Adenoma detection by Endocuff-assisted versus standard colonoscopy in an organized screening program: the “ItaVision” randomized controlled trial

• Abstract
• Introduction
• Methods
• Study population
• Randomization
• Colonoscopy procedures
• Histopathology
• Outcome measures
• Sample size
• Statistical analysis
• Ethics
• Results
• Study population
• Per-patient analysis
• Analysis by endoscopists’ ADR
• Adverse events and removal of device
• Discussion
• References

Abstract

Background The Endocuff Vision device (Arc Medical Design Ltd., Leeds, UK) has been shown to increase mucosal exposure, and consequently adenoma detection rate (ADR), during colonoscopy. This nationwide multicenter study assessed possible benefits and harms of using Endocuff Vision in a fecal immunochemical test (FIT)-based screening program.

Methods Patients undergoing colonoscopy after a FIT-positive test were randomized 1:1 to undergo Endocuff-assisted colonoscopy or standard colonoscopy, stratified by sex, age, and screening history. Primary outcome was ADR. Secondary outcomes were ADR stratified by endoscopists’ ADR, advanced ADR (AADR), adenomas per colonoscopy (APC), withdrawal time, and adverse events.

Results 1866 patients were enrolled across 13 centers. After exclusions, 1813 (mean age 60.1 years; male 53.8 %) were randomized (908 Endocuff Vision, 905 standard colonoscopy). ADR was significantly higher in the Endocuff Vision arm (47.8 % vs. 40.8 %; relative risk [RR] 1.17, 95 % confidence interval [CI] 1.06–1.30), with no differences between arms regarding size or morphology. When stratifying for endoscopists’ ADR, only low detectors (ADR < 33.3 %) showed a statistically significant ADR increase (Endocuff Vision 41.1 % [95 %CI 35.7–46.7] vs. standard colonoscopy 26.0 % [95 %CI 21.3–31.4]). AADR (24.8 % vs. 20.5 %, RR 1.21, 95 %CI 1.02–1.43) and APC (0.94 vs. 0.77; P  = 0.001) were higher in the Endocuff Vision arm. Withdrawal time and adverse events were similar between arms.

Conclusion Endocuff Vision increased ADR in a FIT-based screening program by improving examination of the whole colonic mucosa. Utility was highest among endoscopists with a low ADR.

Introduction

Population-based organized colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) have been implemented in several European countries, as recommended by scientific societies [1] [2] [3] [4] [5].

The efficacy of FIT depends on its selective accuracy for advanced adenomas and existing CRCs with an average positivity of 4 %–7 % at each round [6] [7], depending on the hemoglobin cutoff used. The use of FIT results in a 3– to 5-fold increase in the detection of advanced neoplasia at post-FIT + colonoscopy compared with primary screening colonoscopy [8] [9]. Thus, post-FIT + colonoscopy represents a challenging setting with a high burden of colorectal neoplasia, where both diagnostic and operative procedures must be optimized.

Adenoma detection rate (ADR) is a key performance measure of the quality of colonoscopy, and a low ADR has been inversely associated with an increased risk of post-colonoscopy CRC [10] [11] [12] [13]. When assessing ADR of individual endoscopists within a screening program, a substantial degree of ADR variability is also reported [14] [15] [16] [17] [18].

There are two main reasons for the miss rate of neoplasia at colonoscopy. The first reason is failure to recognize a lesion despite fully exposed on the endoscopy monitor owing to operator (distraction, tiredness, skill) or image (low definition) issues [19], and the second is failure to expose the entire surface of the colorectal mucosa due to its folds and angulations, which has only been partially addressed by the wide angle of view and tip maneuverability of the most recent generation of scopes [19]. As the rapid development of artificial intelligence is likely to address the miss rate attributed to recognition errors [20] [21], further improvements are needed to ensure complete exploration of the whole mucosal surface. Add-on devices aimed at flattening and strengthening colorectal mucosa have been claimed to reduce the miss rate of neoplasia [22]. Endocuff Vision (Arc Medical Design Ltd., Leeds, UK) offers the advantage of being inserted immediately behind the tip of the scope without restricting the view of the camera as, for instance, occurs with caps. By straining the fold or angulation with a circular row of soft arms, the Endocuff Vision is expected to increase the percentage of mucosa that is exposed to the camera during withdrawal, reducing the miss rate and increasing the ADR of the endoscopist.

Endocuff has been shown to achieve a moderate increase in ADR in a recent meta-analysis of more than 9000 patients [23]. Interestingly, its effect was more beneficial for low than for high detectors. However, there is residual uncertainty on the possible benefit of Endocuff Vision in FIT-positive patients as this has only been addressed by two studies, with conflicting results [24].

The aim of this nationwide multicenter study was to assess the efficacy and safety of using Endocuff Vision in a FIT-based population screening program.

Methods

ItaVision is a parallel, randomized, multicenter trial that was performed in 13 endoscopy centers participating in 11 organized population CRC screening programs in 6 Italian regions (Friuli Venezia Giulia: Local Health Unit (LHU) of Trieste; Lazio: LHU Roma 1 and LHU Roma 6; Lombardia: ASST Crema, LHU Val Padana; Piemonte: LHU Città di Torino; Tuscany: LHU 10 Firenze; Veneto: LHU 1 Dolomiti, LHU 5 Polesana, LHU 6 Euganea, LHU 8 Berica, and LHU 9 Scaligera). The study was reported according to the CONSORT guidelines for randomized controlled trials [25]. Details of members of the ItaVision Working Group are available in the online-only Supplementary material.

Study population

The target population included patients undergoing colonoscopy within the Italian CRC screening program involved in the study. The screening programs involve residents aged 50 to 69 /75 years, who are invited by mail every 2 years to perform a single FIT, without any dietary restriction. Nonresponders to the first invitation are mailed a reminder, usually within 6 months. The OC-Hemodia latex agglutination test, developed with the OC-Sensor Micro instrument (Eiken, Tokyo, Japan), is used. Quantitative hemoglobin analysis is performed with automated instruments. The cutoff for test positivity is 20 µg Hb/g feces (100 ng Hb/mL buffer). Individuals are notified of their results by mail and people with a negative FIT result are advised to repeat the screening 2 years later. Individuals with a positive screening test are contacted by telephone and invited to undergo colonoscopy at an endoscopy referral center during dedicated sessions. Endoscopists performing colonoscopies within the Italian screening program have to comply with given requirements, namely a training module before entering the program, auditing of performance, and retraining if necessary.

After colonoscopy, patients are referred for surgery, post-colonoscopy surveillance, or further rounds of FIT, depending on outcome. Patients were excluded from the current study if they had a personal history of CRC, or inflammatory bowel disease, previous colonic resection, antithrombotic therapy precluding polyp resection, or were unable to provide written informed consent.

Randomization

Patients were invited by a study investigator to participate in the study when they attended the endoscopy unit and before the screening colonoscopy. All participating patients signed an informed consent form. FIT-positive patients were randomized within screening centers to undergo colonoscopy either with standard white-light colonoscopy (standard colonoscopy) or with white-light colonoscopy plus Endocuff Vision. Randomization was based on a computer-generated randomized block (n = 8) sequence. The randomization sequence was generated using the “ralloc” module in Stata (version 11.0) with a ratio 1:1 and permuted blocks, stratifying within center by sex, age ( < 60, ≥ 60 years), and screening history (first and subsequent FIT screening). Group assignment occurred automatically after the patient characteristics that were relevant for randomization had been recorded in the EPICLIN database (a web-based application for management of clinical studies: www.epiclin.it, developed by CPO Piemonte). Only after entering the characteristics of each enrolled patient in this study database could the endoscopist see the randomization arm assigned to that patient.

Colonoscopy procedures

Colonoscopies were performed by experienced endoscopists ( > 2000 screening colonoscopies) with high- or standard-definition endoscopy systems as available at the study centers. For the purpose of the study, the use of magnification, chromoendoscopy or light-modification technologies was restricted to polyp characterization at the endoscopist’s discretion. Bowel preparation was evaluated and graded by the endoscopist performing the examination, using the Boston Bowel Preparation Scale [26]. Patients with 0 or 1 in any one of the three segments were excluded from the primary analysis. The endoscopist and facility staff were allowed to adopt their standard procedures for patient management and monitoring, including use of conscious sedation. Cecal intubation was assessed by the endoscopist through the identification of the ileocecal valve and the appendiceal orifice via photo documentation. Intubation time and inspection time during withdrawal were measured using a stopwatch, pausing during therapeutic interventions and washing. Endoscopists were required to spend a minimum of 6 minutes for inspection (i. e. clean withdrawal time). All polyps were classified according to their location, size, and morphology using the Paris classification [27]. Location was considered proximal if proximal to the splenic flexure. All polyps were removed (biopsy for nonresectable lesions), irrespective of size, color, or subjective interpretation, with the exception of diminutive hyperplastic-appearing polyps located in the rectum that were deemed not clinically significant by the endoscopist. Endocuff Vision was not used or could be removed at the endoscopist’s discretion, and reasons for removal or non-use were recorded.

Histopathology

All resected or biopsy specimens were fixed in 10 % buffered formalin solution in separate jars. They were processed and stained for histopathology using standard methods and evaluated by expert pathologists participating in the organized screening program (one at each center); pathologists were blinded to the assigned examination mode. All lesions were classified according to the Vienna classification [28]. An advanced adenoma was defined as an adenoma ≥ 10 mm and/or with a ≥ 20 % villous component, and/or high grade dysplasia.

Outcome measures

The primary outcome was ADR according to study arm. ADR was defined as the proportion of patients with at least one histologically proven adenoma or carcinoma, including in situ/intramucosal carcinoma. Sessile serrated lesions (SSLs) were not included in the ADR calculation.

Secondary outcomes were ADR stratified by patient sex and age, and by operating endoscopists’ ADR. The ADRs obtained by the endoscopists in the standard colonoscopy arm were divided into tertiles; the endoscopists were then divided into low, intermediate, and high detectors. Further secondary outcomes were advanced adenoma detection rate, ADR by site (proximal vs. distal), total number of polyps detected, SSL detection rate, mean number of adenomas per colonoscopy, cecal intubation rate, withdrawal time. The proximal ADR was defined as the prevalence of patients with at least one adenoma detected proximal to the splenic flexure (including cecum, ascending, and transverse colon); a sensitivity analysis was also performed to include lesions detected at the splenic flexure as proximal lesions. The adenomas per colonoscopy was defined as the total number of adenomas divided by the number of colonoscopies performed. Adverse events were classified according to the American Society for Gastrointestinal Endoscopy lexicon [29].

Sample size

The primary aim was to demonstrate the superiority of colonoscopy with Endocuff Vision compared with standard colonoscopy in terms of ADR. An increase in ADR of ≥ 15 % has been reported when using the first-generation Endocuff [30]. The average ADR of Italian screening programs in 2017 was 42 % [31].

The study aimed to recruit 2020 patients (1010 in each arm) in order to achieve 80 % power to reject the null hypothesis, with a significance level of 0.05, that the difference between the expected test proportion (πT) and the standard proportion (πS), πT–πS, is not higher than 15 %, in favor of the alternative hypothesis stating that the difference between proportions is superior, assuming that the expected difference in proportions is 0 and the proportion in the standard group is 42 %.

Statistical analysis

All analyses were performed in an intention-to-treat (ITT) framework. A per-protocol analysis was performed for the primary end point, excluding the colonoscopies with inadequate bowel cleansing and those in which Endocuff Vision was not used or where it was removed during the exam.

Differences between arms in the primary outcome and in the other categorical indicators were tested using chi-squared test and Fisher’s exact test. For the comparison of continuous outcomes, the nonparametric two-tailed Mann–Whitney U test was applied, due to the non-normal distribution of data. Estimates of 95 % confidence intervals (CIs) were computed using normal approximation. In order to account for center effects [32] [33] and stratified balanced randomization [34], we also re-examined, as sensitivity analysis, the difference in the primary outcome using a mixed-effects logistic regression model including random effects for centers and fixed effects for treatment and randomization variables (sex, age, and previous screening history).

Statistical significance was set at 0.05 and the analysis was computed using SAS, version 9.4 (SAS Institute, Cary, North Carolina, USA) and R software (R Foundation for Statistical Computing, Vienna, Austria. http://www.r-project.org).

Ethics

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Regional Ethics Committee of Tuscany (n. 11775_spe/2018) and by the local institutional review boards of all participating centers. Written informed consent was obtained from each patient.

Results

Study population

A total of 1866 patients were assessed for eligibility between February 2018 and January 2020. After the exclusion of 50 patients ([Fig. 1]), the study cohort was represented by 1816 randomized patients (53.8 % males). After randomization, 3 patients were excluded due to incomplete data collection (2 Endocuff Vision, 1 standard colonoscopy). Finally, 908 patients were allocated to the Endocuff Vision arm and 905 to the standard colonoscopy arm. [Table 1] reports the main demographic details of study patients and the principal characteristics of colonoscopies, by study arm.

Per-patient analysis

According to the ITT analysis, the ADR was 47.8 % (95 %CI 44.6–51.0) in the Endocuff Vision arm and 40.8 % (95 %CI 37.6–44.0) in the standard colonoscopy arm ([Table 2]). The increase in ADR was statistically significant (relative risk [RR] 1.17, 95 %CI 1.06–1.30). A similar result was obtained from the mixed-effects logistic regression model (RR 1.17, 95 %CI 1.06–1.27).

In the per-protocol analysis, 419 /857 patients in the Endocuff Vision arm were diagnosed with at least one adenoma or CRC at colonoscopy (ADR 48.9 %, 95 %CI 45.6–52.2) compared with 367 /880 patients in the standard colonoscopy arm (ADR 41.7 %, 95 %CI 38.5–45.0).

Regarding morphology, the rate of patients with nonpolypoid lesions was similar in the two groups (Endocuff Vision 4.4 % vs. standard colonoscopy 5.3 %; RR 0.83, 95 %CI 0.55–1.25). Size data were available for 424/434 adenomas in the Endocuff Vision arm (97.7 %) and for 359/369 adenomas in the standard colonoscopy arm (97.3 %). The proportions of patients with ≤ 5 mm, 6–9 mm, and ≥ 10 mm adenomas, respectively, were similar in both groups. Regarding location, the proportion of patients with distal adenomas was higher in the Endocuff Vision arm than in the standard colonoscopy arm (35.5 % vs. 28.7 %; RR 1.23, 95 %CI 1.08–1.41), but it was similar between arms for proximal adenomas (24.2 % vs. 21.0 %; RR 1.15, 95 %CI 0.97–1.37). The sensitivity analysis classifying the adenomas located in the splenic flexure as proximal confirmed these results (data not shown).

A total of 225 patients were diagnosed with advanced adenoma in the Endocuff Vision group compared with 186 patients in the standard colonoscopy group, corresponding to a detection rate for advanced adenomas of 24.8 % and 20.5 %, respectively (RR 1.21, 95 %CI 1.02–1.43). No statistically significant difference between the two groups was found in the proportion of patients with carcinoma (Endocuff Vision 3.2 % [95 %CI 2.1–4.6] vs. standard colonoscopy 2.4 % [95 %CI 1.5–3.7]), or in those with at least one SSL (1.9 % vs. 1.0 %, respectively), or for SSLs with dysplasia (0.4 % vs. 0.5 %, respectively) ([Table 2]).

When stratifying patients by sex and age, Endocuff Vision showed a statistically significant increase in ADR in male patients (54.7 % vs. 47 %; RR 1.16, 95 %CI 1.03–1.32), and in patients aged between 60 and 75 years (54.1 % vs. 45.8 %; RR 1.18, 95 %CI 1.04–1.34) (Table 1 s). Among female patients and patients aged 50–59 years, the use of Endocuff Vision was associated with an increased ADR, without reaching statistical significance.

A total of 857 and 695 adenomas were resected in the Endocuff Vision arm and in the standard colonoscopy arm, respectively. The number of adenomas per colonoscopy was higher in the Endocuff Vision arm than in the standard colonoscopy arm (0.94 vs. 0.77; P  = 0.001). Per-lesion results for secondary outcomes are reported in Table 2 s.

Analysis by endoscopists’ ADR

According to the individual ADR obtained in colonoscopies performed in the standard colonoscopy arm, endoscopists were stratified into low (ADR < 33.3 %), medium (33.3 %–47.4 %), and high ( > 47.4 %) detectors. The use of Endocuff Vision resulted in a statistically significant increase in the ADR among low detectors (41.1 % [95 %CI 35.7–46.7] vs. 26.0 % [95 %CI 21.3–31.4]), but not among medium and high detectors ([Table 3]). The statistically significant increase was also maintained among low detectors, but not among medium or high detectors, when only advanced adenomas were considered (23.1 % [95 %CI 18.8–28.0] vs. 13.5 % [95 %CI 10.1–17.8]).

When stratifying by adenoma dimension, low detectors saw an increase in their ADR both for adenomas ≤ 5 mm (Endocuff Vision 11.8 % vs. standard colonoscopy 6.1 %; P = 0.04) and ≥ 10 mm (15.6 % vs. 9.0 %; P  = 0.02), while medium and high detectors did not show statistically significant increases in ADR for any adenoma size ([Fig. 2], Table 3 s). In low detectors, a statistically significant benefit was observed for both proximal and distal neoplasia.

Adverse events and removal of device

A total of four adverse events (0.2 %) were recorded in the study cohort – three post-procedural bleedings and one perforation. No difference in adverse events was found between study arms ([Table 4]).

Among the 908 patients randomized to Endocuff-assisted colonoscopy, the device was removed during the procedure in 27 cases (3.0 %) and was not used in 1 case (0.1 %). The most common reason for removal of the device was diverticular disease (n = 11; 39.3 %), followed by sigmoid colon anatomy (n = 8; 28.6 %) and stenosis (n = 6; 21.4 %). Unbearable pain required the removal of the Endocuff Vision in two cases (0.2 %). Removal of Endocuff Vision did not differ among high (11 /303; 3.6 %), intermediate (5 /284, 1.8 %), or low (11 /321; 3.4 %) detectors (P  = 0.30).

Discussion

Our study, which included more than 1800 FIT-positive patients, is the largest available randomized controlled trial to date on Endocuff Vision: the two previous studies addressing the role of Endocuff Vision in FIT-positive patients, included 797 and 534 in a multicenter (ADENOMA) and single-center (E-cap) setting, respectively [35] [36]. Unlike these studies, we excluded any patient under post-polypectomy surveillance, even within the organized program, as these patients are known to be at very low risk of residual advanced neoplasia compared with the first FIT-positive colonoscopy.

The main findings of our study, which was performed within an organized FIT-based screening program, were that the use of Endocuff Vision was associated with a 17 % increase in ADR, a statistically significant increase in adenomas per colonoscopy, and a 21 % increase in the detection of advanced adenomas. The remarkable benefit of Endocuff Vision is clinically relevant, as the overall efficacy of FIT-based programs is related to the removal of neoplasia – especially advanced – in individuals with a positive FIT result. By increasing the detection of colorectal (advanced) neoplasia, the benefit of Endocuff Vision is not limited to the performance of colonoscopy but extends to the whole organized program.

According to our study, the main driver of Endocuff Vision efficacy was the 15 % absolute ADR increase in low detectors, while no additional efficacy was observed in high detectors. This confirms, in a FIT-positive setting, the benefit of Endocuff Vision in operators with low ADR, as recently reported in a meta-analysis of studies performed mainly in a primary endoscopic screening setting [23]. Overall, our data support the notion that the main reason behind low detection is incomplete exposure of colorectal mucosa rather than recognition failure.

The benefit of Endocuff Vision for low detectors in our study was not limited to diminutive lesions, as already widely accepted, but extended to large lesions (≥ 10 mm), where use of the device improved the ADR from 9 % to 16 %, underlining the possible contribution of Endocuff Vision in preventing post-colonoscopy CRC in FIT-positive individuals undergoing colonoscopy by endoscopists with low ADRs. When considering detection of advanced adenomas only, a statistically significant increase was also observed among low detectors.

Of interest, the statistical association between Endocuff Vision benefit and distal location is mainly explained by the enrichment effect of FIT for distal advanced neoplasia, as a similar benefit for both proximal and distal neoplasia was shown with Endocuff Vision in the group of low detectors (Table3 s). Another possible explanation is the reduced width of the distal colon, giving the Endocuff Vision device an additional advantage in this region.

The fact that our study did not confirm the lack of benefit shown in the E-cap study in an organized program is not fully unexpected [36]. The E-cap study was performed in a single tertiary colonoscopy setting, where all four endoscopists had a very high baseline ADR (i. e. mean 63 %; all > 55 %), with findings corresponding to the lack of any benefit found in high detectors in our study. Conversely, our findings are in line with the benefit of Endocuff Vision in FIT-positive individuals found in the ADENOMA trial, where the mean ADR was 10 points lower than in the E-cap study (50.9 %), although no analysis on individual endoscopists was provided [35] [36].

Our study also confirms the technical feasibility of Endocuff Vision in an organized setting. Despite the fact that more than 70 % of colonoscopies were performed under conscious sedation, Endocuff Vision was removed in only about 3 % of cases, representing minimal resource waste, which is relevant in a public service setting. Endocuff Vision did not appear to interfere with the inspection time, which was more than 6 minutes in both arms. The inclusion of Endocuff Vision in the screening setting seems feasible; however, before extensive implementation can occur, a cost-effectiveness analysis might be informative, especially one that considers the different impact of the device between high and low detectors.

The main limitations of our study relate to the fact that it was single blinded and that ADR rather than post-colonoscopy CRC was the study end point. The ADR in our standard colonoscopy arm was precisely equivalent to the average ADR in the organized program [8], supporting the suitability of our study design despite the unavailability of ADR values before study initiation. In addition, the parallel design is expected to minimize any operator bias, as the endoscopist does not have a second chance to detect any possibly overlooked lesions; this compels the endoscopist to perform an accurate colonoscopy, especially in a FIT-positive patient, where the fear of missing an early CRC is always present. Regarding the end point, ADR has been associated with post-colonoscopy CRC, even in a FIT-positive setting [10] [12] [37]. In addition, the fact that Endocuff Vision increased detection of advanced adenomas in low detectors supports the clinical relevance of our findings.

In a small proportion of cases, Endocuff Vision was removed, mainly for severe diverticulosis, past extensive abdominal surgery, and pain; these may be considered relative contraindications to the use of Endocuff Vision and when possible should be appraised before colonoscopy. Finally, many variables were tested in the secondary analysis; however, as these were tested only for explanatory purposes and secondary outcomes, no correction methods were applied.

In conclusion, our large, multicenter, randomized trial demonstrated the clinical efficacy of Endocuff Vision in an organized FIT-based population program by improving the exploration of the whole colonic mucosa. More studies are needed to determine the specific patient- and endoscopist-related indications for the use of this device.

Competing interests

The authors declare that they have no conflict of interest.

Acknowledgment

This paper is dedicated to the memory of Grazia Grazzini. Her devotion to life, to research, to teamwork, and her enthusiastic professionalism will be forever in our grateful hearts. Goodbye, Grazia!

We thank the EPICLIN staff at CPO Piemonte for their support in the management of the study procedures and database.

^* Deceased

• References

• 1 Atkin WS, Valori R, Kuipers EJ. et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition – Colonoscopic surveillance following adenoma removal. Endoscopy 2012; 44 (Suppl. 03) SE151-163
  Thieme ConnectPubMedSearch in Google Scholar
• 2 Hewitson P, Glasziou P, Watson E. et al. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol 2008; 103: 1541-1549
  CrossrefPubMedSearch in Google Scholar
• 3 von Karsa L, Patnick J, Segnan N. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition – Executive summary. Endoscopy 2012; 44 (Suppl. 03) SE1-8
  PubMedSearch in Google Scholar
• 4 Saftoiu A, Hassan C, Areia M. et al. Role of gastrointestinal endoscopy for the screening of digestive tract cancers in Europe. European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 2020; 52: 293-304
  Thieme ConnectPubMedSearch in Google Scholar
• 5 Schreuders EH, Ruco A, Rabeneck L. et al. Colorectal cancer screening: a global overview of existing programmes. Gut 2015; 64: 1637-1649
  CrossrefPubMedSearch in Google Scholar
• 6 Atkin W, Cross AJ, Kralj-Hans I. et al. Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study. Health Technol Assess 2019; 23: 1-84
  CrossrefPubMedSearch in Google Scholar
• 7 Zorzi M, Hassan C, Capodaglio G. et al. Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test. Gut 2018; 67: 2124-2130
  CrossrefPubMedSearch in Google Scholar
• 8 Zorzi M, Senore C, Da Re F. et al. Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy). Gut 2015; 64: 1389-1396
  CrossrefPubMedSearch in Google Scholar
• 9 Zorzi M, Zappa M. AIRTUM Working Group. Synthetic indicator of the impact of colorectal cancer screening programmes on incidence rates. Gut 2020; 69: 311-316
  CrossrefPubMedSearch in Google Scholar
• 10 Kaminski MF, Regula J, Kraszewska E. et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010; 362: 1795-1803
  CrossrefPubMedSearch in Google Scholar
• 11 Corley DA, Jensen CD, Marks AR. et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014; 370: 1298-1306
  CrossrefPubMedSearch in Google Scholar
• 12 Cubiella J, Castells A, Andreu M. et al. Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs. United Eur Gastroenterol J 2017; 5: 255-260
  CrossrefPubMedSearch in Google Scholar
• 13 Kaminski MF, Thomas-Gibson S, Bugajski M. et al. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy 2017; 49: 378-397
  Thieme ConnectPubMedSearch in Google Scholar
• 14 Inra JA, Nayor J, Rosenblatt M. et al. Comparison of colonoscopy quality measures across various practice settings and the impact of performance scorecards. Dig Dis Sci 2017; 62: 894-902
  CrossrefPubMedSearch in Google Scholar
• 15 le Clercq CMC, Mooi RJ, Winkens B. et al. Temporal trends and variability of colonoscopy performance in a gastroenterology practice. Endoscopy 2016; 48: 248-255
  Thieme ConnectPubMedSearch in Google Scholar
• 16 Hernandez LV, Deas TM, Catalano MF. et al. Longitudinal assessment of colonoscopy quality indicators: a report from the Gastroenterology Practice Management Group. Gastrointest Endosc 2014; 80: 835-841
  CrossrefPubMedSearch in Google Scholar
• 17 Jover R, Zapater P, Polanía E. et al. Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies. Gastrointest Endosc 2013; 77: 381-389
  CrossrefPubMedSearch in Google Scholar
• 18 Rex D, Cutler C, Lemmel G. et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997; 112: 24-28
  CrossrefPubMedSearch in Google Scholar
• 19 Zhao S, Wang S, Pan P. et al. Magnitude, risk factors, and factors associated with adenoma miss rate of tandem colonoscopy: a systematic review and meta-analysis. Gastroenterology 2019; 156: 1661-1674
  CrossrefPubMedSearch in Google Scholar
• 20 Hassan C, Spadaccini M, Iannone A. et al. Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis. Gastrointest Endosc 2021; 93: 77-85
  CrossrefPubMedSearch in Google Scholar
• 21 Repici A, Badalamenti M, Maselli R. et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology 2020; 159: 512-520
  CrossrefPubMedSearch in Google Scholar
• 22 Facciorusso A, Triantafyllou K, Murad MH. et al. Compared abilities of endoscopic techniques to increase colon adenoma detection rates: a network meta-analysis. Clin Gastroenterol Hepatol 2019; 17: 2439-2454
  CrossrefPubMedSearch in Google Scholar
• 23 Jian HX, Feng BC, Zhang Y. et al. EndoCuff-assisted colonoscopy could improve adenoma detection rate: a meta-analysis of randomized controlled trials. J Dig Dis 2019; 20: 578-588
  CrossrefPubMedSearch in Google Scholar
• 24 Thayalasekaran S, Frazzoni L, Antonelli G. et al. Endoscopic technological innovations for neoplasia detection in organized colorectal cancer screening programs: a systematic review and meta-analysis. Gastrointest Endosc 2020; 92: 840-847
  CrossrefPubMedSearch in Google Scholar
• 25 Moher D, Hopewell S, Schulz KF. et al. CONSORT 2010 Explanation and elaboration: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 2010; 63: e1-37
  CrossrefPubMedSearch in Google Scholar
• 26 Lai EJ, Calderwood AH, Doros G. et al. The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009; 69: 620-625
  CrossrefPubMedSearch in Google Scholar
• 27 The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc 2003; 58: S3-43
  CrossrefPubMedSearch in Google Scholar
• 28 Schlemper RJ, Riddell RH, Kato Y. et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000; 47: 251-255
  CrossrefPubMedSearch in Google Scholar
• 29 Cotton PB, Eisen GM, Aabakken L. et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454
  CrossrefPubMedSearch in Google Scholar
• 30 Williet N, Tournier Q, Vernet C. et al. Effect of Endocuff-assisted colonoscopy on adenoma detection rate: meta-analysis of randomized controlled trials. Endoscopy 2018; 50: 846-860
  Thieme ConnectPubMedSearch in Google Scholar
• 31 Zorzi M. The second level survey. XIII National Congress of the Italian Colorectal Screening Group; 2018 October 25–26; Lerici, Italy [in Italian]. www.giscor.it/convegni/giscor-2018/congresso/10_ZORZI.pdf
• 32 Tangri N, Kitsios GD, Su SH. et al. Accounting for center effects in multicenter trials. Epidemiology 2010; 21: 912-913
  CrossrefPubMedSearch in Google Scholar
• 33 Kahan BC. Accounting for centre-effects in multicentre trials with a binary outcome – when, why, and how?. BMC Med Res Methodol 2014; 14: 20
  CrossrefPubMedSearch in Google Scholar
• 34 Kahan BC, Morris TP. Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis. BMJ 2012; 345: e5840
  CrossrefPubMedSearch in Google Scholar
• 35 Ngu WS, Bevan R, Tsiamoulos ZP. et al. Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial. Gut 2019; 68: 280-288
  CrossrefPubMedSearch in Google Scholar
• 36 Bhattacharyya R, Chedgy F, Kandiah K. et al. Endocuff-assisted vs. standard colonoscopy in the fecal occult blood test-based UK Bowel Cancer Screening Programme (E-cap study): a randomized trial. Endoscopy 2017; 49: 1043-1050
  Thieme ConnectPubMedSearch in Google Scholar
• 37 Greuter MJE, de Klerk CM, Meijer GA. et al. Screening for colorectal cancer with fecal immunochemical testing with and without postpolypectomy surveillance colonoscopy: a cost-effectiveness analysis. Ann Intern Med 2017; 167: 544-554
  CrossrefPubMedSearch in Google Scholar

Corresponding author

Publication History

Received: 18 September 2020

Accepted: 01 February 2021

Accepted Manuscript online:
01 February 2021

Article published online:
08 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Atkin WS, Valori R, Kuipers EJ. et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition – Colonoscopic surveillance following adenoma removal. Endoscopy 2012; 44 (Suppl. 03) SE151-163
  Thieme ConnectPubMedSearch in Google Scholar
• 2 Hewitson P, Glasziou P, Watson E. et al. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol 2008; 103: 1541-1549
  CrossrefPubMedSearch in Google Scholar
• 3 von Karsa L, Patnick J, Segnan N. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition – Executive summary. Endoscopy 2012; 44 (Suppl. 03) SE1-8
  PubMedSearch in Google Scholar
• 4 Saftoiu A, Hassan C, Areia M. et al. Role of gastrointestinal endoscopy for the screening of digestive tract cancers in Europe. European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 2020; 52: 293-304
  Thieme ConnectPubMedSearch in Google Scholar
• 5 Schreuders EH, Ruco A, Rabeneck L. et al. Colorectal cancer screening: a global overview of existing programmes. Gut 2015; 64: 1637-1649
  CrossrefPubMedSearch in Google Scholar
• 6 Atkin W, Cross AJ, Kralj-Hans I. et al. Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study. Health Technol Assess 2019; 23: 1-84
  CrossrefPubMedSearch in Google Scholar
• 7 Zorzi M, Hassan C, Capodaglio G. et al. Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test. Gut 2018; 67: 2124-2130
  CrossrefPubMedSearch in Google Scholar
• 8 Zorzi M, Senore C, Da Re F. et al. Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy). Gut 2015; 64: 1389-1396
  CrossrefPubMedSearch in Google Scholar
• 9 Zorzi M, Zappa M. AIRTUM Working Group. Synthetic indicator of the impact of colorectal cancer screening programmes on incidence rates. Gut 2020; 69: 311-316
  CrossrefPubMedSearch in Google Scholar
• 10 Kaminski MF, Regula J, Kraszewska E. et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010; 362: 1795-1803
  CrossrefPubMedSearch in Google Scholar
• 11 Corley DA, Jensen CD, Marks AR. et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014; 370: 1298-1306
  CrossrefPubMedSearch in Google Scholar
• 12 Cubiella J, Castells A, Andreu M. et al. Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs. United Eur Gastroenterol J 2017; 5: 255-260
  CrossrefPubMedSearch in Google Scholar
• 13 Kaminski MF, Thomas-Gibson S, Bugajski M. et al. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy 2017; 49: 378-397
  Thieme ConnectPubMedSearch in Google Scholar
• 14 Inra JA, Nayor J, Rosenblatt M. et al. Comparison of colonoscopy quality measures across various practice settings and the impact of performance scorecards. Dig Dis Sci 2017; 62: 894-902
  CrossrefPubMedSearch in Google Scholar
• 15 le Clercq CMC, Mooi RJ, Winkens B. et al. Temporal trends and variability of colonoscopy performance in a gastroenterology practice. Endoscopy 2016; 48: 248-255
  Thieme ConnectPubMedSearch in Google Scholar
• 16 Hernandez LV, Deas TM, Catalano MF. et al. Longitudinal assessment of colonoscopy quality indicators: a report from the Gastroenterology Practice Management Group. Gastrointest Endosc 2014; 80: 835-841
  CrossrefPubMedSearch in Google Scholar
• 17 Jover R, Zapater P, Polanía E. et al. Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies. Gastrointest Endosc 2013; 77: 381-389
  CrossrefPubMedSearch in Google Scholar
• 18 Rex D, Cutler C, Lemmel G. et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997; 112: 24-28
  CrossrefPubMedSearch in Google Scholar
• 19 Zhao S, Wang S, Pan P. et al. Magnitude, risk factors, and factors associated with adenoma miss rate of tandem colonoscopy: a systematic review and meta-analysis. Gastroenterology 2019; 156: 1661-1674
  CrossrefPubMedSearch in Google Scholar
• 20 Hassan C, Spadaccini M, Iannone A. et al. Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis. Gastrointest Endosc 2021; 93: 77-85
  CrossrefPubMedSearch in Google Scholar
• 21 Repici A, Badalamenti M, Maselli R. et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology 2020; 159: 512-520
  CrossrefPubMedSearch in Google Scholar
• 22 Facciorusso A, Triantafyllou K, Murad MH. et al. Compared abilities of endoscopic techniques to increase colon adenoma detection rates: a network meta-analysis. Clin Gastroenterol Hepatol 2019; 17: 2439-2454
  CrossrefPubMedSearch in Google Scholar
• 23 Jian HX, Feng BC, Zhang Y. et al. EndoCuff-assisted colonoscopy could improve adenoma detection rate: a meta-analysis of randomized controlled trials. J Dig Dis 2019; 20: 578-588
  CrossrefPubMedSearch in Google Scholar
• 24 Thayalasekaran S, Frazzoni L, Antonelli G. et al. Endoscopic technological innovations for neoplasia detection in organized colorectal cancer screening programs: a systematic review and meta-analysis. Gastrointest Endosc 2020; 92: 840-847
  CrossrefPubMedSearch in Google Scholar
• 25 Moher D, Hopewell S, Schulz KF. et al. CONSORT 2010 Explanation and elaboration: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 2010; 63: e1-37
  CrossrefPubMedSearch in Google Scholar
• 26 Lai EJ, Calderwood AH, Doros G. et al. The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009; 69: 620-625
  CrossrefPubMedSearch in Google Scholar
• 27 The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc 2003; 58: S3-43
  CrossrefPubMedSearch in Google Scholar
• 28 Schlemper RJ, Riddell RH, Kato Y. et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000; 47: 251-255
  CrossrefPubMedSearch in Google Scholar
• 29 Cotton PB, Eisen GM, Aabakken L. et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454
  CrossrefPubMedSearch in Google Scholar
• 30 Williet N, Tournier Q, Vernet C. et al. Effect of Endocuff-assisted colonoscopy on adenoma detection rate: meta-analysis of randomized controlled trials. Endoscopy 2018; 50: 846-860
  Thieme ConnectPubMedSearch in Google Scholar
• 31 Zorzi M. The second level survey. XIII National Congress of the Italian Colorectal Screening Group; 2018 October 25–26; Lerici, Italy [in Italian]. www.giscor.it/convegni/giscor-2018/congresso/10_ZORZI.pdf
• 32 Tangri N, Kitsios GD, Su SH. et al. Accounting for center effects in multicenter trials. Epidemiology 2010; 21: 912-913
  CrossrefPubMedSearch in Google Scholar
• 33 Kahan BC. Accounting for centre-effects in multicentre trials with a binary outcome – when, why, and how?. BMC Med Res Methodol 2014; 14: 20
  CrossrefPubMedSearch in Google Scholar
• 34 Kahan BC, Morris TP. Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis. BMJ 2012; 345: e5840
  CrossrefPubMedSearch in Google Scholar
• 35 Ngu WS, Bevan R, Tsiamoulos ZP. et al. Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial. Gut 2019; 68: 280-288
  CrossrefPubMedSearch in Google Scholar
• 36 Bhattacharyya R, Chedgy F, Kandiah K. et al. Endocuff-assisted vs. standard colonoscopy in the fecal occult blood test-based UK Bowel Cancer Screening Programme (E-cap study): a randomized trial. Endoscopy 2017; 49: 1043-1050
  Thieme ConnectPubMedSearch in Google Scholar
• 37 Greuter MJE, de Klerk CM, Meijer GA. et al. Screening for colorectal cancer with fecal immunochemical testing with and without postpolypectomy surveillance colonoscopy: a cost-effectiveness analysis. Ann Intern Med 2017; 167: 544-554
  CrossrefPubMedSearch in Google Scholar

• Supplementary Material