Trial of Underwater Versus Gas-Insufflation Colorectal Endoscopic Submucosal DisseEtion (TIDE)

Underwater Versus Conventional Endoscopic Submucosal Dissection For Colorectal Neoplasia: A Multicenter, Randomised Controlled Trial

Colorectal endoscopic submucosal dissection (ESD) enables en bloc resection of large superficial colorectal neoplasia but remains technically demanding and may be limited by suboptimal visualization, intraprocedural bleeding, smoke accumulation, and prolonged procedural time. Underwater ESD (UESD), performed under saline immersion rather than gas insufflation, has been proposed as a strategy to improve the operative field and facilitate submucosal dissection.

This prospective, multicenter, open-label, randomized controlled trial was designed to compare UESD with conventional gas-assisted ESD (GESD) for colorectal neoplasia referred for ESD across Italian tertiary centers. The primary objective was to assess non-inferiority of UESD versus GESD in terms of en bloc resection. Secondary objectives included comparison of histological resection quality, procedural efficiency, intraprocedural events, procedural field visualization, and post-procedural adverse events.

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasia; Colorectal Superficial Neoplasia; Colorectal Precancerous Lesions
• Intervention / Treatment: Procedure: Underwater ESD (UESD); Procedure: Conventional Gas-Assisted ESD (GESD)

Detailed Description

Colorectal ESD is an established organ-preserving technique for the en bloc resection of superficial colorectal neoplasia, particularly when conventional endoscopic mucosal resection is unlikely to achieve complete single-piece excision. However, colorectal ESD is technically demanding because of the thin colonic wall, unstable scope position, narrow submucosal space, intraprocedural bleeding, smoke generation, and difficulty in maintaining a stable dissection plane.

Underwater ESD has emerged as a modified operative environment in which luminal insufflation is discontinued and the target segment is immersed in saline. Saline immersion may improve visualization of the submucosal layer and of submucosal vessels, limit smoke persistence in the operative field, and facilitate more stable dissection. Although initial retrospective and comparative experiences have suggested procedural advantages of underwater ESD, high-quality randomized comparative data remain limited, particularly in Western multicenter practice.

This study was therefore designed as a prospective multicenter randomized trial across Italian tertiary referral centers to compare underwater ESD with conventional gas-assisted ESD for colorectal neoplasia referred for ESD. Patients were allocated 1:1 to either UESD or GESD. The primary endpoint was en bloc resection. Secondary endpoints included R0 resection, procedural time, dissection speed, intraprocedural bleeding, need for hemostatic forceps, smoke interference, vessel visualization, cutting-plane visualization, post-procedural pain, post-ESD coagulation syndrome, perforation, and delayed bleeding. The technical conduct of ESD apart from the assigned luminal environment was left to expert operator discretion in order to preserve real-world tertiary-center practice.

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • RM
    • Rome, RM, Italy, 00100
      • Campus Bio Medico Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Adults aged 19 years or older

Colorectal neoplastic lesion referred for endoscopic submucosal dissection

Lesion considered amenable to en bloc endoscopic resection by ESD according to expert pre-procedural endoscopic assessment

Written informed consent provided

Exclusion Criteria:

Known or suspected deep invasive neoplasia

Inflammatory bowel disease

Uninterrupted antithrombotic therapy

Known coagulopathy

Any clinical or lesion-related condition considered unsuitable for colorectal ESD by the treating endoscopist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Underwater Endoscopic Submucosal Dissection (UESD); Underwater endoscopic submucosal dissection was performed after placement of the lesion on the anti-gravity side whenever feasible, discontinuation of luminal insufflation, and filling of the target colonic segment with saline solution to obtain stable immersion of the operative field. After immersion, mucosal incision and submucosal dissection were completed according to standard ESD principles, using either a conventional stepwise or tunnel-based strategy according to lesion characteristics and operator preference. Only saline solution was standardized across centers; device selection, generator settings, and ancillary maneuvers were otherwise left to operator discretion. Hemostasis, when required, was achieved using hemostatic forceps.	Procedure: Underwater ESD (UESD); Underwater ESD (UESD) performed under saline immersion with luminal insufflation turned off.
Active Comparator: Conventional Gas-Assisted Endoscopic Submucosal Dissection (GESD); Conventional colorectal ESD was performed under gas insufflation according to standard practice at each participating center. Mucosal incision and submucosal dissection were carried out according to standard ESD technique. Device selection, generator settings, and technical dissection strategy were left to operator discretion. Hemostasis, when required, was achieved using hemostatic forceps.	Procedure: Conventional Gas-Assisted ESD (GESD); Conventional colorectal ESD was performed under gas insufflation according to standard practice at each participating center. Mucosal incision and submucosal dissection were carried out according to standard ESD technique. Device selection, generator settings, and technical dissection strategy were left to operator discretion. Hemostasis, when required, was achieved using hemostatic forceps.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
En bloc resection rate	Proportion of lesions resected in a single specimen.	During the index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Proportion of lesions resected en bloc with histologically negative lateral and vertical margins.	During index procedure and histopathological assessment within 30 days
Procedural time	Time from submucosal injection to completion of lesion dissection.	During the index procedure
Dissection speed	Rate of dissection calculated by dividing specimen area by dissection time.	During the index procedure
Intraprocedural bleeding rate	Proportion of procedures with any bleeding occurring during ESD.	During the index procedure
Use of hemostatic forceps	Proportion of procedures requiring coagulation forceps for active bleeding or prophylactic vessel coagulation.	During the index procedure
Smoke interference	Proportion of procedures in which electrocautery-generated fumes/particulate matter impaired visualization and required repeated lens irrigation or temporary withdrawal.	During the index procedure
Vessel visualization score	Operator-reported 5-point Likert score assessing clarity of identification of submucosal vessels during dissection. Lower scores indicate better visualization.	Immediately after the index procedure
Cutting-plane visualization score	Operator-reported 5-point Likert score assessing clarity of the dissection interface between submucosa and muscularis propria. Lower scores indicate better visualization.	Immediately after the index procedure
Post-procedural abdominal pain	Post-procedural pain assessed on a 0-3 numerical scale by nursing staff.	15, 30, and 60 minutes after the procedure
Post-ESD coagulation syndrome (PECS)	Proportion of patients with abdominal distension or pain at the resection site associated with fever or inflammatory response in the absence of documented perforation.	Within 7 days
Perforation rate	Proportion of intraprocedural or delayed perforations.	From procedure to 30 days
Delayed bleeding rate	Proportion of patients with clinically overt post-procedural bleeding or hemoglobin decrease >2 g/dL without another source.	From procedure to 30 days

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Collaborators: Campus Bio-Medico University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): March 1, 2026

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: colorectal neoplasia; endoscopic submucosal dissection; en bloc resection; colorectal ESD; underwater ESD
• Other Study ID Numbers: TIDE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymsed data upon written and motivated requests
• IPD Sharing Time Frame: after the publication, for 5 years at least
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No