Hybrid-APC Margin Ablation to Prevent Post EMR Adenoma Recurrence

Study Overview
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Brief Summary
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Endoscopic Mucosal Resection (EMR) is the current standard for effective endoscopic resection of such colon adenomas. If resection is possible in one piece (so-called en bloc resection) then recurrence rates are low. However, most non-pedunculated polyps >2 cm are removed in pieces (piece-meal resection) which leads to disease recurrence rates between 12-30%. In the March 2019 issue of Gastroenterology Bourke et al. presented that post-EMR ablation of the resection margins using soft coagulation with the tip of a resection snare reduces adenoma recurrence to 5% compared to 21% recurrence found in the control group. Hybrid Argon Plasma Coagulation (h-APC) combines an ablation technique (APC) with the option for submucosal saline injection using a high-pressure water jet. The technique allows to lift of dysplastic epithelium thus creating a safety cushion under the mucosa is lifted with a saline injection and then to ablate larger areas more thoroughly and with a higher energy setting, with a low risk for side effects or complications.

Detailed Description
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Our study hypothesis is that routine use of hybrid Argon Plasma Coagulation (h-APC) for ablation of the post-EMR resection margins and resection surface area will reduce post-EMR adenoma recurrence to 5% or lower. This is a prospective, multi-center study enrolling patients with non-pedunculated colorectal polyps ≥ 20mm for endoscopic mucosal resection (EMR). All primary EMR procedures will combine EMR with h-APC ablation of the base and margins after complete EMR resection to prevent adenoma recurrence. Schedule of activities Enrollment visit before the endoscopy (ALL PATIENTS), in the outpatient clinic, or before the EMR. Eligible patients who have consented to participate in the study will be asked to take a standard colonoscopy preparation before their scheduled procedure. EMR intervention (ALL PATIENTS meeting eligibility criteria). Only if a polyp meets inclusion criteria, the study subject will be enrolled. The standard endoscopic mucosal resection (EMR) technique will be used for the primary removal of all polyps. Submucosal injection will be used to lift the polyp from the muscularis propria. Injection is used as per the current standard of care using a contrast agent and a lifting agent (e.g., NaCl 0.9% or Voluven). Snare electrocautery resection will be facilitated until complete visible removal of the complete polyp. Electrocautery snare technique is facilitated using standard microprocessor-controlled electrocautery. If residual polyp tissue cannot remove by a snare, other means such as cold snare (i.e., for small residual polyp tissue that cannot be engaged into standard snares), hot avulsion technique or Argon plasma coagulation or soft coagulation by the tip of snare can be used. The polyp site will be marked with submucosal injection of approximately 1-2cc of India ink (standard of care to mark lesions in the colon safely) to allow recognition at follow-up endoscopy. Polyps are sent to the pathology lab and evaluated according to standard practice by institutional pathologists.19 To determine the homogeneity and depth of h-APC margin ablation in the pathology lab, some ablated margins might be resected using the standard cold snare technique. Telephone calls or visits 14-30 days following the EMR will be conducted to assess possible adverse events. Follow-up 1 (FU1, ALL PATIENTS): colonoscopy 4 months (± 2 months) after the EMR intervention with the assessment of the primary outcome (biopsy/pathology-confirmed recurrence at post-EMR site). Patients with visible recurrence at the EMR site will undergo additional h-APC treatment for complete eradication at the first follow-up. Follow-up 2 (ONLY FOR PATIENTS with visible recurrence and biopsy confirmed recurrence at FU1 will undergo FU2 scheduled 4 months (± 2 months) after FU1 (within 1 year after EMR procedure) with the assessment of recurrence/complete eradication rates (biopsy/pathology confirmed complete eradication post-EMR and h-APC at FU1). Patients with not visible but pathology-confirmed recurrence will be rescheduled for another colonoscopy with h-APC treatment of the post-EMR site and another follow-up colonoscopy for biopsies and confirmation of complete/incomplete eradication within 1 year after the initial EMR.

Official Title
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Hybrid-APC Margin Ablation to Prevent Post EMR Adenoma Recurrence

Conditions
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Colorectal Cancer, Polyp of Colon

Intervention / Treatment
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* Procedure: Hybrid Argon Plasma Coagulation and EMR procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Ethnicity and race; Patient referred for endoscopic resection of all colorectal polyps non-pedunculated equal or greater 20 mm ; Written informed consent Exclusion Criteria: Patients with known (biopsy proven) invasive carcinoma in a potential study polyp; Previous partial EMR; Pedunculated polyps (as defined by Paris Classification type Ip or Isp); Patients with ulcerated depressed lesions (as defined by Paris Classification type III); Patients with inflammatory bowel disease; Patients who are receiving an emergency colonoscopy; Poor general health (ASA class>3); Patients with coagulopathy with an elevated INR ≥1.5, or platelets <50; Poor bowel preparation (Boston bowel prep score ≤2); Target sign or perforation during initial EMR; Need for ESD for complete resection prior to APC, Pregnancy and breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group treatment h-APC and EMR<br>Standard endoscopic mucosal resection (EMR) technique will be used for primary removal of all polyps. Submucosal injection will be used to lift the polyp from the muscularis propria. Injection is used as per the current standard of care using a contrast agent and a lifting agent (e.g. NaCl 0.9% or Voluven). Snare electrocautery resection will be facilitated until complete visible removal of the complete polyp. Electrocautery snare technique is facilitated using standard microprocessor controlled electrocautery (e.g. ERBE VIO Endocut 3-1-6). Ablation of the margin after visibly complete removal of the polyp is routinely applied. For thermal ablation hybrid APC (Erbe Hybrid APC) will be applied using standard settings on the margin and resection base. Once resection and thermal ablation is considered complete the mucosal defect can be closed with clips or another preventative measure applied to reduce the risk for post-polypectomy bleeding. | Procedure: Hybrid Argon Plasma Coagulation and EMR procedure<br>* Hybrid Argon Plasma Coagulation (h-APC) combines an ablation technique (APC) with the option for submucosal saline injection using a high-pressure water jet. The technique allows to lift dysplastic epithelium thus creating a safety cushion under the mucosa is lifted with a saline injection and then to ablate larger areas more thoroughly and with a higher energy setting, with a low risk for side effects or complications<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate adenoma recurrence rate | The primary aim of the study is to evaluate adenoma recurrence rate after EMR and h-APC margin ablation at the first follow-up colonoscopy. | 3-6 months after the index h-APC and EMR procedure | 
| Evaluate complete adenoma eradication rates | The secondary aims of the study are to evaluate complete adenoma eradication rates within 1 year after the index EMR when using EMR with margin ablation and ablating all recurrence found at the first follow up colonoscopy with h-APC. | Within 1 year after the inder EMR | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completeness of thermal ablation of polyp resection margin | Completeness of thermal ablation of polyp resection margin defined as the proportion of margins with at least one region of unablated margin as determined by histopathological evaluation of resected ablated margins. | 14 days after the index EMR | 
| To evaluate the uniformity of the margins and bases of resection after hAPC ablation following an EMR. | To evaluate the uniformity of the margins and bases of resection after hAPC ablation following an EMR. We will ask one pathologist and two independent endoscopists to rate the uniformity of mucosal destruction, depth of injury, lateral ablation zone in minimum and maximum extent, and mucosal destruction within the ablation zone rim. | 14 days after the index EMR |