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Cola

Standard Endoscopic Mucosal Resection, if necessary, multi-piece to resect large nonpedunculated homogeneous colorectal lesions (\>20 mm)

Cold Snare Endoscopic Mucosal Resection, if necessary, multi-piece to resect large nonpedunculated homogeneous colorectal lesions (\>20 mm)

Use of injected colloidal or saline solution to raise a lesion prior to polypectomy snare closed over a polyp with electrocautery

Standard Endoscopic Mucosal Resection

Use of injected colloidal or saline solution to raise a lesion prior to polypectomy snare closed over a polyp without electrocautery

Cold Snare Endoscopic Mucosal Resection

Oscar Nogales

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

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.

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.

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

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

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

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.

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

Number of fragments needed to resect with polypectomy snare to complete the resection of the colorectal lesion.

Time needed to perform endoscopic mucosal resection measured from first snare positioning until complete resection is achieved based on endoscopic assessment.

Number of lesions that have undergone resection in a single fragment with each of these evaluated techniques.

Number of lesions with complete macroscopic resection with a negative microscopic margin in the mucosectomy specimen

Number of lesions to be finally resected with the other arm of study technique not initially assigned

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

Number of clip used for hemostatic purposes or for the prophylactic closure of the injury

Subjective impression of the artifact in the histological interpretation of the resected sample (null, moderate, severe)

Measure the depth of the resected submucosa layer (in microns) with each of the resection techniques used

Assess the percentage of presence of mucosal muscle in biopsies performed on the protrusions present in the resection defect of cold-EMR

Number of lesions that have to be finally resected by surgery due to technical impossibility for their endoscopic resection.

evaluate the cost-effectiveness of each of the endoscopic mucosal resection techniques

A subanalysis of the study results by center will be carried out to rule out significant differences between them

Spanish Society of Digestive Endoscopy

Principal Investigator

Conventional Endoscopic Mucosal Resection (EMR), if necessary, to 15-40mm laterally spreading adenomas.

Cold Snare Endoscopic Mucosal Resection (EMR), if necessary, to 15-40mm laterally spreading adenomas.

Use of injected chromogelofusine solution to raise a lesion prior to polypectomy snare closed over a polyp with electrocautery

Conventional Endoscopic Mucosal Resection

Use of injected chromogelofusine solution to raise a lesion prior to polypectomy snare closed over a polyp without electrocautery

Kathleen Goodrick

Kathleen Goodrick, BN

Michael Bourke, MBBS

Comparing the complete resection rate and subsequent adenoma recurrence rate at surveillance colonoscopy of 15-40mm laterally spreading adenomas for conventional EMR vs. cold snare EMR.

Colorectal cancer (CRC) is the third most common malignancy worldwide and the fourth leading cause of cancer related death, with rates being highest in Western countries. Colonoscopy is considered the golden standard in colorectal cancer screening and endoscopic resection of precursor lesions (polyps) has been shown to reduce colorectal cancer death. Polyps extending over 10mm, also referred to as lateral spreading lesions (LSL) if non-pedunculated, more often demonstrate advanced histological features and are considered to be at greater risk for malignant transition as compared to their smaller counterparts. Incomplete endoscopic resection of advanced adenomas may lead to adenoma recurrence and contribute to the development of so called 'interval cancers', which occur during the 6 - 36 month period following complete colonoscopy. Interval cancers account for up to 6% of newly diagnosed CRC cases, highlighting the importance of complete resection.

Endoscopic mucosal resection (EMR) is a well-established inject and resect method for the removal of LSLs using chromo-gelofusin based submucosal lift and subsequent cauterisation assisted snare excision. Lesions up to 25mm in size may be removed enbloc, whereas larger lesions are generally removed in a piecemeal fashion. Contrary to enbloc resection, piecemeal EMR is historically associated with relatively high recurrence rates of 15-20%. A recent four centre trial led by Westmead Hospital published in gastroenterology (impact factor 20.8) has shown that application of snare-tip soft coag (STSC) to the EMR defect margins considerably improves recurrence rates to around 7% in adenomatous LSL. Common complications of EMR such as intra-procedural bleeding (IPB) or clinically significant post-procedural bleeding (CSPB), deep mural injury (DMI) and post-polypectomy coagulation syndrome (PPCS) are largely related to the use of cauterisation for tissue transection. Although complication rates have improved and effects can often be managed endoscopically, further optimization of the EMR safety profile is needed in the background of an aging target population with multiple co-morbidities and widespread use of anticoagulants.

Cold snare polypectomy (CSP) has become the standard of care for removal of subcentimeter polyps. CSP relies on the use of dedicated stiff thin wire snares that are able to swiftly cut through mucosal tissue without the need for cauterisation, leaving intact the muscularis mucosa and the deeper submucosal layers, virtually excluding the risk of perforation. The absence of delayed cauterisation effect significantly reduces the risk of post-polypectomy bleeding, even in patients on anticoagulant therapy. Complete resection rates of polyps ranging from 6 to 10mm in size were found to be non-inferior in CSP as compared to cauterisation based resection. Moreover, resecting a sufficient margin of normal mucosa surrounding the polyp (i.e. \>1mm) yields an excellent 98% complete resection rate in polyps \<10mm in size without increasing the risk of delayed bleeding. Meta-analysis demonstrated a significantly shorter procedure time when applying the cold snare resection technique in small polyps. Snare size limitations of dedicated cold snares however do not allow for en-bloc resection of polyps \>10mm.

Recently, cold snare piecemeal EMR was shown to be safe and effective for the removal of large sessile serrated polyps (SSP). Combined evidence from a limited number of small single centre mostly retrospective studies investigating cold snare piecemeal polypectomy in adenomas over 10mm demonstrated recurrence rates of around 11% whilst maintaining an excellent safety profile with minimal complication rates. However, recurrence rates rise to 22% in the subgroup of polyps over 20mm. Thus far cold snare piecemeal polypectomy of lateral-spreading adenomas has not yet been compared to conventional EMR in prospective randomized fashion.

Conventional Endoscopic Mucosal Resection Versus Cold Snare Endoscopic Mucosal Resection of Colonic Lateral Spreading Lesions - A Randomised Controlled Trial

Conventional Versus Cold Snare Endoscopic Mucosal Resection of Colonic Lateral Spreading Lesions - A Randomised Controlled Trial

Complete resection rate (CRR) as determined by endoscopic assessment (no visible residual adenoma) and histological assessment (biopsies of resection margin)

Adenoma recurrence rate (ARR) at SC1 as determined by endoscopic assessment (no visible recurrent adenoma) and histological assessment (scar biopsies)

Time needed to perform polyp resection measured from first snare positioning until complete resection is achieved based on endoscopic assessment, and total procedure time from insertion of the scope until all specimens have been collected and the scope withdrawal is completed.

Intra-procedural and post-procedural complications rates (IPB / CSPB / DMI / PPCS) as previously described

Western Sydney Local Health District

Professor

Standard cold EMR technique with adjuvant snare tip soft coagulation to defect margins

Use of injected chromogelofusine solution to raise a lesion prior to polypectomy. Lesion then removed with a stiff thin-wired snare. Following this defect margins are treated with electrocautery to create a rim of ablated tissue.

Cold Snare Endoscopic mucosal resection with adjuvant snare tip soft coagulation

Use of injected chromogelofusine solution to raise a lesion prior to polypectomy. Lesion then removed with a stiff thin-wired snare.

Randomised controlled trial comparing cold snare endoscopic mucosal resection (EMR) with cold snare EMR and adjuvant margin STSC in the complete resection of 15-40mm lateral-spreading adenomas

Rationale:

Conventional EMR is well-established for the resection of lateral-spreading adenomas and has been shown to be highly efficacious with adjuvant STSC. Cauterisation-related complications occur relatively frequently and while endoscopically treatable, still carry morbidity not seen in current cold snare polypectomy data.

Cold snare polypectomy has an excellent safety profile for smaller polyps, without cauterisation-related adverse events. Limited data on cold EMR for large adenomatous laterally-spreading lesions shows minimal complications. Efficacy, however, is yet to be evaluated in prospective randomised trials. Observational data demonstrates recurrence rates exceeding conventional EMR. Since STSC causes significant reduction in recurrence in conventional EMR, the safety and efficacy of this adjuvant technique, when compared to isolated cold snare EMR, has theoretical advantages in both safety and efficacy.

The safety and efficacy of these two techniques will therefore be compared in a randomised controlled trial.

Hypothesis:

Cold snare EMR of 15-40mm lateral-spreading adenomas with adjuvant STSC is expected to be superior regarding complete resection and adenoma recurrence rates as compared to cold snare EMR.

Cold Snare Endoscopic Mucosal Resection (EMR) vs Cold EMR With Margin Snare Tip Soft Coagulation (STSC)

Cold Snare Endoscopic Mucosal Resection vs Cold Snare Endoscopic Mucosal Resection With Adjuvant Thermal Therapy to Resection Margins - A Randomised Controlled Trial

Determined by endoscopic assessment (no visible residual adenoma) and histological assessment (biopsies of resection margin)

ARR at first surveillance colonoscopy (SC1) as determined by endoscopic assessment (no visible recurrent adenoma) and histological assessment (scar biopsies)

Intraprocedural bleeding, clinically significant post-polypectomy bleeding, deep mural injury, post polypectomy coagulation syndrome

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cold EMR Vs Standard EMR for the Treatment of Large Nonpedunculated Homogeneous Colorectal Lesions	NCT04418843	Adenoma Colon Serrated Polyp Serrated Adenom... Colorectal Neop...	Standard Endosc... Cold Snare Endo...	18 Years -	Hospital General Universitario Gregorio Marañon
Cold EMR Vs Standard EMR for the Treatment of Large Nonpedunculated Homogeneous Colorectal Lesions	NCT04418843	Adenoma Colon Serrated Polyp Serrated Adenom... Colorectal Neop...	Standard Endosc... Cold Snare Endo...	18 Years -	Hospital General Universitario Gregorio Marañon
Conventional Endoscopic Mucosal Resection Versus Cold Snare Endoscopic Mucosal Resection of Colonic Lateral Spreading Lesions - A Randomised Controlled Trial	NCT04138030	Adenoma Colon Colon Adenoma Colon Cancer	Conventional En... Cold Snare Endo...	18 Years - 99 Years	Western Sydney Local Health District
Conventional Endoscopic Mucosal Resection Versus Cold Snare Endoscopic Mucosal Resection of Colonic Lateral Spreading Lesions - A Randomised Controlled Trial	NCT04138030	Adenoma Colon Colon Adenoma Colon Cancer	Conventional En... Cold Snare Endo...	18 Years - 99 Years	Western Sydney Local Health District
Cold EMR Vs Standard EMR for the Treatment of Large Nonpedunculated Homogeneous Colorectal Lesions	NCT04418843	Adenoma Colon Serrated Polyp Serrated Adenom... Colorectal Neop...	Standard Endosc... Cold Snare Endo...	18 Years -	Hospital General Universitario Gregorio Marañon
Cold Snare Endoscopic Mucosal Resection (EMR) vs Cold EMR With Margin Snare Tip Soft Coagulation (STSC)	NCT05041478	Colorectal Poly... Colon Adenoma Colon Cancer	Cold Snare Endo... Cold Snare Endo...	18 Years -	Western Sydney Local Health District

Spots Global Cancer Trial Database for cold snare endoscopic mucosal resection