Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel.

BACKGROUND: Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: To quantify the risk of small bowel adenocarcinoma and neuroendocrine tumors in patients with ulcerative colitis (UC) and Crohn's disease (CD), we undertook a population-based cohort study of all patients with IBD diagnosed in Norway and Sweden from 1987 to 2016. Patients were followed through linkage to national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) of small bowel adenocarcinomas and neuroendocrine tumors for patients with CD and UC. We excluded the first year of follow-up to reduce reverse causality. RESULTS: Among 142 008 patients with a median follow-up of 10.0 years, we identified 66 adenocarcinomas and 57 neuroendocrine tumors in the small bowel. The SIR of small bowel adenocarcinoma was 8.3 (95% CI 5.9-11.3) in CD and 2.0 (95% CI 1.2-3.1) in UC. The incidence rates of adenocarcinomas were highest in CD with stricturing disease and extent limited to the small bowel, at 14.7 (95% CI 8.2-24.2) and 15.8 (95% CI 8.4-27.0) per 100 000 person-years, respectively. The SIR of neuroendocrine tumors was 2.5 (95% CI 1.5-3.9) in CD and 2.0 (95% CI 1.4-2.8) in UC. CONCLUSIONS: Patients with CD experienced an eightfold increased risk of small bowel adenocarcinomas, patients with both UC and CD experienced an about twofold increased risk of neuroendocrine tumors, and patients with UC experienced a twofold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective.

Effectiveness of digital feedback on patient experience and 30-day complications after screening colonoscopy: a randomized health services study.

Background and study aims European guidelines (ESGE) recommend measuring patient experience and 30-day complication rate after colonoscopy. We compared digital and paper-based feedback on patients' experience and 30-day complications after screening colonoscopy. Patients and methods Screenees attending for primary screening colonoscopies in two centers from September 2015 to December 2016 were randomized (1:1) to an intervention arm (choice of feedback method) or control arm (routine paper-based feedback). Participants in the intervention arm could choose preferred feedback method (paper-based, automated telephone or online survey) and were contacted by automated telephone 30 days after colonoscopy to assess complications. Control group participants self-reported complications. Primary and secondary endpoints were response rates to feedback and complications questionnaire, respectively. Results There were 1,281 and 1,260 participants in the intervention and control arms, respectively. There was no significant difference in response rate between study groups (64.8 % vs 61.5 %; P  = 0.08). Free choice of feedback improved response for participants identified as poor responders: younger than 60 years (60.8 % vs 54.7 %; P  = 0.031), male (64.0 % vs 58.6 %; P  = 0.045) and in small non-public center (56.2 % vs 42.5 %; P  = 0.043). In the intervention arm, 1,168 participants (91.2 %) answered the phone call concerning complications. A total of 79 participants (6.2 %) reported complications, of which two (0.2 %) were verified by telephone as clinically relevant. No complications were self-reported in the control group. Conclusion The overall response rate was not significantly improved with digital feedback, yet the technology yielded significant improvement in participants defined as poor responders. Our study demonstrated feasibility and efficacy of digital patient feedback about complications after colonoscopy.

Systematic review with meta-analysis: the comparative effectiveness of aspirin vs. screening for colorectal cancer prevention.

BACKGROUND: Both aspirin use and screening with flexible sigmoidoscopy or guaiac faecal occult blood testing (FOBT) may reduce mortality from colorectal cancer, but comparative effectiveness of these interventions is unknown. AIM: To compare aspirin to guaiac FOBT screening with regard to incidence and mortality of colorectal cancer in a network meta-analysis. METHODS: We searched Medline, EMBASE and the COCHRANE central register (CENTRAL) for relevant randomised trials identified until 31 October 2015. Randomised trials in average-risk populations that reported colorectal cancer mortality, colorectal cancer incidence, or both, with a minimum follow-up of 2 years, and more than 100 randomised individuals were included. Three investigators independently extracted data. We calculated relative risks [RR with 95% predictive intervals (PrIs)] for the comparison of the interventions by frequentist network meta-analyses. RESULTS: The effect of aspirin on colorectal cancer mortality was similar to FOBT (RR 1.03; 95% PrI 0.76-1.39) and flexible sigmoidoscopy (RR 1.16; 95% PrI 0.84-1.60). Aspirin was more effective than FOBT (RR 0.36; 95% PrI 0.22-0.59) and flexible sigmoidoscopy (RR 0.37; 95% PrI 0.22-0.62) in preventing death from or cancer in the proximal colon. Aspirin was equally effective as screening in reducing colorectal cancer incidence, while flexible sigmoidoscopy was superior to FOBT (RR 0.84; 95% PrI 0.72-0.97). CONCLUSIONS: Low-dose aspirin seems to be equally effective as flexible sigmoidoscopy or guaiac FOBT screening to reduce colorectal cancer incidence and mortality, and more effective for cancers in the proximal colon. A randomised comparative effectiveness trial of aspirin vs. screening is warranted.

Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of endoscopic resection of large colorectal polyps. DESIGN: Relevant publications were identified in MEDLINE/EMBASE/Cochrane Central Register for the period 1966-2014. Studies in which ≥20 mm colorectal neoplastic lesions were treated with endoscopic resection were included. Rates of postendoscopic resection surgery due to non-curative resection or adverse events, as well as the rates of complete endoscopic removal, invasive cancer, adverse events, recurrence and mortality, were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random effect models. I2 statistic was used to describe the variation across studies due to heterogeneity. Meta-regression analysis was also performed. RESULTS: 50 studies including 6442 patients and 6779 large polyps were included in the analyses. Overall, 503 out of 6442 patients (pooled rate: 8%, 95% CI 7% to 10%, I2=78.6%) underwent surgery due to non-curative endoscopic resection, and 31/6442 (pooled rate: 1%, 95% CI 0.7% to 1.4%, I2=0%) to adverse events. Invasive cancer at histology, non-curative endoscopic resection, synchronous lesions and recurrence accounted for 58%, 28%, 2.2% and 5.9% of all the surgeries, respectively. Endoscopic perforation occurred in 96/6595 (1.5%, 95% CI 1.2% to 1.7%) polyps, while bleeding in 423/6474 (6.5%, 95% CI 5.9% to 7.1%). Overall, 5334 patients entered in surveillance, 502/5836 (8.6%, 95% CI 7.9% to 9.3%) being lost at follow-up. Endoscopic recurrence was detected in 735/5334 patients (13.8%, 95% CI 12.9% to 14.7%), being an invasive cancer in 14/5334 (0.3%, 95% CI 0.1% to 0.4%). Endoscopic treatment was successful in 664/735 cases (90.3%, 95% CI 88.2% to 92.5%). Mortality related with management of large polyps was reported in 5/6278 cases (0.08%, 95% CI 0.01% to 0.15%). CONCLUSIONS: Endoscopic resection of large polyps appeared to be an extremely effective and safe intervention. However, an adequate endoscopic surveillance is necessary for its long-term efficacy.

Comparative analysis of breast cancer mortality following mammography screening in Denmark and Norway.

BACKGROUND: Denmark and Norway are the best countries to study effects of mammography screening, because they are the only countries with stepwise introduction of nationwide mammography screening, enabling comparative effectiveness studies of high quality. Although Denmark and Norway are countries with similar populations and health care systems, reported reductions in breast cancer mortality (incidence-based) caused by screening differed vastly; 25% in Denmark versus 10% in Norway. This study explores reasons for this difference. PATIENTS AND METHODS: We compared two published studies from the Danish and Norwegian screening programs (Olsen et al., 2005; Kalager et al., 2010) investigating biennial mammography screening for women age 50-69 years. Four comparison groups of women were constructed ('current' and 'historical screening groups'; 'current' and 'historical nonscreening groups') based on county of residence. We calculated incidence-based breast cancer mortality in the current versus the historical period for screening and nonscreening groups, using mortality rate ratios (MRR) in the two countries, accounting for concomitant changes in breast cancer mortality. RESULTS: In the screening groups, similar reductions in breast cancer mortality were found when periods preceding and following start of screening were compared, in Denmark [25%; MRR 0.75; 95% confidence interval (CI) 0.64% to 0.88%] and in Norway (28%; MRR 0.72; 95% CI 0.63% to 0.81%). However, mortality increased in Denmark in the current nonscreening group compared with the historical nonscreening group; for women >59 years, breast cancer mortality increased by 14% (MRR 1.14, 95% CI 1.07-1.22), whereas in Norway a 19% reduction was seen (MRR 0.81, 95% CI 0.72-0.92). This increase accounts for the different relative effect of screening in Denmark and Norway; 25% breast cancer mortality reduction in Denmark, 10% in Norway. CONCLUSIONS: The seemingly larger effect of screening in Denmark may not be solely attributable to screening itself, but to increased breast cancer mortality in women older than 59 years not invited to screening.

Current status of screening for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. A well-defined precursor lesion (adenoma) and a long preclinical course make CRC a candidate for screening. This paper reviews the current evidence for the most important tests that are widely used or under development for population-based screening. MATERIAL AND METHODS: In this narrative review, we scrutinized all papers we have been aware of, and carried out searches in PubMed and Cochrane library for relevant literature. RESULTS: Two screening methods have been shown to reduce CRC mortality in randomised trials: repetitive faecal occult blood testing (FOBT) reduces CRC mortality by 16%; once-only flexible sigmoidoscopy (FS) by 28%. FS screening also reduces CRC incidence (by 18%), FOBT does not. Colonoscopy screening has a potentially larger effect on CRC incidence and mortality, but randomised trials are lacking. New screening methods are on the horizon but need to be tested in large clinical trials before implementation in population screening. CONCLUSIONS: FS screening reduces CRC incidence and CRC mortality by removal of adenomas; FOBT reduces CRC mortality by early detection of cancer. Several other tests are available, but none has been evaluated in randomised trials. Screening strategies differ considerably across countries.

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).

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

Principles, effectiveness and caveats in screening for cancer.

BACKGROUND: Cancer screening has the potential to prevent or reduce incidence and mortality of the target disease, but may also be harmful and have unwanted side-effects. METHODS: This review explains the basic principles of cancer screening, common pitfalls in evaluation of effectiveness and harms of screening, and summarizes the evidence for effects and harms of the most commonly used cancer screening tools. RESULTS: Cancer screening has either been established or is considered for breast, lung, prostate, cervical and colorectal cancer. In contrast, screening for gastrointestinal malignancies outside the large bowel is not generally accepted, available or implemented. Oesophageal and gastric carcinoma, and hepatocellular carcinoma, may be subject to screening in certain risk populations, but currently not for population screening based on available technology. Screening for colorectal cancer and cervical cancer by endoscopy and cytology respectively can decrease incidence of the target disease, whereas screening tools for lung, prostate and breast cancer detect early-stage invasive disease and thus do not decrease disease incidence. Overdiagnosis (detection of cancers that will not have become clinically apparent in the absence of screening) is a challenge in lung, prostate and breast cancer screening. The improvement of quality of clinical practice following the introduction of cancer screening programmes is an appreciated 'side-effect', but it is important to disentangle the effect of screening on cancer incidence and mortality from that of quality improvement of clinical services. As new, powerful screening tests emerge-particularly in molecular and genetic fields, but also in radiology and other clinical diagnostics-the basic requirements for screening evaluation and implementation must be borne in mind. CONCLUSION: Cancer screening has been established for several cancer forms in Europe. The potential for incidence and mortality reduction is good, but harms do exist that need to be addressed, and communicated to the public.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Quality assurance in endoscopy in colorectal cancer screening and diagnosis.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in endoscopy includes 50 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of endoscopy and other elements in the screening process, including multidisciplinary diagnosis and management of the disease.

The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer.

BACKGROUND AND STUDY AIM: While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. STUDY DESIGN: Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. CONCLUSIONS: The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.

Reduced pain during screening colonoscopy with an ultrathin colonoscope: a randomized controlled trial.

BACKGROUND AND STUDY AIMS: Screening colonoscopy for colorectal cancer (CRC) is recommended in several countries, but uptake rates are often low. Fear of pain and also time-consuming costly sedation are barriers for colonoscopy, and thus development of colonoscopy equipment that decreases patient discomfort is worthwhile. This randomized controlled trial investigated the performance of an ultrathin colonoscope in CRC screening. PATIENTS AND METHODS: Consecutive participants in a colonoscopy screening trial were randomized to examination with an ultrathin prototype colonoscope or a standard colonoscope. The main outcome measure was pain during the examination. Participants rated pain (no, slight, moderate, severe) using a validated questionnaire. RESULTS: From 187 enrolled participants (80 women [43 %]), 162 (87 %) responded to the questionnaire. The study groups were similar regarding baseline characteristics. Pain scores were significantly lower in the prototype instrument group compared with the standard group (78 % vs. 29 % of patients with no pain in prototype and standard groups, respectively; odds ratio [OR] 0.11; 95 % confidence interval [CI] 0.06 - 0.23; P < 0.001). Cecal intubation rate was 98 % in the prototype group and 92 % in the standard group (P = 0.085). Sedation was used in 2 % and 7 % in the prototype and standard groups respectively (P = 0.12). Adenoma detection rate was 13 % in the prototype group vs. 24 % in the standard group (P = 0.052). CONCLUSION: The new ultrathin Olympus colonoscope decreases patient pain during screening colonoscopy. This feature may improve uptake and patient satisfaction in screening colonoscopy. Further study is needed to evaluate the lower adenoma detection rate.

Withdrawal time as a quality indicator for colonoscopy - a nationwide analysis.

BACKGROUND AND STUDY AIMS: A withdrawal time of at least 6 min has been recommended as a quality indicator for colonoscopy. One drawback of many of the studies that have investigated withdrawal time and produced conflicting results has been their single-center design involving few endoscopists. Therefore, the validity of withdrawal time as a quality measure remains unclear. This study explores the value of individual withdrawal time in a nationwide analysis. PATIENTS AND METHODS: This prospective cohort study comprised data from outpatient colonoscopies performed at 19 Norwegian centers from January to September 2009 and registered in the Norwegian Gastronet Quality Assurance (QA) program. The participating endoscopists were characterized by their median withdrawal time for visual colonoscopies (diagnostic colonoscopies without biopsy or therapy) and categorized into two visual withdrawal time (VWT) groups (< 6 min or ≥ 6 min) to analyze the predictive value of VWT for detection of one or more polyps ≥ 5 mm in diameter using multiple logistic regression models. RESULTS: The study included 4429 consecutive colonoscopies performed by 67 endoscopists. The adjusted odds ratio for the detection of polyps ≥ 5 mm was 1.21 (95 %CI 0.94 - 1.56, P = 0.14) for endoscopists with a median VWT ≥ 6 min compared with endoscopists with a median VWT < 6 min. CONCLUSION: Withdrawal time using 6 min as the threshold is not a strong predictor of the likelihood of finding a polyp during colonoscopy and should not be used as a quality indicator.

Incontinence after colonoscopy--an unrecognized and preventable problem. A cross-sectional study from the Gastronet quality assurance program.

BACKGROUND: Colonoscopy requires insufflation of gas for visualization of the bowel wall. Worldwide, this is usually done using air. The aim of the present study was to assess the risk of postcolonoscopy incontinence, and to investigate whether insufflation of CO2 instead of air may reduce this risk, since it is easily absorbed through the bowel mucosa. METHODS: This is a prospective multicenter study of colonoscopy patients undergoing bowel insufflation using air or CO2. A successive series of colonoscopies were reported to a national quality assurance program in Norway between January and December 2009 from 21 endoscopy centers with varying insufflation practices. The study comprised 7812 patients aged 18 years or older who were referred for outpatient colonoscopy. Of these, 5015 underwent colonoscopy performed using air and 2797 colonoscopy using CO2 insufflation. RESULTS: Patient-reported incontinence up to 24 h after colonoscopy was compared using binary logistic regression analysis for the type of gas used for insufflation. The air and CO2 patient groups were comparable with regard to age, sex, indication for colonoscopy, and sedation practice. Incontinence was reported by 336 out of 7812 patients (4.3%). Incontinence was significantly less frequent in the CO2 group than in the air group [2.1% versus 5.5%; adjusted odds ratio (OR) 0.38; 95%CI 0.28-0.50; P < 0.001]. Female patients had a higher risk of incontinence than men (adjusted OR 1.77; 95% CI 1.39-2.24; P < 0.001). CONCLUSION: About every 20th patient undergoing colonoscopy using standard air insufflation experiences postexamination incontinence. This proportion can be reduced by 60% by converting from air insufflation to insufflation with the absorbable CO2.