Society: ASGE

Background: The most common complication after endoscopic mucosal resection (EMR) is delayed bleeding (DB), especially in the proximal colon. Randomized controlled trials in high volume centers suggest that prophylactic clipping (PC) of the resection defect reduces DB in patients with a high DB risk. Guidelines already recommend PC for proximal polyps, despite being technical difficult and expensive. We aimed to evaluate the value of PC in patients receiving EMR for proximal flat polyps in reducing DB in daily clinical practice.
Methods: We performed a randomized controlled trial in 19 Dutch hospitals with patients referred for EMR of lateral spreading and sessile polyps ≥ 20mm in the proximal colon. Patients were randomly assigned (1:1) to groups treated with PC (intervention group) or no PC (control group). PC was standardized in tutorial meetings focusing on approximating the resection margins with aligning clips 5-10mm apart. The primary endpoint was clinically significant DB defined as hematochezia necessitating emergency department presentation, hospitalization, or re-intervention within 30 days post-EMR, which was analyzed according to the intention-to-treat principle. The trial is registered at ClinicalTrials.gov, NCT03309683.
Results: Between May 15, 2018 and December 14, 2021, 356 patients with a median polyp size of 30mm (IQR 25,40) were included of whom 179 were randomly assigned to the control group and 177 to the intervention group. DB occurred in 11 (6.1%) patients of the control group and in 16 (9.0%) patients of the intervention group (p=0.30). Endoscopists reported complete defect closure in 70.6% of cases. There were no differences between the control and intervention group in serious adverse events including perforation (two versus one, p=0.57), post polypectomy syndrome (zero versus three, p=0.08) and intensive care unit admission (one versus one). No deaths were reported.
Conclusion: PC did not reduce DB in patients undergoing EMR for large lateral spreading and sessile polyps in the proximal colon. Therefore, this study demonstrates that the burden of laborious and expensive PC is not justified in daily clinical practice.
Funding: The CLIPPER trial is investigator initiated and is financially supported by the Dutch Digestive Foundation (MLDS). Olympus (Japan) contributed Quick Clip Pro endoclips for this trial.

Introduction
The US Multi-Society Task Force on Colorectal Cancer recommends referral to an endoscopist experienced in advanced polypectomy for management of large colorectal polyps. It is known that prior manipulation of polyps such as biopsy, attempted resection, or tattoo placement increases the risk of fibrosis and adverse outcomes including incomplete endoscopic mucosal resection (EMR). Delays in referral and scheduling for definitive endoscopic resection are often encountered in practice. It is unclear if timing to between the index procedure and definitive resection affects outcomes of previously manipulated polyps.

Methods
All patients who underwent EMR between 2016 and 2021 were identified from a prospectively-maintained procedure database at a tertiary referral center. Index colonoscopy reports were reviewed and only previously manipulated polyps >10 mm referred for EMR were included. Patient, polyp, procedure, and outcome-related variables were retrospectively collected. Timing between index colonoscopy and definitive resection was calculated. Polyps referred and resected within 6 weeks were compared to those referred and resected after.

Results
Of 320 procedures screened, 247 lesions were included; 131 were females (54%). At the time of referral for EMR, 201 (69%) had been biopsied, 29 (12%) had previous attempted resection, and 22 (9%) had a tattoo extending to the base of the lesion. At EMR, fibrosis was noted in 62 (25.3%). Mean number of weeks between index colonoscopy and definitive resection was 9.1 ± 10.5. There were no significant differences in age, gender, polyp size, polyp location between polyps resected within 6 weeks and those resected after [Table 1]. Previously manipulated polyps referred and resected within 6 weeks of index colonoscopy had a significantly lower incidence of fibrosis (19.2%) versus those resected after (31.2%), p=0.030. A multivariate analysis controlling for polyp size showed that resection within 6 weeks continued to show 49% lower odds of fibrosis (p=0.028). Polyps with fibrosis had significantly lower en-bloc resection rates (9.7% vs. 22.4%, p=0.028), longer procedure time (72 vs. 52 minutes, p<0.0001), and lower Sydney resection quotient (3.9 vs. 8.2, p=0.001). There was no significant difference in adverse events or recurrence [Table 2].

Conclusion
In this study of previously manipulated polyps >10mm undergoing EMR, we found that delay between referral and definitive resection beyond 6 weeks was associated with a higher risk of fibrosis. Presence of fibrosis was associated with inferior outcomes including longer procedure time, lower en-bloc resection rate, and lower Sydney resection quotient. To our knowledge, this is the first series examining timing of definitive resection and EMR outcomes. If externally validated, our findings support expedited definitive resection for previously manipulated lesions.

<b>Table 1</b>: Baseline patient & polyp characteristics by timing from index colonoscopy to definitive resection.

Table 1: Baseline patient & polyp characteristics by timing from index colonoscopy to definitive resection.

<b>Table 2:</b> Primary outcomes of previously manipulated polyps by presence of fibrosis at time of resection.

Table 2: Primary outcomes of previously manipulated polyps by presence of fibrosis at time of resection.

Background: Endoscopic resection is highly effective for large colorectal neoplasia removal. However, recurrent or residual lesions are common and pose a clinical challenge. Salvage endoscopic submucosal dissection (ESD) has been recommended as a treatment option for previously attempted colorectal lesions (PACL). ESD has the advantage of achieving en bloc resection, yet the presence of extensive submucosal fibrosis in PACL impacts procedural difficulty and resection outcomes. A few small single center studies, mostly from Asia, have evaluated the role of salvage ESD for PACL, but data from Western centers is limited.

Aims: To evaluate the efficacy and outcomes of salvage ESD for the treatment of PACL in the Western population.

Methods: Consecutive patients who underwent ESD for the management of PACL between 05/2014-10/2022 at 19 tertiary care centers (15 North America, 2 South America, 2 Europe) were included. Primary outcomes were rate of en bloc and R0 resection. Secondary outcomes were rates of adverse events (AEs) [severity graded per Classification for Adverse events Gastrointestinal Endoscopy (AGREE)], procedure-related mortality, need for surgical management, and local recurrence.

Results: A total of 360 PACL treated by ESD were included (Table 1). En bloc rate was 89.7%, R0 81.1%, and curative resection of 79.4%. Overall, AEs occurred in 41 (11.4%) patients, most common being intraprocedural perforation (n=17; 4.7%). One patient required surgical management and 16 were managed endoscopically. Severe intraprocedural bleeding occurred in 3 (0.8%), all managed endoscopically. The mean ± SD procedure time was 94.7 ± 58 minutes. In 291 (80.8%) patients, ESD was performed in an outpatient setting; the remaining patients were admitted for observation (median (IQR) length of hospital stay (LOS): 1 (0-2) days). 21 patients (5.8%) had post-ESD AEs at the median of 7 (1-36) days, most commonly being delayed bleeding (1.9%). A total of 4 (1.1%) patients required surgery (1 intraprocedural perforation, and 3 post-ESD AEs [colonic stricture, fistula formation, and abscess]. Of 281 patients with follow-up data, local recurrence occurred in 14 (5%) patients after a median follow-up of 49 (25, 72) weeks. There was no mortality from procedure-related or colorectal cancer (Table 2).

Conclusion: Salvage ESD is highly effective in the treatment of PACL. Our data showed a high rate of en bloc and R0 resection for this challenging lesion, with very low overall rate (1.1%) of surgery. When performed by experts, AEs were uncommon and mostly managed endoscopically. These results support role of ESD for PACL in the Western setting.

<b>Table 1.</b> Baseline characteristics for patients with previously attempted colorectal lesions (PACL) undergoing salvage endoscopic submucosal dissection (ESD), n (%)

Table 1. Baseline characteristics for patients with previously attempted colorectal lesions (PACL) undergoing salvage endoscopic submucosal dissection (ESD), n (%)

<b>Table 2.</b> Procedural outcomes for patients with previously attempted colorectal lesions (PACL) who underwent salvage endoscopic submucosal dissection (ESD), n (%)

Table 2. Procedural outcomes for patients with previously attempted colorectal lesions (PACL) who underwent salvage endoscopic submucosal dissection (ESD), n (%)

Introduction
ESD is the gold standard of treatment for large superficial colorectal lesions in Asia.
In Western countries, it is struggling to establish itself as the reference treatment because of its technical difficulty. France, after publishing worrying results 10 years ago, has set up effective training allowing a wide territorial offer. Despite the results reported by expert centers, there is still a debate about the feasibility of colonic dissection compared to rectal dissection due to the greater technical difficulty and the higher risk of complications in this location. The aim of this study was to analyze 3 years after the creation of the prospective French ESD colorectal cohort (FECCO), the results of colorectal ESD, with focusing on comparison between colonic and rectal ESD.
Patients and Methods
This is a prospective cohort that included all colorectal ESD performed in 12 French centers and one Belgian center between September 2019 and September 2022.
The objectives of this study were to compare the results of colonic and rectal lesions
and rectal lesions treated by ESD in terms of En bloc, R0, curative resection, perforation rate
clinically significant delayed bleeding rates and in terms of secondary surgery.
Results
Between September 2019 and September 2022, 3901 colorectal ESD were performed
in the 13 centers by 35 operators. The average age of the patients was 68 years,
65% of the cases were granular LST. The average size of the lesions were 54 mm. The lesions were located in the colon in 62% of cases.
The mean procedure time was 73 min and the mean procedure speed was was 34 mm2/min. The rates of en bloc, R0 and curative resection were 95%, 88% and 84% respectively
When comparing rectal and colonic lesions:
-Rectal lesions were significantly larger: (60 mm vs 50 mm, p < 0.0001)
-the procedure time was longer in the rectum than in the colon (84 vs 64
min; p < 0.0001) but procedural speed was significantly higher in the rectum
(36 mm2/min vs 32 mm2/min p<0.001).
-The rate of en bloc resection was higher in the rectum: 96% vs 94%, p=0.041
-There was no difference in terms of R0 resection: 88.3% vs 87%, p=0.231;
-curative resection was significantly more frequent in the colon: 85.6% vs 81.3%, p=0.003
-there was more per-procedural perforation in the colon: 10.6% vs 7.1%, p=0.002
-the surgical referral rate for a complication was higher in the colon: 0.7% vs O.1%, p=0.012
-there was more clinically significant delayed bleeding in the rectum: 4.5% vs 6.8%, p=0.003
-the length of hospital stay was significantly longer for colonic lesions: 1.8 vs 1.5 days, p<0.001
Conclusion
The results of colorectal ESD in France are confirmed on a large scale and the differences between rectal and colonic lesions are negligible when the procedure is mastered leading to the use of ESD as a first line treatment for superficial colorectal lesions larger than 2 cm.

Introduction
ESD has shown in a recent French randomized trial (RESECT COLON Study) to decrease recurrence rate of large adenomas (>25 mm) vs piece-meal EMR without increasing significant adverse events. We performed a post hoc analysis of our randomized study to investigate the environmental impact of these two endoscopic procedures.
Material and method
An independent eco-audit studied the two groups of the RESECT COLON study based on 4 parameters : endoscopes and disposable medical products, electricity consumed, anesthetic products and patient transport. Each device was collected prospectively during trial (medico-economic component), and their environmental impact (CO₂ equivalent) was calculated considering the production site, its transport, its components and their weight, and the packaging. The environmental impact of follow-up colonoscopies (2 kg CO₂ eq) in case of non-R0 resection was evaluated in both arms. The distance of patient transports was measured. Data are expressed in kilograms of CO₂ equivalent. We then modeled 2 additional care organizations : ESD in expert hospital and P-EMR in local hospital (distance divided by 2), versus a strategy with ESD in expert hospital and P-EMR in local hospital only for simple lesions (SMSA<4) with P-EMR in expert hospital for SMSA 4 lésions.
Results
Devices in an ESD emit 14.26 eq kg CO₂, versus 11.39 eq kg CO₂ for a P-EMR. The R0 rate was 93.8% in ESD group versus 6.6% in P-EMR group which leads, according to ESGE guidelines to 189 controls/3 years in the ESD, versus 362 in the P-EMR, i.e. 173 controls avoided.
The 173 controls avoided thus represent 27680 car kilometers avoided and 5536 eqkgCO2e.
The calculated global environmental impact in the ESD group is 14614 eqkgCO2 (devices 2902 eqkgCO₂ and transport 11712 eqkgCO₂) against 20205 eqkgCO₂ for the P-EMR RESECT group (devices 2797 kgCO₂ and transport 8704 eqkgCO₂).
If all P-EMR were performed in local hospital, the impact would be 11501 eqkgCO₂ (devices 2797 eqkgCO₂ and transport 8704 eqkgCO₂) considering an equivalent recurrence rate of 5% (and not 20% as published outside expert hospital).
If SMSA 4 lesions (80%) were sent to an expert hospital to receive ESD (ESGE recommendation), and simple P-EMR in local hospital, the impact would be 18464 eq Kg CO₂.
Conclusion
The ESD for all strategy reduces considerably the environmental impact by reducing the associated controls and transports. If P-EMR could be performed in a local center with the same results than in experts centers, results would be more balanced but, ESGE guidelines recommend sending complex lesions to an expert. Finally, if a patient is referred to an expert center, then ESD should be chosen both for its efficiency results and for its reduced environmental impact. Ideally, in the future, ESD should be made available in less experts’ centers to decrease environmental impact.

Introduction:
Muscle retracting sign is defined by attraction and fusion of the muscle layer into the submucosal layer under big nodular lesions. First described by Pr Toyonaga in 2015, it is associated with less en bloc and R0 resection despite being associated with only fibrosis in half of the cases. View the paucicity of the available data and the absence of western data, we decide to perform a prospective clinical study to evaluate the prevalence and clinical significance of the MRS during colorectal ESD of large nodular lesions.
Methods
Prospective study including all patients treated by colorectal ESD from January 2017 and September 2022 in Rennes university hospital and Limoges university hospital. Non nodular lesions (LDT granular homogenous, NG LST, Neuroendocrine tumor, recurrences, submucosal lesions) or lesions with deep cancer prediction on optical diagnosis (JNET III, SANO IIIB, KUDO Vn).
The primary Endpoint was the evaluation of curative resection rate in case of MRS.
Results:
1600 colorectal lesions were resected by ESD during the study period and 701 large nodular lesions were included in the study (25% protruding lesions and 75% LST granular mixed type). 324 (46%) of the lesions were in the rectum and 377 (54%) were in the colon.
The prevalence of the MRS was 12% (82 MRS). The full cohort en bloc, R0, and curative resection rate was respectively 94%, 83% and 78%.
MRS was associated with at least submucosal cancer in 39% of cases.
The curative resection rate (primary endpoint was significantly lower in case of MRS: 42.5% vs 88% p<0.0001
Ro resection rate was significantly lower in case of MRS: 62.5% vs 85.6% p<0.0001
Perforation rate was significantly higher in case of MRS: 23.5% vs 9.3%
Secondary surgery was significantly more frequent in case of MRS:
Comparing rectal and colonic lesions with MRS:
-en bloc resection rate was higher in rectal lesions with MRS than in colonic lesions with MRS: 85.7% vs 64.6%
-R0 resection rate was not significantly different: 72.7 % (rectum) vs 55.3% (colon) p=0.113
-curative resection rate was not significantly different: 48.5% (rectum) vs 38.3% (colon) p=0.364
-secondary surgery rate was not different: 30% (rectum) vs 46% (colon) p=0.177
Conclusion
Prevalence of MRS in large nodular lesions is high, up to 12%. Curative resection rate is low (42.5%) and perforation rate is very high despite a study performed in very expert centers.
Considering that at least submucosal invasion was present in 40% of cases and that perforation rate was more than 20%, ESD should be stopped in the colon in case of presence of MRS.
However, considering the functional outcome of rectal surgery, the safety even in case of peroration in this location and the 70% free surgery follow-up in the rectum, ESD should be continue in this location.

Hugo Lepetit

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