Michal F. Kaminski

Quality Indicators for Colonoscopy and the Risk of Interval Cancer

BACKGROUND Although rates of detection of adenomatous lesions (tumors or polyps) and cecal intubation are recommended for use as quality indicators for screening colonoscopy, these measurements have not been validated, and their importance remains uncertain. METHODS We used a multivariate Cox proportional-hazards regression model to evaluate the influence of quality indicators for colonoscopy on the risk of interval cancer. Data were collected from 186 endoscopists who were involved in a colonoscopy-based colorectal-cancer screening program involving 45,026 subjects. Interval cancer was defined as colorectal adenocarcinoma that was diagnosed between the time of screening colonoscopy and the scheduled time of surveillance colonoscopy. We derived data on quality indicators for colonoscopy from the screening programs database and data on interval cancers from cancer registries. The primary aim of the study was to assess the association between quality indicators for colonoscopy and the risk of interval cancer. RESULTS A total of 42 interval colorectal cancers were identified during a period of 188,788 person-years. The endoscopists rate of detection of adenomas was significantly associated with the risk of interval colorectal cancer (P=0.008), whereas the rate of cecal intubation was not significantly associated with this risk (P=0.50). The hazard ratios for adenoma detection rates of less than 11.0%, 11.0 to 14.9%, and 15.0 to 19.9%, as compared with a rate of 20.0% or higher, were 10.94 (95% confidence interval [CI], 1.37 to 87.01), 10.75 (95% CI, 1.36 to 85.06), and 12.50 (95% CI, 1.51 to 103.43), respectively (P=0.02 for all comparisons). CONCLUSIONS The adenoma detection rate is an independent predictor of the risk of interval colorectal cancer after screening colonoscopy.

Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

BACKGROUND AND AIM This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for colonoscopy. METHODS This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. RESULTS The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4 L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2 L PEG plus ascorbate or of sodium picosulphate plus magnesium citrate may be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).

Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

MAIN RECOMMENDATIONS 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % - 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). CONCLUSION Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy

Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies.

Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have identified quality of endoscopy as a major priority and we described our rationale for this in a first manuscript that also addressed the methodology of the quality initiative process.1 The identification of upper gastrointestinal (UGI) performance measures presents a considerable challenge, in contrast to the situation with colonoscopy for instance, where several performance measures (inspection time, adenoma detection rate, and interval cancers, among others) have been identified over the last decade.2,3 Following the Quality in UGI Endoscopy meeting held in Lisbon in 2013, it was clear that there was a need to identify performance measures for the UGI tract, and that quality standards could be identified although there is a paucity of evidence. This lack of evidence helps however to identify research priorities for the development of clinical trials that will further validate and substantiate the implementation of performance measures. The aim therefore of the UGI working group was twofold: (a) to identify performance measures for UGI endoscopy; (b) to identify the evidence or absence of evidence that would develop the research priorities in this field. We used an innovative methodology to facilitate the quality initiative process, which combined a thorough search and standardized evaluation of the available evidence for each clinical question, followed by a Delphi process (http://is.njit.edu/pubs/delphibook/delphibook.pdf) using an online platform.4,5 This online platform permitted iterative rounds of modification and comment by all members of the UGI working group until agreement was reached on the performance measure. We now report these newly identified performance measures.

Population-Based Colonoscopy Screening for Colorectal Cancer: A Randomized Clinical Trial

IMPORTANCE Although some countries have implemented widespread colonoscopy screening, most European countries have not introduced it because of uncertainty regarding participation rates, procedure-related pain and discomfort, endoscopist performance, and effectiveness. To our knowledge, no randomized trials on colonoscopy screening currently exist. OBJECTIVE To investigate participation rate, adenoma yield, performance, and adverse events of population-based colonoscopy screening in several European countries. DESIGN, SETTING, AND POPULATION A population-based randomized clinical trial was conducted among 94 959 men and women aged 55 to 64 years of average risk for colon cancer in Poland, Norway, the Netherlands, and Sweden from June 8, 2009, to June 23, 2014. INTERVENTIONS Colonoscopy screening or no screening. MAIN OUTCOMES AND MEASURES Participation in colonoscopy screening, cancer and adenoma yield, and participant experience. Study outcomes were compared by country and endoscopist. RESULTS Of 31 420 eligible participants randomized to the colonoscopy group, 12 574 (40.0%) underwent screening. Participation rates were 60.7% in Norway (5354 of 8816), 39.8% in Sweden (486 of 1222), 33.0% in Poland (6004 of 18 188), and 22.9% in the Netherlands (730 of 3194) (P < .001). The cecum intubation rate was 97.2% (12 217 of 12 574), with 9726 participants (77.4%) not receiving sedation. Of the 12 574 participants undergoing colonoscopy screening, we observed 1 perforation (0.01%), 2 postpolypectomy serosal burns (0.02%), and 18 cases of bleeding owing to polypectomy (0.14%). Sixty-two individuals (0.5%) were diagnosed with colorectal cancer and 3861 (30.7%) had adenomas, of which 1304 (10.4%) were high-risk adenomas. Detection rates were similar in the proximal and distal colon. Performance differed significantly between endoscopists; recommended benchmarks for cecal intubation (95%) and adenoma detection (25%) were not met by 6 (17.1%) and 10 of 35 endoscopists (28.6%), respectively. Moderate or severe abdominal pain after colonoscopy was reported by 601 of 3611 participants (16.7%) examined with standard air insufflation vs 214 of 5144 participants (4.2%) examined with carbon dioxide (CO2) insufflation (P < .001). CONCLUSIONS AND RELEVANCE Colonoscopy screening entails high detection rates in the proximal and distal colon. Participation rates and endoscopist performance vary significantly. Postprocedure abdominal pain is common with standard air insufflation and can be significantly reduced by using CO2. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00883792.

Leadership training to improve adenoma detection rate in screening colonoscopy: a randomised trial

Objective Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared the effect of leadership training versus feedback only on colonoscopy quality in a countrywide randomised trial. Design 40 colonoscopy screening centres with suboptimal performance in the Polish screening programme (centre leader ADR ≤25% during preintervention phase January to December 2011) were randomised to either a Train-Colonoscopy-Leaders (TCLs) programme (assessment, hands-on training, post-training feedback) or feedback only (individual quality measures). Colonoscopies performed June to December 2012 (early postintervention) and January to December 2013 (late postintervention) were used to calculate changes in quality measures. Primary outcome was change in leaders’ ADR. Mixed effect models using ORs and 95% CIs were computed. Results The study included 24 582 colonoscopies performed by 38 leaders and 56 617 colonoscopies performed by 138 endoscopists at the participating centres. The absolute difference between the TCL and feedback groups in mean ADR improvement of leaders was 7.1% and 4.2% in early and late postintervention phases, respectively. The TCL group had larger improvement in ADR in early (OR 1.61; 95% CI 1.29 to 2.01; p<0.001) and late (OR 1.35; 95% CI 1.10 to 1.66; p=0.004) postintervention phases. In the late postintervention phase, the absolute difference between the TCL and feedback groups in mean ADR improvement of entire centres was 3.9% (OR 1.25; 95% CI 1.04 to 1.50; p=0.017). Conclusions Teaching centre leaders in colonoscopy training improved important quality measures in screening colonoscopy. Trial registration number NCT01667198.

Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview

Objective The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. Methods Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age–sex–standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. Results Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426–205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. Conclusions The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.

Rationale and design of the European Polyp Surveillance (EPoS) trials.

BACKGROUND Current guidelines recommend surveillance colonoscopies after polyp removal depending on the number and characteristics of polyps, but there is a lack of evidence supporting the recommendations. This report outlines the rationale and design of two randomized trials and one observational study investigating evidence-based surveillance strategies following polyp removal. Study design and endpoints: The EPoS studies started to recruit patients in April 2015. EPoS study I randomizes 13 746 patients with low-risk adenomas (1 - 2 tubular adenomas size < 10 mm, low-grade dysplasia) to surveillance after 5 and 10 years, or 10 years only. EPoS study II randomizes 13 704 patients with high-risk adenomas (3 - 10 adenomas or adenoma ≥ 10 mm in diameter, or adenoma with high-grade dysplasia, or > 25 % villous features) to surveillance after 3, 5, and 10 years, or 5 and 10 years only. EPoS study III offers surveillance after 5 and 10 years to patients with serrated polyps ≥ 10 mm in diameter at any location, or serrated polyps ≥ 5 mm in diameter proximal to the splenic flexure. All polyps are removed before patients enter the trials. The primary end point is colorectal cancer incidence after 10 years. We assume a colorectal cancer risk of 1 % for patients in EPoS I, and 2 % for patients in EPoS II. Using a noninferiority hypothesis with an equivalence interval of 0.5 % for EPoS I and 0.7 % for EPoS II, the trials are 90 % powered to uncover differences larger than the equivalence intervals. For EPoS III, no power analyses have been performed. CONCLUSIONS The present trials aim to develop evidence-based strategies for polyp surveillance, thereby maximizing effectiveness and minimizing resources. TRIAL REGISTRATION ClinicalTrials.gov (NCT02319928).

Water exchange versus carbon dioxide insufflation in unsedated colonoscopy: A multicenter randomized controlled trial

BACKGROUND AND STUDY AIMS Compared with air insufflation, water exchange and carbon dioxide (CO2) insufflation have been shown to reduce colonoscopy discomfort; however, head-to-head studies of the two methods are lacking. We aimed to compare water exchange and CO2 insufflation directly with regard to pain during primary unsedated colonoscopy. METHODS Patients willing to undergo unsedated colonoscopy at three centers in Norway and Poland were randomized 1:1 to water exchange or CO2 insufflation during colonoscope insertion. Patients were blinded to group allocation. The primary end point was the proportion of patients reporting moderate or severe procedural pain on a 4-point verbal rating scale (VRS-4) at discharge. Secondary outcomes included the proportion of patients reporting no pain on the VRS-4. RESULTS A total of 473 patients were randomized. A discharge pain questionnaire was completed by 226 of 234 patients (97 %) in the water exchange group versus 226 of 239 patients (95 %) in the CO2 group (P = 0.37). Moderate or severe pain was reported by 47 of 226 patients (21 %) in the water exchange group versus 60 of 226 patients (27 %) in the CO2 group (P = 0.15). No pain was reported by 100 of 226 patients (44 %) and 69 of 226 patients (31 %) in the water exchange and CO2 groups, respectively (P = 0.003). On-demand sedation was used in 15 patients (6 %) in each group (P = 0.95). CONCLUSIONS There was no significant reduction in moderate or severe pain in a comparison of water exchange with CO2 insufflation. The secondary outcome of no pain was significantly more frequent in the water exchange group. Clinical trials registry number: NCT01633333.