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.

[Risk and protective factors for colorectal cancer]. / Facteurs de risque et de protection du cancer colorectal.

RISK AND PROTECTIVE FACTORS FOR COLORECTAL CANCER Behaviour and environment play a more important role than heredity in colorectal carcinogenesis. The proportion of colorectal cancers (CRCs) attributable to occupational exposure, pollution or poor socio- economic status is low. The risk levels on which the French CRC screening recommendations are based are obsolete and need to be updated. An individual with one or two non-advanced adenomas resected at colonoscopy is at low risk of CRC. Only a first-degree family history of CRC in one parent before age 50 or in two parents at any age confers a significant increased risk. Certain diseases or situations that are sources of an increased risk of CRC were not previously considered: cystic fibrosis, radiotherapy and paediatric cancer survivors. New inherited predisposition syndromes associated with a very high risk of CRC have been described in addition to Lynch syndrome and familial adenomatous polyposis: MUTYH-associated polyposis, constitutional MMR deficiency, Lynch-like, PPAP and X syndromes. Half of all CRCs are related to modifiable risk factors associated with westernized lifestyle such as physical inactivity, junk food and obesity. There is nothing specific about dietary recommendations for the primary prevention of CRC: physical activity, limitation of red and processed meat, increase in dietary fibre and dairy products, limitation of alcohol and avoidance of tobacco. Finally, it is premature to use aspirin in primary prevention of CRC outside of Lynch syndrome and associated significant cardiovascular risk.

FACTEURS DE RISQUE ET DE PROTECTION DU CANCER COLORECTAL Comportement et environnement jouent un rôle plus important que l'hérédité dans la carcinogenèse colorectale. La part des cancers colorectaux (CCR) attribuable à une exposition professionnelle, à la pollution ou à un statut socio-économique défavorable est faible. Les niveaux de risque sur lesquels reposent les recommandations françaises de dépistage du CCR sont obsolètes et doivent être actualisés. Un individu ayant un ou deux adénomes non avancés réséqués lors d'une coloscopie est à risque faible de CCR. Seuls les antécédents familiaux au 1er degré de CCR chez un parent avant 50 ans ou chez deux parents quel que soit l'âge confèrent un surrisque significatif. Certaines maladies ou situations sources d'un sur-risque de CCR n'étaient pas prises en compte précédemment : mucoviscidose, radiothérapie et survivant de cancer pédiatrique. De nouveaux syndromes de prédisposition héréditaire associés à un risque très élevé de CCR ont été décrits en sus du syndrome de Lynch et de la polypose adénomateuse familiale : polypose associée à MUTYH, syndromes de déficience constitutionnelle du système MMR, Lynch-like, PPAP et X. La moitié des CCR sont liés à des facteurs de risque modifiables associés au mode de vie occidental tels que sédentarité, malbouffe et obésité. Les recommandations hygiéno-diététiques destinées à la prévention primaire du CCR n'ont rien de spécifique : activité physique, limitation des viandes rouges et charcuteries, augmentation des fibres alimentaires et produits laitiers, limitation de l'alcool et éviction du tabac. Enfin, il est prématuré d'utiliser l'aspirine en prévention primaire du CCR en dehors du syndrome de Lynch et d'un risque cardiovasculaire significatif associé.

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.

[In current practice, what is the best test to detect blood in the stool ?] / En pratique courante, quel est le meilleur test pour rechercher du sang dans les selles ?

"In current practice, what is the best test to detect the presence of blood in faeces? Testing for the presence of blood in faeces is still widely performed in France, although the uptake in the national colorectal cancer screening programme is less than desirable, as is use in routine practice to guide diagnosis when patients present with gastrointestinal or general symptoms. Guaiac-based tests (Hemoccult) are obsolete and have been replaced by faecal immunochemical tests (FITs), both quantitative (OC-Sensor), currently reserved for the screening programme, and qualitative, performed by all medical laboratories. However, qualitative FITs should be abandoned: their visual reading is subjective, their positivity rate is highly variable, around 50%, and their diagnostic sensitivity for colorectal cancer has not been well determined. In contrast, quantitative FITs are reliable and their performance has been well evaluated. Several neighbouring countries use these tests in general practice to assess the risk of colorectal cancer in symptomatic patients and to determine the indication for colonoscopy. In this context, the decision thresholds are very different from those of organised screening: a faecal haemoglobin concentration below 4-10 µg/g is associated with a very low risk of cancer, a concentration above 4-10 µg/g should be investigated by colonoscopy, and a concentration above 150 µg/g requires an urgent colonoscopy."

"En pratique courante, quel est le meilleur test pour rechercher du sang dans les selles ? La recherche de sang dans les selles, malgré son caractère quelque peu désuet, est, à juste titre, encore très prescrite en France, insuffisamment dans le programme national de dépistage organisé du cancer colorectal et en pratique courante pour guider une conduite diagnostique en cas de symptômes digestifs ou généraux. Les tests au gaïac (Hemoccult), obsolètes, ont été remplacés par des tests immunochimiques, quantitatifs (OC-Sensor) réservés au programme de dépistage, et qualitatifs réalisés par tous les laboratoires de biologie médicale. Pourtant les tests qualitatifs sont obsolètes et devraient être abandonnés : leur lecture est subjective, leur taux de positivité très variable, proche de 50 %, et leur sensibilité diagnostique pour le cancer colorectal non évaluée. Au contraire, les tests quantitatifs sont fiables et leurs performances parfaitement évaluées. Plusieurs pays voisins utilisent ces tests en médecine générale pour évaluer le risque de cancer colorectal chez les patients symptomatiques et poser l'indication d'une coloscopie. Dans ce contexte, les seuils décisionnels sont très différents de ceux du dépistage organisé : un taux d'hémoglobine fécale inférieur à 4-10 µg/g de selles est associé à un risque infime de cancer, un taux supérieur à 4-10 µg/g doit être exploré par coloscopie, et un taux supérieur à 150 µg/g relève d'une coloscopie urgente."

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.

Case report of abdominal left upper quadrant collection secondary to fish bone perforation.

We present an unusual case of an intra-abdominal collection which evidenced a rare etiology and raises diagnostic particularities. BACKGROUND: Fish bones ingestion is frequent, but seldom followed by complications. Those are often reported at specific sites. OBJECTIVES: This case report emphasizes the unusual presentation and site localization of a colonic perforation by a small fish bone, in the context of limited radiological accuracy at the diagnostic phase. CASE PRESENTATION: A 37 year old male was admitted to the gastroenterology ward with upper and left sided abdominal pain associated with fever and marked fatigue. His medical history was marked by a sleeve gastrectomy in 2010 for obesity. Abdominal signs and elevated acute inflammatory syndrome on blood tests were followed by computer tomography which revealed a pericolic mass near the left splenic flexure. The pain and fever increased in intensity, so a laparotomy was proposed. Intraoperatively, a tumor-like lesion was found and a resection with oncologic limits was performed. Microscopic examination of the specimen revealed a fish bone, but only after surgery did the patient confirm that he had eaten fish meal the week before. The post-operative period was uneventful. CONCLUSION: Fish bones remain some of the most frequently ingested alimentary foreign bodies; they may cause atypical clinical presentations, frequently omitted by the patients themselves if symptoms appear delayed. They could also lead to possible high-risk complications which need to be addressed by surgeons.

Impact of the COVID-19 pandemic on gastrointestinal endoscopy activity in France.

BACKGROUND: The SARS-CoV-2 pandemic has majorly affected medical activity around the world. We sought to measure the impact of the COVID-19 pandemic on gastrointestinal (GI) endoscopy activity in France. METHODS: We performed a web-based survey, including 35 questions on the responders and their endoscopic practice, from 23 March to 27 March 2020, sent to the 3300 French gastroenterologists practicing endoscopy. RESULTS: 694 GI endoscopists (21 %) provided analyzable data; of these, 29.4 % (204/694) were involved in the management of COVID-19 patients outside the endoscopy department. During the study period, 98.7 % (685/694) of endoscopists had had to cancel procedures. There were 89 gastroenterologists (12.8 %) who reported symptoms compatible with COVID-19 infection, and a positive PCR test was recorded in 12/197 (6.1 %) vs. 3/497 (0.6 %) endoscopists in the high vs. low prevalence areas, respectively (P < 0.001). CONCLUSIONS: The COVID-19 pandemic led to a major reduction in the volume of GI endoscopies performed in France in March 2020. The prolonged limited access to GI endoscopy could lead to a delay in the management of patients with GI cancers.

Quality of life and cost of strategies of two chemotherapy lines in metastatic colorectal cancer: results of the FFCD 2000-05 trial.

Objectives: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). Methods: Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation. Valuations were made using 2009 and 2016 tariffs. QoL was assessed using the QLQ-C30 questionnaire and clinically significant variations were searched. Results: In 2009, the mean cost per patient was significantly lower for the sequential strategy compared to the combination strategy (18,061€ and 23,119€, p = 0.001). In 2016, the difference was no longer significant (16,876€ and 18,090€, p = 0.41) because oxaliplatin and irinotecan became generics. The QoL analysis (292 patients) showed that there was significantly less improvement of global health status in the sequential strategy than in the combination strategy (29% and 42%; p = 0.02) during first-line therapy. No significant differences were observed for emotional functioning (p = 0.45) and physical functioning (p = 0.07) or during second-line therapy. Conclusion: The choice to treat patients with advanced colorectal cancer using one or the other strategy cannot be based on costs or QoL.

Impact of subsequent screening episodes on the positive predictive value for advanced neoplasia and on the distribution of anatomic subsites of colorectal cancer: A population-based study on behalf of the French colorectal cancer screening program.

BACKGROUND: The anatomic distribution of advanced colorectal neoplasia is increasingly important for choosing screening strategies and treatment options. We sought to evaluate the impact of repeated screening on the positive predictive value (PPV) for advanced colorectal neoplasia (advanced adenoma, AA, and colorectal cancer, CRC) and their distribution according to anatomic subsite distribution in average-risk adults. METHOD: The study included 98,031 men and women aged 50-74 who had a positive g-FOBT in 2010 and 2011 and underwent total colonoscopy. The PPV for detection of AA and CRC and the relative risks were determined with log-binomial models, and the distribution of anatomic subsites was estimated according to screening history. RESULT: The median age was 61 years (62 years for participants with AA and 64 for those with CRC). The PPV for detection of advanced neoplasia was 24.5%, substantially higher in men than women (30.7% vs 17.7%), and it increased with age. It also fell at all screening episodes after the first. Subsequent screening episodes were associated with an increased RR for proximal AA (RR 1.13, 95% CI 1.16-1.20). Advancing age (RR 1.28, 95% CI 1.19-1.39 for every 10-year increase in age), female gender (RR 1.31, 95% CI 1.19-1.44), and subsequent screening (RR 1.15, 95% CI 1.04-1.27) were significantly and independently associated with detection of proximal adenocarcinoma. The latter was also detected at an advanced stage more often (RR, 1.24, 95% CI: 1.09-1.42). Early stages of invasive adenocarcinoma (stages I and II) was more likely to be detected in a subsequent than an initial screening (RR 1.07, 95% CI 1.01-1.13). CONCLUSION: This study found that subsequent screening episodes using g-FOBT were associated with an increase in the detection rate of proximal AA and CRC, especially among women. The more frequent detection of proximal invasive adenocarcinoma at an advanced stage in subsequent screenings suggests that some of these tumors may well not be real incident lesions, but are likely to include lesions that were missed on the previous screens. Although modest, the increase in the rate of detection of invasive adenocarcinoma at early (and more curable) stages from the first to subsequent screenings, together with this potential for missed diagnoses on initial screening and the increased detection rate for proximal or rectal AA in subsequent screening episodes, underlines the need to reinforce the population's awareness of the importance of regular consistent screening, after negative results.

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.

Predictive factors of positive circumferential resection margin after radiochemotherapy for rectal cancer: the French randomised trial ACCORD12/0405 PRODIGE 2.

Circumferential resection margin (CRM) appears as a new powerful prognostic factor of survival after surgery for rectal cancer. We aimed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial. Patients with rectal cancer were randomised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin. Mesorectal excision was performed 6 weeks after treatment. Impact of clinical, pathological and surgical variables on positive CRM (≤1 mm) were analysed by multivariate analysis. Of 565 randomised patients, CRM was recorded in 390 cases and was positive in 8% (30/390). Patients with 50 Gy plus capecitabine and oxaliplatin had a 6% rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10% rate (p=0.128). Three independent predictive factors of positive CRM were identified: abdominoperineal resection (APR) (odds ratio OR=3.24; p=0.004), vascular tumour invasion (OR=2.78; p=0.026) and poor histological response (modified Dworak 0-2) (OR=9.01; p=0.003). Significant predictive factors of positive CRM are related to type of surgery, especially APR, and poor histological prognostic factors. Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study.

Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer.

PURPOSE: The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. PATIENTS AND METHODS: Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. RESULTS: At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). CONCLUSION: At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.