Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars

Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars: a Multicentre Randomized Single-blinded Crossover Trial

Nowadays endoscopic mucosal resection (EMR) is the gold standard for the removal of large laterally spreading and sessile colorectal lesions ≥ 20 mm. However, recurrence rate after successful EMR (defined by the absence of neoplastic tissue at the completion of the procedure after careful inspection of the post-EMR mucosal defect and margin) is about 15-20%. Consequently, current guidelines recommend a surveillance colonoscopy between 4 and 6 months after resection for detection of residual or recurrent polyp.

There are few studies that have examined the accuracy of advanced endoscopic imaging for the prediction of histological recurrence but none of these imaging modalities have been validated for surveillance after EMR. Therefore, current guidelines strongly recommend systematic biopsy of EMR scar.

The main aim of this study is to assess the incremental benefit of narrow band imaging (NBI) and white light endoscopy (WLE) randomizing the initial technique for the endoscopic detection of post-EMR recurrence and to asses if this advanced imaging method achieve sufficient diagnostic accuracy to exclude recurrence without the need for biopsy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Recurrence, Local Neoplasm
• Intervention / Treatment: Diagnostic test: WLE followed by NBI or NBI followed by WLE (crossover design)

Detailed Description

a. Study type: multicenter randomized crossover trial: i. prospective inclusion of consecutive patients undergoing first follow-up surveillance colonoscopy after successful EMR of colorectal lesion; ii. crossover randomization by computer generated tables; iii. allocation concealment by sealed, opaque envelopes; iv. pathologist-blinded - pathologists are blinded to the study protocol and samples are received as 'EMR scar for assessment' .

b. Selection patient method: inclusion by invitation of patients undergoing the first follow-up surveillance colonoscopy after successful EMR of colorectal lesion.

c. Sample size: 210 (two groups of 105 patients). To improve accuracy from 85% (value obtained by a study that did not show significant differences in the accuracy of NBI followed by WLE vs. WLE followed by NBI) to 95% and assuming a normal distribution and a power of 80% (α=0.05), the calculated sample size of each of the 2 groups was 96; allowing for a 10% dropout rate, the sample size is 105 per group (210 patients overall).

d. Procedures and data collection methods: i. Each procedure is performed by the same endoscopist. ii. All patients receive split dose bowel preparation. iii. All colonoscopies are performed using high definition colonoscopes with NBI ( EVIS EXERA III CV 185 and CV 190; Olympus Inc., Tokyo, Japan). iv. Colon inspection is done with WLE during withdrawal. v. At the proximity of the scar WLE and NBI were used randomly one after the other (WLE>NBI or NBI>WLE). If NBI is the first technique used, it is switched prior to scar detection, avoiding, as far as possible, a glance with WLE. The edges of the scar are interrogated followed by the centre of the scar and finding are recorded. vi. After both evaluations, if there is no suspicion of recurrence, the site is sampled by at least 2 biopsies of the scar edge. If there is any suspicion of recurrence, tissue sample is obtained and then treated by endoscopic resection using standard methods. At least 2 biopsies specimens from normal appearing scar are also obtained.

e. Analysed variables: i. patient characteristics; ii. data from baseline colonoscopy; iii. data from first surveillance colonoscopy (see outcome measures).

f. Statistical analysis: i. Performed using statistical software IBM SPSS Statistics, Version 25.0. Armonk, NY: IBM Corp. ii. Continuous variables are reported as mean and standard deviation or median and interquartile range, if they have normal or not normal distribution, respectively; categorical variables as absolute and relative frequency. iii. Continuous variables are compared between two groups using Student's T test if they have a normal distribution and homogeneity of variance or Mann-Whitney U if these conditions are not met. Categorical variables are compared using Pearson's X2 test or Fisher test. iv. Sensitivity, specificity, negative and positive predictive values and accuracy are calculated using 2x2 contingency tables. v. All hypotheses are two-tailed and a P-value<0.05 is considered statistically significant.

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Coimbra, Portugal, 3001 - 651
    • Portuguese Oncology Institute - Coimbra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients undergoing the first follow-up surveillance colonoscopy after successful EMR of colorectal lesion.

Exclusion Criteria:

• informed consent not provided,
• inflammatory bowel disease, inadequate bowel preparation (Boston Bowel Preparation Scale total score < 6 or < 2 in a segment),
• EMR scar not identified during colonoscopy,
• tissue acquisition unfeasibly.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A: WLE followed by NBI; EMR scar is interrogated using WLE followed by NBI	Diagnostic test: WLE followed by NBI or NBI followed by WLE (crossover design); EMR scar is inspected using WLE followed by NBI or vice versa; Other Names: WLE followed by NBI or NBI followed by WLE
ACTIVE_COMPARATOR: Group B: NBI followed by WLE; EMR scar is interrogated using NBI followed by WLE	Diagnostic test: WLE followed by NBI or NBI followed by WLE (crossover design); EMR scar is inspected using WLE followed by NBI or vice versa; Other Names: WLE followed by NBI or NBI followed by WLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of WLE and NBI for each group	Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of NBI and WLE for each group calculated using 2x2 contingency tables	1 day (at the time of data analysis)
Recurrent adenoma - WLE	WLE recurrent adenoma identification for each group	1 day (during colonoscopy)
Recurrent adenoma - NBI	NBI recurrent adenoma identification for each group	1 day (during colonoscopy)
Recurrent adenoma - histology	Adenoma recurrence confirmed by histology	1 day (within 30 days from colonoscopy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lesion characterization at the baseline colonoscopy	Lesion size and location, Paris classification, NICE classification, number of pieces, use of adjunctive ablative techniques and those identification and histology. Data collected by endoscopic reports consultation	1 day (at the time of patient inclusion)
Scar characterization at the first surveillance colonoscopy	Scar size, presence or absence of recurrence, in case of recurrence: number of sites, location (edge of the scar, within the scar or both), morphology of recurrence, NICE classification (for NBI evaluation)	1 day (immediately after first surveillance colonoscopy)

Collaborators and Investigators

• Sponsor: Portuguese Oncology Institute, Coimbra
• Investigators: Study Director: Miguel Areia, PhD, Gastroenterology department

Publications and helpful links

General Publications

• Hassan C, Quintero E, Dumonceau JM, Regula J, Brandao C, Chaussade S, Dekker E, Dinis-Ribeiro M, Ferlitsch M, Gimeno-Garcia A, Hazewinkel Y, Jover R, Kalager M, Loberg M, Pox C, Rembacken B, Lieberman D; European Society of Gastrointestinal Endoscopy. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2013 Oct;45(10):842-51. doi: 10.1055/s-0033-1344548. Epub 2013 Sep 12.
• The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003 Dec;58(6 Suppl):S3-43. doi: 10.1016/s0016-5107(03)02159-x. No abstract available.
• Rembacken B, Hassan C, Riemann JF, Chilton A, Rutter M, Dumonceau JM, Omar M, Ponchon T. Quality in screening colonoscopy: position statement of the European Society of Gastrointestinal Endoscopy (ESGE). Endoscopy. 2012 Oct;44(10):957-68. doi: 10.1055/s-0032-1325686. Epub 2012 Sep 17. No abstract available.
• Tate DJ, Desomer L, Klein A, Brown G, Hourigan LF, Lee EY, Moss A, Ormonde D, Raftopoulos S, Singh R, Williams SJ, Zanati S, Byth K, Bourke MJ. Adenoma recurrence after piecemeal colonic EMR is predictable: the Sydney EMR recurrence tool. Gastrointest Endosc. 2017 Mar;85(3):647-656.e6. doi: 10.1016/j.gie.2016.11.027. Epub 2016 Nov 28.
• Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, Jover R, Langner C, Bronzwaer M, Nalankilli K, Fockens P, Hazzan R, Gralnek IM, Gschwantler M, Waldmann E, Jeschek P, Penz D, Heresbach D, Moons L, Lemmers A, Paraskeva K, Pohl J, Ponchon T, Regula J, Repici A, Rutter MD, Burgess NG, Bourke MJ. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2017 Mar;49(3):270-297. doi: 10.1055/s-0043-102569. Epub 2017 Feb 17.
• Desomer L, Tutticci N, Tate DJ, Williams SJ, McLeod D, Bourke MJ. A standardized imaging protocol is accurate in detecting recurrence after EMR. Gastrointest Endosc. 2017 Mar;85(3):518-526. doi: 10.1016/j.gie.2016.06.031. Epub 2016 Jun 22.
• Kandel P, Brand EC, Pelt J, Ball CT, Chen WC, Bouras EP, Gomez V, Raimondo M, Woodward TA, Wallace MB; EMR SCAR Group. Endoscopic scar assessment after colorectal endoscopic mucosal resection scars: when is biopsy necessary (EMR Scar Assessment Project for Endoscope (ESCAPE) trial). Gut. 2019 Sep;68(9):1633-1641. doi: 10.1136/gutjnl-2018-316574. Epub 2019 Jan 11.
• Riu Pons F, Andreu M, Gimeno Beltran J, Alvarez-Gonzalez MA, Seoane Urgorri A, Dedeu JM, Barranco Priego L, Bessa X. Narrow band imaging and white light endoscopy in the characterization of a polypectomy scar: A single-blind observational study. World J Gastroenterol. 2018 Dec 7;24(45):5179-5188. doi: 10.3748/wjg.v24.i45.5179.
• Hayashi N, Tanaka S, Hewett DG, Kaltenbach TR, Sano Y, Ponchon T, Saunders BP, Rex DK, Soetikno RM. Endoscopic prediction of deep submucosal invasive carcinoma: validation of the narrow-band imaging international colorectal endoscopic (NICE) classification. Gastrointest Endosc. 2013 Oct;78(4):625-32. doi: 10.1016/j.gie.2013.04.185. Epub 2013 Jul 30.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2020
• Primary Completion (ACTUAL): May 31, 2022
• Study Completion (ACTUAL): May 31, 2022

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: January 20, 2020
• First Posted (ACTUAL): January 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: recurrence; colorectal lesions; endoscopic mucosal resection; advanced endoscopic imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplastic Processes; Recurrence; Neoplasm Recurrence, Local
• Other Study ID Numbers: PortugueseOIC 004

Drug and device information, study documents

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