Post-colonoscopy colorectal cancer: A population-based cohort study of fecal occult blood test-positive colonoscopies.

BACKGROUND: Data on post-colonoscopy colorectal cancers (PCCRCs) after fecal occult blood test (FOBT)-positive colonoscopies is scarce (guaiac-based (gFOBT) or fecal immunochemical test (FIT)). AIMS: Evaluate the prevalence and characteristics of PCCRCs in the French gFOBT CRC screening program. METHODS: Retrospective population-based cohort study of all gFOBT-positive colonoscopies performed among individuals aged 50-74 between 2003 and 2014 within the CRC screening program organized in the Haut-Rhin (Alsace, France). The main outcome was PCCRC-3y rate. Adenoma detection rates (ADRs) calculated on gFOBT-positive colonoscopies were compared to those calculated on FIT-positive colonoscopies performed by the same gastroenterologists. RESULTS: Overall, 9106 gFOBT-positive colonoscopies performed by 36 gastroenterologists were included. Sixteen PCCRC-3y and 31 PCCRC-5y were diagnosed (68.8 % and 58.1 % were true interval PCCRCs respectively). The unadjusted PCCRC-3y rate was 2.4 % [95 % confidence interval (CI) 1.4 %-3.9 %]. The risk for PCCRC-5y was significantly higher when the gastroenterologist's ADR was <35 % compared to ≥35 % (HR 2.17 [95 %CI 1.19-3.93]). The mean absolute difference for ADR between gFOBT- and FIT-positive colonoscopies was 16.3 % in favor of FIT-positive colonoscopies. CONCLUSION: PCCRC-3y prevalence was low, estimated at 2.4 %. We suggest that the minimum standard for ADR in gFOBT- and FIT-positive colonoscopies should be set at 35 % and 50 % to 55 % respectively, in the French screening program.

Adenoma detection rate is enough to assess endoscopist performance: a population-based observational study of FIT-positive colonoscopies.

Background and study aims Neoplasia-related indicators, such as adenoma detection rate (ADR), are a priority in the quality improvement process for colonoscopy. Our aim was to assess and compare different detection and characterization indicators in fecal immunochemical test (FIT)-positive colonoscopies, to determine associated factors, and to propose benchmarks. Patients and methods Retrospective analysis of prospectively collected data from all colonoscopies performed between 2015 and 2019 after a positive quantitative FIT in the population-based colorectal cancer screening program conducted in Alsace, part of the French national program. Detection indicators included ADR, mean number of adenomas per colonoscopy, and proximal serrated lesion (SL) detection rate. Characterization indicators included rate of non-neoplastic polyp (NNP) detection. Results Overall, 13,067 FIT-positive colonoscopies were evaluated, performed by 80 community gastroenterologists. The overall ADR was 57.6 %, and a 10 µg/g increase in fecal hemoglobin concentration was significantly associated with higher ADR (odds ratio [95 % confidence interval] = 1.02 [1.02-1.03]). Endoscopists whose ADR was ≥ 55 % were high detectors for all neoplasia, including proximal SLs and number of adenomas. The rate of detection of NNPs was 39.5 % in highest detectors (ADR > 70 %), significantly higher than in lower detectors (21.4 %) ( P  < 0.001). There was a strong correlation between detection and characterization indicators, e. g. between rates of detection of proximal SLs and NNPs (Pearson = 0.73; P  < 0.01). Conclusions A single indicator, ADR, is enough to assess endoscopist performance for both detection and characterization in routine practice provided the minimum target standard is raised and a maximum standard is added: 55 % and 70 % for FIT-positive colonoscopies, respectively.

Colonoscopy may be weak link in organised colorectal cancer screening programme with faecal immunochemical test.

OBJECTIVE: To evaluate the quality of colonoscopies performed after a positive faecal immunochemical test in the French colorectal cancer screening programme. METHODS: Retrospective analysis of all colonoscopies performed between 2015 and 2019 after a positive quantitative faecal immunochemical test in the population-based colorectal cancer screening programme organised in Alsace, part of the French programme. The following indicators were evaluated: annual colonoscopy volume, caecal intubation rate, adenoma detection rate, proximal serrated lesion detection rate and proportion of patients referred directly to surgery for benign polyp management. Endoscopists who performed <30 faecal immunochemical test positive colonoscopies were non-assessable. RESULTS: Overall, 13,455 faecal immunochemical test-positive colonoscopies performed by 116 community gastroenterologists were included, 13,067 of them by 80 assessable endoscopists. The overall caecal intubation, adenoma detection and proximal serrated lesion detection rates were 97.9%, 57.6% and 7.6%, respectively. They were <90%, <45% and <1% for 1.3%, 12.5% and 6.3% of the endoscopists, respectively. Overall, 1028 (7.9%) individuals were examined by 13 low-performing endoscopists and 328 (2.4%) individuals by 33 low-volume non-assessable endoscopists. Among 9133 individuals harbouring polyps, 155 (1.7%) had unwarranted surgery for a benign polyp. Overall, 1487 individuals (11.1%; 95% confidence interval 10.5-11.6) were not given the best possible chances, whereas 5545 individuals (41.2%; 95% confidence interval 40.4-42.0) were offered the best possible chances by 37 endoscopists. CONCLUSIONS: At programme level, the key performance indicators evaluated largely exceeded the target standards. At individual level, at least one in nine individuals was not given the best possible chances during faecal immunochemical test-positive colonoscopies by a minority of poor-performing and/or low-volume endoscopists.

Management of large polyps in a colorectal cancer screening program with fecal immunochemical test: a community- and population-based observational study.

Background and study aims The aim of this study was to analyze presentation, management, and outcomes of large polyps (LPs; ≥ 20 mm) detected in a colorectal cancer (CRC) screening program using a quantitative fecal immunochemical test (FIT). Patients and methods This was a retrospective community- and population-based observational study of all LPs detected in patients aged 50 to 74 years between 2015 and 2019 during FIT-positive colonoscopies within the screening program organized in Alsace (France). Results Among 13,633 FIT-positive colonoscopies, 1256 LPs (8.5 % malignant and 51.8 % nonpedunculated) were detected by 102 community gastroenterologists in 1164 patients (one in 12 colonoscopies). The sensitivity of optical diagnosis of malignancy was 54 % for nonpedunculated and 27 % for pedunculated T1 CRCs. The endoscopic resection rate was 82.7 % (95 % confidence interval [CI] 80.3-84.9) for benign LPs (70.2 % [95 % CI 66.4-74.1]) nonpedunculated, 95.2 % [95 % CI 93.4-97.1] pedunculated), varying from 0 to 100 % depending on the endoscopist. It was correlated with cecal intubation (Pearson r  = 0.49, P  < 0.01) and adenoma detection rates ( r  = 0.25, P  = 0.01). Most endoscopists did not refer patients to more experienced endoscopists, and as a result, 60 % to 90 % of 183 surgeries for benign LPs were unwarranted. Endoscopic resection was curative for 4.3 % (95 % CI 0.9-12.0) of nonpedunculated and 37.8 % (95 % CI 22.5-55.2) of pedunculated T1 CRCs. Overall, 22 endoscopic submucosal dissections had to be performed to avoid one surgery. Conclusions Compared with current recommendations, there is tremendous room for improvement in community endoscopy practices in the diagnosis and management of LPs. Detection and polypectomy competencies are correlated and highly variable among endoscopists. Endoscopic resection is curative for 83 % of benign LPs and 16 % of T1 CRCs.

Adverse events of colonoscopy in a colorectal cancer screening program with fecal immunochemical testing: a population-based observational study.

Background and study aims The aim of this study was to assess adverse events (AEs) associated with colonoscopy in the French colorectal cancer screening program with fecal occult blood test (FOBT). Patients and methods A retrospective cohort study was performed of all colonoscopies performed from 2015 to 2018 for a positive fecal immunochemical test (FIT) in patients aged 50 to 74 years within the screening program in progress in Alsace, part of the French program. AEs were recorded through prospective voluntary reporting by community gastroenterologists and retrospective postal surveys addressed to individuals screened. They were compared with those recorded in the previous program following colonoscopies performed from 2003 to 2014 for a positive guaiac-based FOBT (gFOBT). Results Of 9576 colonoscopies performed for a positive FIT, 6194 (64.7 %) were therapeutic. Overall, 180 AEs were recorded (18.8 ‰, 95 % CI 16.1-21.5), 114 of them (11.9 ‰, 95 % CI 9.7-14.1) requiring hospitalization, 55 (5.7‰, 95 % CI 4.2-7.3) hospitalization > 24 hours, and eight (0.8 ‰, 95 % CI 0.3-1.4) surgery. The main complications requiring hospitalization were perforation (n = 18, 1.9 ‰, 95 % CI 1.0-2.7) and bleeding (n = 31, 3.2 ‰, 95 % CI 2.1-4.4). Despite a significant increase in several risk factors for complication, the rate of AEs remained stable between gFOBT and FIT programs. Overall, we observed one death (1/27,000 colonoscopies) and three splenic injuries. Conclusions The harms of colonoscopy in a colorectal cancer screening program with FIT are more frequent than usually estimated. This study revealed six AEs requiring hospitalization > 24 hours (three bleeds, two perforations), one necessitating surgery, and 50 minor complications per 1000 colonoscopies.

Participation in four rounds of a French colorectal cancer screening programme with guaiac faecal occult blood test: a population-based open cohort study.

OBJECTIVES: Four randomized controlled trials have demonstrated the efficacy of screening using a guaiac faecal occult blood test (gFOBT) on colorectal cancer (CRC) mortality. Whether their results are transposable to the real world is unknown. This study aimed to assess the determinants of participation in the first four rounds of the CRC screening programme using a gFOBT implemented since 2003 in the Haut-Rhin (Alsace) part of the French national programme. METHODS: We performed a population-based open cohort study of all residents aged 50-74, around 200,000 people. They were invited by mail to participate every other year. The gFOBT kits (Hemoccult II) were first provided by general practitioners, and then directly mailed to persons who failed to comply. RESULTS: The uptake decreased significantly across all rounds, from 54.3% to 47.1% (p < 0.0001), mainly in people younger than 60. The proportion of people screened by general practitioners increased significantly from 77.0% in the first round to 84.2% in the fourth (p < 0.01). Overall, 61.3% of the invited population participated at least once, and 14.3% had completed all the four tests. The colonoscopy uptake was around 91%, among the highest ever reported. CONCLUSIONS: Despite the involvement of general practitioners, the uptake and adherence to repeat testing are modest and deteriorate with time, so that the reduction in CRC mortality in reality will be significantly lower than that in the trials. The benefit-risk balance of the French programme is, at present, less favourable than that shown in the trials.

The mean number of adenomas per procedure should become the gold standard to measure the neoplasia yield of colonoscopy: a population-based cohort study.

BACKGROUND: Measuring adenoma detection is a priority in the quality improvement process for colonoscopy. Our aim was (1) to determine the most appropriate quality indicators to assess the neoplasia yield of colonoscopy and (2) to establish benchmark rates for the French colorectal cancer screening programme. METHODS: Retrospective study of all colonoscopies performed in average-risk asymptomatic people aged 50-74 years after a positive guaiac faecal occult blood test in eight administrative areas of the French population-based programme. RESULTS: We analysed 42,817 colonoscopies performed by 316 gastroenterologists. Endoscopists who had an adenoma detection rate around the benchmark of 35% had a mean number of adenomas per colonoscopy varying between 0.36 and 0.98. 13.9% of endoscopists had a mean number of adenomas above the benchmark of 0.6 and an adenoma detection rate below the benchmark of 35%, or inversely. Correlation was excellent between mean numbers of adenomas and polyps per colonoscopy (Pearson coefficient r=0.90, p<0.0001), better than correlation between mean number of adenomas and adenoma detection rate (r=0.84, p=0.01). CONCLUSION: The mean number of adenomas per procedure should become the gold standard to measure the neoplasia yield of colonoscopy. Benchmark could be established at 0.6 in the French programme.

Harms of colonoscopy in a colorectal cancer screening programme with faecal occult blood test: a population-based cohort study.

BACKGROUND AND AIMS: To assess the harms of colonoscopy in a real world colorectal cancer screening programme with faecal occult blood test. METHODS: Retrospective cohort study of all colonoscopies performed in patients aged 50-74 for a positive guaiac-based faecal occult blood test between September 2003 and February 2010 within the screening programme in progress in Alsace (France). Adverse events were recorded through prospective voluntary reporting by gastroenterologists and retrospective postal surveys addressed to persons screened and their general practitioners. RESULTS: Of 10,277 colonoscopies, 250 adverse events were recorded, 48 (4.7 ‰, 95% CI 3.4-6.0) of them being moderate or severe, mainly 10 (1.0 ‰, 95% CI 0.4-1.6) perforations and 31 (3.0 ‰, 95% CI 2.0-4.1) bleeding. 91.7% of moderate and severe adverse events were the result of a therapeutic procedure. Of 103 serious adverse events, eight (7.8%) were considered preventable. Gastroenterologists reported 52.2% of moderate and severe adverse events. A mild adverse event or an incident was reported in up to 97.0 ‰ (95% CI 83.2-110.7) colonoscopies. CONCLUSION: The harms of colonoscopy were underestimated in all randomized controlled trials on colorectal cancer screening with faecal occult blood test. They are greater in a real world programme, estimated at 7.5 major and 100 minor adverse events per 1000 colonoscopies.

Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme.

BACKGROUND: Immunochemical faecal occult blood tests have greater sensitivity for colorectal cancer screening than guaiac-based tests; however the number of positive tests required is still under discussion. METHODS: A direct comparison of Hemoccult II with two immunochemical quantitative tests (OC-Sensor and FOB-Gold) using a 2-sample strategy was performed in over 30,000 patients undergoing colorectal cancer screening in France. RESULTS: Positivity ratio between immunochemical tests and Hemoccult II varied between 2.2 (OC-Sensor) and 2.4 (FOB-Gold) for the lowest cut-off value and 1.5-1.4 for the highest cut-off value. The positive predictive value for colorectal cancer was similar for immunochemical tests and Hemoccult II, and significantly higher for immunochemical tests for advanced adenomas. The detection rate of both colorectal cancer and advanced adenomas was higher with immunochemical tests than with Hemoccult II. With the 2-sample strategy and the lowest cut-off value the detection rate of colorectal cancer almost doubled and for advanced adenomas quadrupled. CONCLUSION: For colorectal cancer screening with immunochemical faecal occult blood tests, an acceptable strategy would be 2-day sampling with at least one positive test at a cut-off between 150 and 200 ng/mL (OC-Sensor) and 176 and 234 ng/mL (FOB-Gold). Data on the ease of test interpretation and cost-effectiveness now necessary to make definitive choices.

Measurement of adenoma detection and discrimination during colonoscopy in routine practice: an exploratory study.

BACKGROUND: Measuring neoplasia yield is a priority in the quality improvement process for colonoscopy. However, neither the most appropriate quality indicator nor the standard threshold has been established. OBJECTIVE: To determine the most appropriate quality indicators to assess the yield of routine colonoscopy. DESIGN: Retrospective. SETTING: Population-based colorectal cancer screening program in 3 French administrative areas. SUBJECTS: One hundred gastroenterologists and their average-risk asymptomatic patients aged 50 to 74 years undergoing colonoscopy for positive guaiac-based fecal occult blood test results. MAIN OUTCOME MEASUREMENTS: Comparison of several indicators, mainly the adenoma detection rate (ADR) and polyp detection rate (PDR), the mean number of adenomas per colonoscopy (MNA) and mean number of polyps (MNP) and the proportion of adenomas among polyps (PAP). RESULTS: Correlations were good between the ADR and PDR (Pearson coefficient r = 0.88 [95% CI, 0.78-0.94]) and between MNA and MNP (r = 0.89 [95% CI, 0.79-0.94]) (P < .0001 for both). Gastroenterologists were classified as higher or lower detectors in comparison with the lower limit of the 95% confidence interval of the median value for each indicator. The MNP (MNA) provided better discrimination than the PDR (ADR). Concordance between classifications of gastroenterologists according to their MNA and MNP was excellent (κ = 0.89). PAP varied dramatically from 38% to 95% between gastroenterologists and was very poorly correlated with the ADR (r = -0.27 [95% CI, -0.54 to 0.07; P = .11]) and the MNA (r = 0.03 [95% CI, -0.29 to 0.36; P = .88]). LIMITATIONS: Some factors influencing the neoplasia yield were not taken into account. CONCLUSIONS: The MNP could replace the ADR for the assessment of adenoma detection in routine practice. A separate indicator, PAP, would be necessary to assess adenoma discrimination ability.

Diagnostic accuracy of community pathologists in the interpretation of colorectal polyps.

BACKGROUND AND AIMS: Management of patients with endoscopically removed colorectal polyps is generally dependent on pathological evaluation. The aim of this study was to assess the accuracy and clinical impact of pathologic interpretation of colorectal polyps by community pathologists. METHODS: Two expert gastrointestinal pathologists reviewed the slides of 300 colorectal polyps initially examined by 14 general pathologists. Polyps had been detected by a fecal occult blood test colorectal cancer screening program in Haut-Rhin, a French administrative district. RESULTS: Villous histology was overread in 24.8% of cases and high-grade dysplasia in 22.0%. The diagnosis of serrated adenoma was confirmed in 15.7% of cases. The diagnosis of T1 carcinoma was overestimated in seven cases (17.9%) and missed in four. In the screening program, the proportion of correct diagnoses of community pathologists was estimated at 45.3% of polyps, of misclassification without clinical impact at 27.5%, and of misclassification with a theoretical impact on management at 27.2%, leading to over-surveillance in 20.3% of polyps and to unnecessary surgical resection in three individuals. Overall, 37.5% of the pathology reports of malignant polyps were complete, presenting all criteria necessary for therapeutic decision-making. CONCLUSION: Community pathologists exhibited moderate accuracy for interpreting colorectal polyps, with an impact on patient management for around one out of five individuals. Our results confirm the intrinsic poor reliability of the pathologic interpretation of villous histology and high-grade dysplasia and suggest that these advanced pathologic features should be abandoned for clinical use. They illustrate the need for a clarification of the nomenclature of serrated polyps.

Short term outcomes of the first round of a pilot colorectal cancer screening programme with guaiac based faecal occult blood test.

OBJECTIVE: To assess both feasibility and short term outcomes of a population based colorectal cancer screening programme using a biennial guaiac based faecal occult blood test (gFOBT). METHOD: All participants were invited by mail to take part in a screening programme using a non-rehydrated gFOBT. The gFOBTs were first provided by general practitioners (GPs) and then directly mailed to individuals who failed to comply after two invitations. The setting was a French administrative district: Haut-Rhin (710,000 inhabitants). 182,981 residents aged 50-74 years were invited to participate. RESULTS: 19,274 people (10.5%) were excluded from gFOBT screening and 90,706 completed a gFOBT, so that the participation rate was 55.4% of those eligible. 76.5% of the completed gFOBTs were provided by GPs and 15.5% by direct mailing. The gFOBT positivity rate was 3.4%. The positive predictive value was 42.7% for neoplasia (women 30.8%, men 52.5%), 23.6% for advanced adenoma, and 7.6% for cancer. The number of normal colonoscopic procedures (without neoplasia) needed to be performed for each colonoscopy detecting an advanced neoplasia was 1.8, lower in men (1.2) than in women (3.4), and decreasing with age. Detection rates for neoplasia and cancer were 12.8 and 2.3 per 1000 people screened. 206 adenocarcinomas were detected: 47.6% were stage I and 23.8% stage II. The direct cost was estimated at euro 29.3 per screened person and euro 13,466 per cancer detected. CONCLUSIONS: Participation and diagnostic yield of controlled trials of gFOBT screening are reproducible in the real world at an acceptable cost through an organised population based programme involving GPs.

Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects.

BACKGROUND: Sleep disturbances are frequently encountered in alcohol-dependent patients. Drugs improving sleep during abstinence from alcohol may play an important role in the recovery process. METHODS: In the present study, the effects of acamprosate, a drug successfully used in maintaining abstinence following alcohol withdrawal, were assessed by polysomnographic recordings. A parallel double-blind placebo-controlled study was conducted in 24 male DSM-IV alcohol-dependent subjects aged 35.9+/-1.2 years. Treatments (2 tablets of 333 mg acamprosate vs placebo t.i.d.) were initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Polysomnographic assessments were recorded during acute withdrawal (the first 2 nights following withdrawal) and during postwithdrawal abstinence (the last 2 nights of the trial). RESULTS: Results show that, compared with placebo, acamprosate decreased wake time after sleep onset and increased stage 3 and REM sleep latency (all treatment effects with a p < 0.05 significance). Withdrawal effects themselves were also demonstrated as sleep efficiency (p < 0.01) and total sleep time (p < 0.05) were lower in abstinence nights versus withdrawal nights, whereas no significant treatment x withdrawal effect could be evidenced. Acamprosate was well tolerated during the entire course of the study. CONCLUSIONS: The present study shows that acamprosate ameliorates both sleep continuity and sleep architecture parameters classically described as disturbed in alcohol-dependent patients. From a clinical perspective, it suggests that an 8-day acamprosate prewithdrawal treatment is well tolerated and can attenuate the sleep disturbances engendered by alcohol withdrawal in alcohol-dependent subjects.