Hybrid Versus Non-Hybrid Endoscopic Submucosal Dissection for Colorectal Polyps (SHORT-ESD)

Study Overview
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Brief Summary
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This proposed trial will randomize 60 patients with a ≥20 mm large colorectal polyp to either undergo hybrid or non-hybrid ESD. For the primary comparison (hybrid vs non-hybrid ESD), the primary outcome will be procedure time. The study will further examine the safety and efficacy of hybrid ESD compared to non-hybrid ESD and investigate factors that may be associated with resection outcomes.

Detailed Description
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Endoscopic submucosal dissection (ESD) permits the en-bloc resection of colorectal lesions irrespective of size. En-bloc resection, as opposed to piecemeal endoscopic mucosal resection (EMR) of colorectal polyps ≥20 mm, provides a more definitive resection specimen for accurate histopathological assessment, and is associated with a low risk for recurrence1,2. Current guidelines from the Japan Gastroenterological Endoscopy Society (JGES), the European Society of Gastrointestinal Endoscopy (ESGE), and the American Gastroenterology Association (AGA), recommend ESD as a preferred strategy for superficial colorectal lesions with suspicion for advanced neoplasia or early cancer (e.g. depressed morphology, advanced surface pattern, nongranular laterally spreading tumor [LST-NG], polyps, ≥20 mm in size)3-5. In these cases, ESD procures an ideal pathological specimen for submucosal staging, provides curative intent, and prevents unnecessary surgery for lesions with low risk for lymph node metastasis6 Yet, ESD in the United States and Europe has been primarily restricted to specialized centers for a variety of reasons, notably due to its technical complexity7. Technical difficulty resides primarily in the process of submucosal dissection using endoknives. Maintaining adequate visualization of the dissection plane during ESD is often regarded the rate-limiting step (Figure 1 Non-hybrid ESD). Other factors, including maintaining the endoknife parallel to the dissection plane and accounting for paradoxical scope movements due to patient-related factors (e.g. colon redundancy, peristalsis, breathing movements) represent formidable challenges during colorectal ESD. These technical hurdles can lead to prolonged procedural times and higher risk for adverse events8. Overcoming these barriers is necessary for the safe and widespread adoption of ESD in Western clinical practice. To reduce the technical difficulty of colorectal ESD, several techniques have been introduced, such as the introduction of traction techniques to assist with the exposure and visualization of the dissection plane during ESD8. However, many of these traction techniques require additional devices, second-hand assistance, and have a learning curve of their own9-12. Hence, many of these methods have not been widely adopted. Hybrid ESD is a modified ESD technique that uses snare-assisted resection as part of the procedure7. With hybrid ESD, a circumferential mucosal incision followed by limited submucosal dissection is performed. Following this, a snare is placed around the lesion, slowly closed to allow resection by traversing the submucosal space. The main advantage of this method is that it reduces the need for deep submucosal dissection underneath the center of the lesion, which intuitively would reduce procedural time and risk of adverse events. Furthermore, snare resection is a technique that is familiar to most endoscopists in the West. A recent systematic review and meta-analysis evaluated outcomes between hybrid ESD and conventional ESD for colorectal lesions7. In aggregate, when compared with conventional ESD among over 2000 patients, hybrid ESD was associated with a shorter procedural time (mean difference of 18.5 minutes, p=0.003). The rate of adverse events decreased for hybrid ESD compared with conventional ESD (odds ratio 1.56; p=0.04), but no difference when stratified by perforation rate (odds ratio 1.86; p=0.11) or delayed bleeding (odds ratio 1.15; p=0.7). Conversely, hybrid ESD was associated with a lower rate of en-bloc resection when compared to conventional ESD (odds ratio 0.31; p<0.001)7. There are several limitations with this data. For one, 14 out of the 16 studies included in this analysis were observational in design. Hence, important factors, such as lesion size, endoscopist experience, type of snare, were not accounted for in most of the studies. Notably, the meta-analysis included studies in which hybrid ESD was used as a rescue therapy after failed conventional ESD, which further complicates the interpretability of the results. Furthermore, only 4 studies originated from the West (Europe) and none from the United States, limiting the generalizability of this technique by US endoscopists. In all, high-quality studies evaluating hybrid ESD for colorectal lesions are needed. This proposed trial will randomize 60 patients with a ≥20 mm large colorectal polyp to either undergo hybrid or non-hybrid ESD. For the primary comparison (hybrid vs non-hybrid ESD), the primary outcome will be procedure time. The study will further examine the safety and efficacy of hybrid ESD compared to non-hybrid ESD and investigate factors that may be associated with resection outcomes. This trial is timely, as ESD has been endorsed in recent years by multiple international and national GI societies. This study will provide information on the feasibility of hybrid ESD as a modified technique that can be more widely adopted in the West. The findings of this trial will therefore help identify a safe and practical ESD technique for large colorectal polyps.

Official Title
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Hybrid Versus Non-Hybrid Endoscopic Submucosal Dissection for Colorectal Polyps: A Randomized Trial (SHORT-ESD)

Conditions
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Colorectal Lesions

Intervention / Treatment
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* Procedure: Hybrid ESD
* Procedure: Non-hybrid ESD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient ≥18 years Ability to provide informed consent Patient scheduled to undergo colonoscopy with endoscopic resection of colorectal polyps Non-pedunculated polyps measuring ≥20 mm in lateral diameter by endoscopic estimation Exclusion Criteria: Age < 18 years Inability to provide informed consent Pedunculated polyps (as defined by Paris classification type Ip)8 Lesions < 20 mm in lateral diameter Suspected adenocarcinoma with deep submucosal invasion (e.g. Paris III morphology, Kudo type Vn pit pattern)4,13 Previously attempted incomplete endoscopic resection (EMR) of the lesion Uncorrected coagulopathy defined as an elevated INR ≥ 1.5 and/or platelet count < 50,000 Any standard contraindication to anesthesia and/or colonoscopy Pregnancy or lactating women

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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No

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: This is a randomized trial where the subject will either be randomized to Hybrid Endoscopic Submucosal Dissection or Non-Hybrid Endoscopic Submucosal Dissection. The provider nor the participant will be aware of what group the subject will be randomized to.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hybrid ESD<br>Hybrid ESD is a modified ESD technique that uses snare-assisted resection as part of the procedure. With hybrid ESD, a circumferential mucosal incision followed by limited submucosal dissection is performed. Following this, a snare is placed around the lesion, slowly closed to allow resection by traversing the submucosal space | Procedure: Hybrid ESD<br>* Method of removing colon lesion<br>* Other names: Endoscopic Mucosal Resection;|
| Active Comparator: Non-Hybrid ESD<br>A partial or complete circumferential mucosal incision will be performed to expose the submucosa around and underneath the polyp. Endoscopic resection will then proceed via conventional ESD, submucosal tunneling or pocket technique. | Procedure: Non-hybrid ESD<br>* Method of removing colon lesion<br>* Other names: Endoscopic Mucosal Resection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • The primary endpoint is to compare procedural time between hybrid vs non-hybrid ESD. | The primary endpoint is to compare procedural time between hybrid vs non-hybrid ESD. Procedure time is defined as the time from the beginning of the submucosal injection to completion of the ESD, defined as complete removal of the polyp from the colonic wall and all interventions for any intraprocedural adverse events. Procedure speed will be calculated by diving the area of the resected specimen by the procedure time (cm2/minute). The following formula will be used to calculate the area: π (3.14) x 0.25 x long axis x short axis/procedure time. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| En-Bloc resection rate | • En-Bloc resection rate: Compare en-bloc resection rate between the two arms (hybrid ESD vs non-hybrid ESD). En-bloc resection is defined as resection of the lesion in one single piece. | 1 day | 
| Completeness of resection | Completeness of resection: defined as removal of all visible polyp tissue at the end of the ESD as assessed by the endoscopist. | 1 day | 
| Complete (R0) resection rate | .Complete (R0) resection rate: Compare complete (R0) resection rate between the two arms (hybrid ESD vs non-hybrid ESD). Complete resection is defined as successful en-bloc resection with histologically negative lateral and deep resection margins. | 1 day | 
| Polyp recurrence | Polyp recurrence: presence of biopsy proven neoplastic polyp tissue at the ESD resection site at SC following complete polyp resection | 6 months | 
| Incidence of overall severe adverse events | • Incidence of overall severe adverse events: aggregate of all severe adverse events that occur at the time of the procedure (immediate complications) or during 30 days of follow-up. Severe adverse events include severe bleeding, perforation, post-polypectomy syndrome, and clinical events that require non-elective hospital admission. | 6 months | 
| Proportion of unremovable polyps | • Proportion of polyps that could not be removed by the assigned treatment, required cross-over to the other arm and/or additional interventions (e.g. use of traction devices, conversion to EMR) | 6 months | 
| ESD technical difficulty: | • ESD technical difficulty: difficulty of the task at hand graded by each endoscopist after each case using the National Aeronautical and Space Administration (NASA) Task Load Index (NASA-TLX)27. | 1 day |