Lesions

Study Overview
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Brief Summary
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This study compares the effectiveness in complete resection (absence of recurrence at 6 months) the two different techniques for performing endoscopic mucosal resection (EMR) of nonpedunculated homogeneous colorectal lesions >20mm

Detailed Description
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Colonoscopy is the reference diagnostic test for the study of colon diseases. This procedure also allows the realization of endoscopic therapeutics techniques; thus, endoscopic mucosal resection (EMR) is an effective and safe therapy for the treatment of premalignant and early malignant colorectal lesions of the colon and its use is universal. Usually, colon lesions larger than 10 mm (or pedunculated of any size) require for resection the use of electrocoagulation current (or hot snare polypectomy) and thus is reflected in the most recent clinical practice guidelines (ESGE guidelines, for example). However, the risk of side adverse effects from the use of electrocoagulation is not insignificant and includes post-polypectomy bleeding, post-polypectomy syndrome, post-polypectomy fever and/or immediate or delayed perforation. This risk of complications is higher depending on the characteristics and size of colorectal lesions resected. On the other hand, currently in small lesions not pedunculated (< 10 mm), it is recommended to use cold snare polypectomy according to ESGE clinical guidelines, as it has been seen in previous studies that this reduces complication rates without varying the effectiveness in resection. However, in lesions > 10 mm the previous experience with cold snare resection is less, probably motivated by the possible drawbacks in terms of the possible difficulty of resection of thick tissue with cold snare and a possible increased intra-procedure hemorrhagic risk that can make it difficult to see the scar, with the possibility of leaving residual tissue. However, in recent years the accumulated evidence gathered in various studies and grouped in a recent systematic review suggests that endoscopic mucosal resection with cold snare (Cold-EMR) may be safer than electrocoagulation resection for both 10-19mm lesions and for lesions >20 mm, associated with a lower rate of adverse effects with similar efficacy rates in terms of complete resection and adenomatous recurrence rate. Still, evidence for the treatment of nonpedunculated lesions >20 mm is relatively limited and is not based on randomized comparative studies with the standard EMR technique.

Official Title
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Cold EMR Vs Standard EMR for the Treatment of Large Nonpedunculated Homogeneous Colorectal Lesions.Randomized and Multicentric Clinical Trial

Conditions
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Adenoma Colon, Serrated Polyp, Serrated Adenoma, Colorectal Neoplasms

Intervention / Treatment
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* Procedure: Standard Endoscopic Mucosal Resection
* Procedure: Cold Snare Endoscopic Mucosal Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of age > 18 years undergoing a colonoscopy for any reason of request and who do not meet exclusion criteria. Nonpedunculated homogeneous colorectal lesions type LST ( Paris 0-IIa morphology) and serrated lesions larger than 20 mm without endoscopic data of malignancy: NICE 1 pattern +/- NICE 2 component ( serrated lesions) or NICE2 pattern/JNET 2A (adenomas) and therefore subsidiaries of RME. Randomization will be performed per patient, not for colorectal lesions Signature of informed consent of endoscopic exploration Exclusion Criteria: .No signature of informed consent prior to the study procedure. Absence of proper suspension of the anticoagulant/antiplatelet therapy prior to procedure according to usual pre-procedure recommendations (BSG and ESGE guidelines) Patients with severe thrombopenia/ coagulopathy (Platelets < 50,000/INR > 1.5) not corrected prior to procedure (plasma or platelet transfusion) Patients not candidates for endoscopic resection of colorectal lesions by comorbidities. Pregnant. Patients with inflammatory bowel disease (IBD) Urgent colonoscopy. Poor preparation (BBPS <2 in the colon segment where the lesion is located) Laterally spreading tumors (LST) lesions with non-homogeneous morphology including: sessile polyps (0-Is), pedunculated (0-Ip) and LST lesions with depressed or excavated components (Paris 0-IIc or Paris 0-III), LST granular nodular mixed, LST-G with whole nodular type. In case of doubt depressed component (Paris 0-IIc) or histological borderline lesion (JNET2B), will be excluded from the study. Histological prediction of deep invasive or non-subsidiary to endoscopic mucosal resection lesion as a treatment of choice: NICE 3 pattern by inspection with NBI or Kudo V pattern in traditional/electronic chromoendoscopy or Sano IIIA/IIIB pattern Endoscopic resection of post-EMR scar level relapses

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective randomized study (1:1), multicenter, non-blind of consecutive non-pedunculated lesions of serrated and adenomatous histology, homogeneous, with a size greater than or equal to 20 mm (no upper limit in size). Performing cold-EMR vs standard EMR. A non-inferiority study of cold-EMR versus standard EMR.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Endoscopic Mucosal Resection<br>Standard Endoscopic Mucosal Resection, if necessary, multi-piece to resect large nonpedunculated homogeneous colorectal lesions (>20 mm) | Procedure: Standard Endoscopic Mucosal Resection<br>* Use of injected colloidal or saline solution to raise a lesion prior to polypectomy snare closed over a polyp with electrocautery<br>* Other names: Standard EMR;|
| Experimental: Cold Snare Endoscopic Mucosal Resection<br>Cold Snare Endoscopic Mucosal Resection, if necessary, multi-piece to resect large nonpedunculated homogeneous colorectal lesions (>20 mm) | Procedure: Cold Snare Endoscopic Mucosal Resection<br>* Use of injected colloidal or saline solution to raise a lesion prior to polypectomy snare closed over a polyp without electrocautery<br>* Other names: Cold EMR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete resection of the lesion | Complete resection of the lesion is defined as the non-visualization by the endoscopist of a residual lesion in the mucosal defect and its edge at the end of the EMR and no visualization of recurrence in the post-EMR scar on the first surveillance colonoscopy and absence of recurrence data in scar biopsies | 3-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Security profile | Security profile is defined as the observed percentage of complications (Intra-procedure bleeding, deferred bleeding, deferred bleeding in antiplatelet and/or anticoagulated patients,post-polypectomy fever, post-polypectomy syndrome, deep muscle damage and perforation) in each of the evaluated techniques. | 30 days | 
| Late adenoma recurrence rate | Late adenoma recurrence rate as determined by endoscopic assessment (no visible recurrent adenoma) and histological assessment (scar biopsies) in surveillance colonoscopy at 18 months of the procedure | 18 months | 
| Number of fragments needed to complete the resection | Number of fragments needed to resect with polypectomy snare to complete the resection of the colorectal lesion. | 1 day | 
| Resection time | Time needed to perform endoscopic mucosal resection measured from first snare positioning until complete resection is achieved based on endoscopic assessment. | 1 day | 
| Bloc resection rate | Number of lesions that have undergone resection in a single fragment with each of these evaluated techniques. | 1 | 
| R0 resection rate | Number of lesions with complete macroscopic resection with a negative microscopic margin in the mucosectomy specimen | 1 day | 
| EMR technique conversion rate | Number of lesions to be finally resected with the other arm of study technique not initially assigned | 1 day | 
| Need for additional treatments to complete the resection. | Number of lesions that cannot be completely resected with the assigned EMR technique, requiring different techniques to complete the resection, such as SOFT coagulation with snare tip, APC (argon plasma coagulation), hot avulsion with hot biopsy forceps, biopsy forceps, biopsy forceps +ablation | 1 day | 
| Number of clips used | Number of clip used for hemostatic purposes or for the prophylactic closure of the injury | 1 day | 
| Degree of artifact/interference in the histological interpretation | Subjective impression of the artifact in the histological interpretation of the resected sample (null, moderate, severe) | 1 day | 
| Depth of the resected submucosa | Measure the depth of the resected submucosa layer (in microns) with each of the resection techniques used | 1 day | 
| Percentage of mucosal muscle present in the mucosal protrusions in the resection defect of cold-EMR. | Assess the percentage of presence of mucosal muscle in biopsies performed on the protrusions present in the resection defect of cold-EMR | 1 day | 
| Need for surgery for technical failure | Number of lesions that have to be finally resected by surgery due to technical impossibility for their endoscopic resection. | 6 months | 
| Cost-effectiveness study. | evaluate the cost-effectiveness of each of the endoscopic mucosal resection techniques | 18 months | 
| Sub-analysis by center participating in the study | A subanalysis of the study results by center will be carried out to rule out significant differences between them | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endoscopic mucosal resection, cold snare endoscopic mucosal resection, standard endoscopic mucosal resection, large nonpedunculated homogeneous colorectal lesions, adenoma colon, serrated polyp, serrated adenoma, conventional endoscopic mucosal resection, laterally spreading adenomas.