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Background Women and men with colorectal adenomas are at increased risk of colorectal cancer and colonoscopic surveillance is recommended. However, the long-term cancer risk remains unknown. Aims To investigate colorectal cancer incidence and mortality after adenoma removal in women and men METHODS: We identified all individuals who had adenomas removed in Norway from 1993 to 2007, with follow-up through 2018. We calculated standardized incidence ratios (SIR) and incidence-based mortality ratios (SMR) with 95% confidence intervals (CI) for colorectal cancer in women and men using the female and male population for comparison. We defined high-risk adenomas as ≥2 adenomas, villous component, or high-grade dysplasia. Results The cohort comprised 40 293 individuals. During median follow-up of 13.0 years, 1079 women (5.5%) and 866 men (4.2%) developed colorectal cancer; 328 women (1.7%) and 275 men (1.3%) died of colorectal cancer. Colorectal cancer incidence was more increased in women (SIR 1.64, 95% CI 1.54-1.74) than in men (SIR 1.12, 95% CI 1.05-1.19). Colorectal cancer mortality was increased in women (SMR 1.13, 95% CI 1.02-1.26) and reduced in men (SMR 0.79, 95% CI 0.71-0.89). Women with high-risk adenomas had an increased risk of colorectal cancer death (SMR 1.37, 95% CI 1.19-1.57); women with low-risk adenomas (SMR 0.90, 95% CI 0.76-1.07) and men with high-risk adenomas had a similar risk (SMR 0.89, 95% CI 0.76-1.04), while men with low-risk adenomas had reduced risk (SMR 0.70, 95% CI 0.59-0.84). Conclusions After adenoma removal, women had an increased risk of colorectal cancer death, while men had reduced risk, compared to the general female and male populations. Sex-specific surveillance recommendations after adenoma removal should be considered.

Background Norway and Sweden have similar populations and health care systems, but different reactions to the COVID-19 pandemic. Norway closed educational institutions, and banned sports and cultural activities; Sweden kept most institutions and training facilities open. We aimed to compare peoples’ attitudes towards authorities and control measures, and perceived impact of the pandemic and implemented control measures on life in Norway and Sweden. Methods Anonymous web-based surveys for individuals age 15 or older distributed through Facebook using the snowball method, in Norway and Sweden from mid-March to mid-April, 2020. The survey contained questions about perceived threat of the pandemic, views on infection control measures, and impact on daily life. We performed descriptive analyses of the responses and compared the two countries. Results 3508 individuals participated in the survey (Norway 3000; Sweden 508). 79% were women, the majority were 30–49 years (Norway 60%; Sweden 47%), and about 45% of the participants in both countries had more than 4 years of higher education. Participants had high trust in the health services, but differed in the degree of trust in their government (High trust in Norway 17%; Sweden 37%). More Norwegians than Swedes agreed that school closure was a good measure (Norway 66%; Sweden 18%), that countries with open schools were irresponsible (Norway 65%; Sweden 23%), and that the threat from repercussions of the mitigation measures were large or very large (Norway 71%; Sweden 56%). Both countries had a high compliance with infection preventive measures (> 98%). Many lived a more sedentary life (Norway 69%; Sweden 50%) and ate more (Norway 44%; Sweden 33%) during the pandemic. Conclusion Sweden had more trust in the authorities, while Norwegians reported a more negative lifestyle during the pandemic. The level of trust in the health care system and self-reported compliance with preventive measures was high in both countries despite the differences in infection control measures.

Background Artificial intelligence (AI)-based polyp detection systems are used during colonoscopy with the aim of increasing lesion detection and improving colonoscopy quality. Patients and methods: We performed a systematic review and meta-analysis of prospective trials to determine the value of AI-based polyp detection systems for detection of polyps and colorectal cancer. We performed systematic searches in MEDLINE, EMBASE, and Cochrane CENTRAL. Independent reviewers screened studies and assessed eligibility, certainty of evidence, and risk of bias. We compared colonoscopy with and without AI by calculating relative and absolute risks and mean differences for detection of polyps, adenomas, and colorectal cancer. Results Five randomized trials were eligible for analysis. Colonoscopy with AI increased adenoma detection rates (ADRs) and polyp detection rates (PDRs) compared to colonoscopy without AI (values given with 95 %CI). ADR with AI was 29.6 % (22.2 % – 37.0 %) versus 19.3 % (12.7 % – 25.9 %) without AI; relative risk (RR] 1.52 (1.31 – 1.77), with high certainty. PDR was 45.4 % (41.1 % – 49.8 %) with AI versus 30.6 % (26.5 % – 34.6 %) without AI; RR 1.48 (1.37 – 1.60), with high certainty. There was no difference in detection of advanced adenomas (mean advanced adenomas per colonoscopy 0.03 for each group, high certainty). Mean adenomas detected per colonoscopy was higher for small adenomas (≤ 5 mm) for AI versus non-AI (mean difference 0.15 [0.12 – 0.18]), but not for larger adenomas (> 5 – ≤ 10 mm, mean difference 0.03 [0.01 – 0.05]; > 10 mm, mean difference 0.01 [0.00 – 0.02]; high certainty). Data on cancer are unavailable. Conclusions AI-based polyp detection systems during colonoscopy increase detection of small nonadvanced adenomas and polyps, but not of advanced adenomas.

Background Patients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk of biliary disease necessitating endoscopic retrograde cholangiopancreatography (ERCP). The most widely used approaches to perform ERCP after RYGB are laparoscopy-assisted ERCP (LA-ERCP) and balloon enteroscopy-assisted ERCP (BEA-ERCP). There are few studies comparing these procedures. We aimed to compare the performance, benefits, and harms of LA-ERCP and BEA-ERCP in RYGB patients. Methods We identified all RYGB patients who underwent ERCP at two tertiary care endoscopy centers in Oslo, Norway between May 2013 and December 2017. One center performed BEA-ERCP, the other LA-ERCP. Procedure success was defined as fulfillment of the therapeutic or diagnostic aim, according to the procedure description. Adverse events were classified according to the Clavien–Dindo grading system. Results During the study period, 40 BEA-ERCP and 39 LA-ERCP procedures were performed in 68 patients. Procedure success rate was 72.5 % for BEA-ERCP and 87.2 % for LA-ERCP (P = 0.14). Adverse events occurred in 18 % of BEA-ERCP and 28 % of LA-ERCP (P = 0.23). Serious adverse events (Clavien–Dindo grade ≥ 3b) occurred in 2.5 % of BEA-ERCP and 7.7 % of LA-ERCP procedures (P = 0.36). Concomitant cholecystectomy was performed in 25 of the 39 LA-ERCP procedures. The median procedure times for LA-ERCP performed with and without concomitant cholecystectomy were 201 minutes and 140 minutes, respectively, and for BEA-ERCP was 125 minutes. Conclusions In experienced hands, both LA-ERCP and BEA-ERCP have high success rates after RYGB. The choice of approach should be individualized according to patient characteristics and available physician competence.

During the COVID-19 pandemic, the need for rapid legal interventions to protect public health has challenged standards of evidence generation and implementation. Investigators have generated high-quality evidence for drugs and vaccines at remarkable speed, but COVID-19 mitigation measures enforced by laws and regulations remain guided by the precautionary principle rather than by empirical evidence. This article discusses new concepts for embedded evidence generation for legal public health interventions in times of crisis.

Introduction Because individuals with serrated polyps and adenomas are at increased risk of developing new polyps and colorectal cancer (CRC), surveillance after resection is justified. After adenoma resection, most international guidelines are consistent, but recommendations for surveillance after serrated polyp resection vary. The United States Multi-Society Taskforce on CRC (US-MSTF) base surveillance intervals on serrated polyp subtype (traditional serrated adenoma, sessile serrated polyp, hyperplastic polyps), while the European Society of Gastrointestinal Endoscopy (ESGE) guidelines do not take serrated polyp subtype into account. We evaluated the implications of this difference in a primary colonoscopy screening cohort. Methods We included participants from a large colonoscopy screening trial. In a post-hoc simulation, assuming full protocol adherence, we determined the surveillance interval for each subject based on their polyp burden, using the most recent US-MSTF and ESGE guidelines. Results We included 5323 participants, of whom 1228 had one or more serrated polyps. In 5201 of all participants (98 %; Cohen’s kappa 0.90) and in 1106 of those with serrated polyps (90 %; Cohen’s kappa 0.80), both guidelines recommended identical surveillance intervals. Recommendations for a 3-year surveillance interval were identical between the two guidelines. All 122 subjects with discordant recommendations would receive a follow-up colonoscopy after 10 years using ESGE guidance and after 5 years using US-MSTF guidance. Conclusion Despite the different criteria used to determine surveillance after serrated polyp resection, most individuals are recommended identical colonoscopy surveillance intervals whether following the ESGE or US-MSTF guidelines. This suggests that surveillance recommendations do not need to consider the serrated polyp subtype.

Background: Norway and Sweden are similar countries in terms of socioeconomics and health care. Norway implemented extensive COVID-19 measures, such as school closures and lockdowns, whereas Sweden did not. Aims: To compare mortality in Norway and Sweden, two similar countries with very different mitigation measures against COVID-19. Methods: Using real-world data from national registries, we compared all-cause and COVID-19-related mortality rates with 95% confidence intervals (CI) per 100,000 person-weeks and mortality rate ratios (MRR) comparing the five preceding years (2015–2019) with the pandemic year (2020) in Norway and Sweden. Results: In Norway, all-cause mortality was stable from 2015 to 2019 (mortality rate 14.6–15.1 per 100,000 person-weeks; mean mortality rate 14.9) and was lower in 2020 than from 2015 to 2019 (mortality rate 14.4; MRR 0.97; 95% CI 0.96–0.98). In Sweden, all-cause mortality was stable from 2015 to 2018 (mortality rate 17.0–17.8; mean mortality rate 17.1) and similar to that in 2020 (mortality rate 17.6), but lower in 2019 (mortality rate 16.2). Compared with the years 2015–2019, all-cause mortality in the pandemic year was 3% higher due to the lower rate in 2019 (MRR 1.03; 95% CI 1.02–1.04). Excess mortality was confined to people aged ⩾70 years in Sweden compared with previous years. The COVID-19-associated mortality rates per 100,000 person-weeks during the first wave of the pandemic were 0.3 in Norway and 2.9 in Sweden. Conclusions: All-cause mortality in 2020 decreased in Norway and increased in Sweden compared with previous years. The observed excess deaths in Sweden during the pandemic may, in part, be explained by mortality displacement due to the low all-cause mortality in the previous year.

Background: Observational studies are increasingly used to estimate the effectiveness of cancer screening. However, the validity of such studies remains uncertain. Methods: 98,678 individuals were included in the Norwegian Colorectal Cancer Prevention trial, a randomized sigmoidoscopy screening trial. We used the trial data and designed case-control studies nested among individuals randomized to sigmoidoscopy and compared the results with those from intention-to-treat and per-protocol analyses to test the validity of the case-control design to estimate screening effect on colorectal cancer incidence and mortality, and all-cause mortality. We analyzed the case-control studies with the following methodologies: The logistic regression method, where we adjusted for self-selection in multivariable regression models including age, sex, comorbidity, socioeconomics and ethnicity; and the self-selection method where we adjusted for self-selection by different unscreened groups: regional - and national reference population. The trial is registered with ClinicalTrials.gov, NCT00119912. Findings: In intention-to-treat analysis of the randomized trial, sigmoidoscopy screening reduced colorectal cancer mortality by 19% (relative risk (RR) 0.81; 95% CI 0.67-0.99). When the same data were analyzed with a case-control design, the reductions varied between 44% (RR 0.56; 95% CI 0.33-0.97) and 67% (odds ratio (OR) 0.33; 95% CI 0.22-0.51) depending on the method used. While the intention-to-treat analysis showed no screening benefit on all-cause mortality (RR 1.00; 95% CI 0.97-1.03), the case-control studies suggested a benefit between 22% (RR 0.78; 95% CI 0.71-0.85) and 57% (OR 0.42; 95% CI 0.39-0.45) depending on the method used. Interpretation: Observational studies may overestimate the benefits of cancer screening and should therefore not guide screening policies. Clinical Trials: ClinicalTrials.gov, NCT00119912 Funding: The study received intramural funding from the University of Oslo and Oslo University Hospital. No external funding was provided. Declaration of Interest: None to declare. Ethical Approval: The NORCCAP trial was approved by the Ethics Committee of South-East Norway (project ID S-98052) and the Norwegian Data Protection Authority (Project ID 98/1408). The current study was approved by the NORCCAP steering committee.

Background Closed fitness centers during the Covid-19 pandemic may negatively impact health and wellbeing. We assessed whether training at fitness centers increases the risk of SARS-CoV-2 virus infection. Methods In a two-group parallel randomized controlled trial, fitness center members aged 18 to 64 without Covid-19-relevant comorbidities, were randomized to access to training at a fitness center or no-access. Fitness centers applied physical distancing (1 m for floor exercise, 2 m for high-intensity classes) and enhanced hand and surface hygiene. Primary outcomes were SARS-CoV-2 RNA status by polymerase chain reaction (PCR) after 14 days, hospital admission after 21 days. The secondary endpoint was SARS-CoV-2 antibody status after 1 month. Results 3764 individuals were randomized; 1896 to the training arm and 1868 to the no-training arm. In the training arm, 81.8% trained at least once, and 38.5% trained ≥six times. Of 3016 individuals who returned the SARS-CoV-2 RNA tests (80.5%), there was one positive test in the training arm, and none in the no-training arm (risk difference 0.053%; 95% CI − 0.050 to 0.156%; p = 0.32). Eleven individuals in the training arm (0.8% of tested) and 27 in the no-training arm (2.4% of tested) tested positive for SARS-CoV-2 antibodies (risk difference − 0.87%; 95%CI − 1.52% to − 0.23%; p = 0.001). No outpatient visits or hospital admissions due to Covid-19 occurred in either arm. Conclusion Provided good hygiene and physical distancing measures and low population prevalence of SARS-CoV-2 infection, there was no increased infection risk of SARS-CoV-2 in fitness centers in Oslo, Norway for individuals without Covid-19-relevant comorbidities. Trial registration The trial was prospectively registered in ClinicalTrials.gov on May 13, 2020. Due to administrative issues it was first posted on the register website on May 29, 2020: NCT04406909.

Background and aims: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. Patients and methods: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. Results: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. Conclusions: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Background Whole body ischemia and reperfusion injury after cardiac arrest leads to the massive inflammation clinically manifested in the post-cardiac arrest syndrome. Previous studies on the inflammatory effect on circulatory failure after cardiac arrest have either investigated a selected patient group or a limited part of the inflammatory mechanisms. We examined the association between cardiac arrest characteristics and inflammatory biomarkers, and between inflammatory biomarkers and circulatory failure after cardiac arrest, in an unselected patient cohort. Methods This was a prospective study of 50 consecutive patients with out-of-hospital cardiac arrest. Circulation was invasively monitored from admission until day five, whereas inflammatory biomarkers, i.e. complement activation, cytokines and endothelial injury, were measured daily. We identified predictors for an increased inflammatory response, and associations between the inflammatory response and circulatory failure. Results We found a marked and broad inflammatory response in patients after cardiac arrest, which was associated with clinical outcome. Long time to return of spontaneous circulation and high lactate level at admission were associated with increased complement activation (TCC and C3bc), pro-inflammatory cytokines (IL-6, IL-8) and endothelial injury (syndecan-1) at admission. These biomarkers were in turn significantly associated with lower mean arterial blood pressure, lower cardiac output and lower systemic vascular resistance, and increased need of circulatory support in the initial phase. High levels of TCC and IL-6 at admission were significantly associated with increased 30-days mortality. Conclusion Inflammatory biomarkers, including complement activation, cytokines and endothelial injury, were associated with increased circulatory failure in the initial period after cardiac arrest.

ObjectivesNorway and Sweden are similar countries regarding ethnicity, socioeconomics and health care. To combat Covid-19, Norway implemented extensive measures such as school closures and lock-downs, while Sweden has been criticised for relaxed measures against Covid-19. We compared the effect of the different national strategies on all-cause and Covid-19 associated mortality.DesignRetrospective cohort.SettingThe countries Norway and Sweden.ParticipantsAll inhabitants.Main outcome measuresWe calculated weekly mortality rates (MR) with 95% confidence intervals (CI) per 100,000 individuals as well as mortality rate ratios (MRR) comparing the epidemic year (29th July, 2019 to 26th July, 2020) to the four preceding years (July 2015 to July 2019). We also compared Covid-19 associated deaths and mortality rates for the weeks of the epidemic in Norway and Sweden (16th March to 26th July, 2020).ResultsIn Norway, mortality rates were stable during the first three 12-month periods of 2015/16; 2016/17 and 2017/18 (MR 14.8 to 15.1 per 100,000), and slightly lower in the two most recent periods including during epidemic period (2018/19 and 2019/20; 14.5 per 100,000). In Sweden, all-cause mortality was stable during the first three 12-month periods of 2015/16; 2016/17 and 2017/18 (MR 17.2 to 17.5 per 100,000), but lower in the year 2018/19 immediately preceding the epidemic (16.2 per 100,000). Covid-19 associated mortality rates were 0.2 per 100,000 (95%CI 0.1 to 0.4) in Norway and 2.9 (95%CI 1.9 to 3.9) in Sweden. The increase in mortality was confined to individuals in 70 years or older.ConclusionsAll-cause mortality remained unaltered in Norway. In Sweden, the observed increase in all-cause mortality during Covid-19 was partly due to a lower than expected mortality preceding the epidemic and the observed excess mortality, was followed by a lower than expected mortality after the first Covid-19 wave. This may suggest mortality displacement.Strengths and limitations of this studyCompares two similar contries in all aspects but the handling of the Covid-19 epidemicEvaluates the mortality for several years before and during the epidemicProvides a possible explanation of the observed mortality changesDiscusses the socioeconomic effects of the different strategies in the two countriesDoes not evaluate cause-specific mortality

Background Endoscopic screening with polypectomy has been shown to reduce colorectal cancer incidence in randomized trials. Incomplete polyp removal and subsequent development of post-colonoscopy cancers may attenuate the effect of screening. This study aimed to quantify the extent of incomplete polyp removal. Methods We included patients aged 50–75 years with nonpedunculated polyps ≥ 5 mm removed during colonoscopy at four hospitals in Norway. To evaluate completeness of polyp removal, biopsies from the resection margins were obtained after polypectomy. Logistic regression models were fitted to identify factors explaining incomplete resection. Results 246 patients with 339 polyps underwent polypectomy between January 2015 and June 2017. A total of 12 polyps were excluded due to biopsy electrocautery damage, and 327 polyps in 246 patients (mean age 67 years [range 42–83]; 52 % male) were included in the analysis. Overall, 54 polyps (15.9 %) in 54 patients were incompletely resected. Histological diagnosis of the polyp (sessile serrated lesions vs. adenoma, odds ratio [OR] 10.9, 95 % confidence interval [CI] 3.9–30.1) and polyp location (proximal vs. distal colon, OR 2.8, 95 %CI 1.0–7.7) were independent risk factors for incomplete removal of polyps 5–19 mm. Board-certified endoscopists were not associated with lower rates of incomplete resection compared with trainees (14.0 % vs. 14.2 %), OR 1.0 (95 %CI 0.5–2.1). Conclusion Incomplete polyp resection was frequent after polypectomy in routine clinical practice. Serrated histology and proximal location were independent risk factors for incomplete resection. The performance of board-certified gastroenterologists was not superior to that of trainees.

Colonoscopy surveillance after adenoma removal is an increasing burden in many countries. Surveillance recommendations consider characteristics of removed adenomas, but not colonoscopist performance. We investigated the impact of colonoscopist performance on colorectal cancer risk after adenoma removal.We compared colorectal cancer risk after removal of high-risk adenomas, low-risk adenomas, and after negative colonoscopy for all colonoscopies performed by colonoscopists with low vs high performance quality (adenoma detection rate20% vs ≥20%) in the Polish screening program between 2000 and 2011, with follow-up until 2017. Findings were validated in the Austrian colonoscopy screening program.A total of 173,288 Polish colonoscopies were included in the study. Of 262 colonoscopists, 160 (61.1%) were low performers, and 102 (38.9%) were high performers; 11.1% of individuals had low-risk and 6.6% had high-risk adenomas removed at screening; 82.2% had no adenomas. During 10 years of follow-up, 443 colorectal cancers were diagnosed. For low-risk adenoma individuals, colorectal cancer incidence was 0.55% (95% confidence interval [CI] 0.40-0.75) with low-performing colonoscopists vs 0.22% (95% CI 0.14-0.34) with high-performing colonoscopists (hazard ratio [HR] 2.35; 95% CI 1.31-4.21; P = .004). For individuals with high-risk adenomas, colorectal cancer incidence was 1.14% (95% CI 0.87-1.48) with low-performing colonoscopists vs 0.43% (95% CI 0.27-0.69) with high-performing colonoscopists (HR 2.69; 95% CI 1.62-4.47; P.001). After negative colonoscopy, colorectal cancer incidence was 0.30% (95% CI 0.27-0.34) for individuals examined by low-performing colonoscopists, vs 0.15% (95% CI 0.11-0.20) for high-performing (HR 2.10; 95% CI 1.52-2.91; P.001). The observed trends were reproduced in the Austrian validation cohort.Our results suggest that endoscopist performance may be an important contributor in addition to polyp characteristics in determining colorectal cancer risk after colonoscopy screening.

Background There is concern but no solid evidence that morcellation during laparoscopic or vaginal hysterectomy may cause abdominal spread and thereby impaired prognosis of incidental uterine sarcomas. Objective Our purpose was to compare survival among patients with uterine sarcomas who underwent hysterectomy with or without morcellation to test the hypothesis that morcellation impairs prognosis. Study design We identified all women in Norway diagnosed with uterine sarcoma between 1953 and 2012 through national registries and retrieved data on surgical technique and morcellation by evaluation of patient files. Patients were categorised into abdominal, laparoscopic or vaginal hysterectomy with or without morcellation. Vaginal and laparoscopic hysterectomies were introduced in 1991; our main comparison is from 1991 to 2012. We compared age-adjusted disease-specific survival of sarcoma patients treated with or without morcellation and calculated age-adjusted hazard ratios (HRs) and subdistribution HR (accounting for competing risk) with 95% confidence intervals (CIs). Results Among 1367 patients with uterine sarcoma between 1953 and 2012 in Norway, 653 were diagnosed after 1991, and 23 of these patients (3.5%) underwent morcellation. Uterine sarcoma prevalence was 3.6 per 1000 laparoscopic hysterectomies. Mean follow-up was 6.0 years in the morcellated group and 6.9 years in the non-morcellated group. The risk of dying from uterine sarcoma after morcellation was 1.5 per 1000 procedures. Sarcoma mortality was higher in the morcellated group than in the non-morcellated group (age-adjusted HR 1.90, CI 1.05–3.44; multivariate HR, 2.50, 95% CI 0.57–10.9). Age-adjusted 10-year uterine sarcoma survival was 32.2% for women treated with morcellation compared with 57.2% for non-morcellated group (difference 25.5%; CI −55.7 to 18.1). All-cause 10-year survival was 32.2% in the morcellated group and 44.1% in the non-morcellated group (difference 11.9%; CI −40.9 to 32.7). Conclusion Our results strengthen the evidence that morcellation during hysterectomy in patients with incidental uterine sarcoma may cause impaired survival. These results can guide shared decision-making in clinical practice.

Background and study aims Incomplete polyp removal has been estimated to cause 27 % of all colorectal cancers detected soon after colonoscopy. There is limited information regarding polypectomy techniques among endoscopists. The article is a nationwide survey of polypectomy techniques among Norwegian endoscopists. Materials and methods We invited all board-certified gastroenterologists in Norway to complete a web-based questionnaire about their polypectomy technique. Inadequate polypectomy techniques were defined as using biopsy forceps for polyps larger than 3 mm in diameter, using hot biopsy forceps for polypectomy, and using the same electrocautery output irrespective of polyp size and morphology. Results Twenty-six of 30 Norwegian gastroenterology departments participated in the study. A total of 119 endoscopists received the survey, and 70 (59 %) responded. Mean duration of endoscopy practice was 11.5 years, and 95 % had performed more than 1,000 colonoscopies during their career. Twenty-eight endoscopists (40 %) used one or more inadequate polypectomy techniques: 10 (14.3 %) used biopsy forceps for removal of polyps larger than 3 mm in diameter, five (7.1 %) used hot biopsy for polypectomy, and 17 (24 %) used the same electrocautery output for all polypectomies. Five (7 %) endoscopists reported that they did not remove polyps smaller than 4 mm. Conclusion A substantial number of Norwegian endoscopists use inadequate polypectomy techniques. Improved training and certification of endoscopists is warranted.

Background: The risk of hepatobiliary and pancreatic cancer in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC) has not been reliably quantified in large, prospective studies with long-term follow-up. Methods: We performed a population cohort study of all patients diagnosed with IBD in Norway and Sweden from 1987 to 2015. Participants were followed through linkage to national cancer, cause of death and population registers. We calculated standardized incidence ratios (SIR) with 95% confidence intervals (CIs) and absolute risk of hepatobiliary and pancreatic cancer by PSC status and other clinical characteristics. Results: We identified 141,960 IBD patients, 4,548 (3.2%) of these with concomitant PSC. During a median follow-up time of 10.0 years, we identified 479 biliary tract cancers (SIR 5.2, 95% CI 4.7-5.7), 127 hepatocellular carcinomas (SIR 2.1, 95% CI 1.8-2.5) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2-1.5). The relative risks were considerably higher in patients with PSC, with SIRs of 142 (95% CI 125-160) for biliary tract, 27.7 (95% CI 19.4-38.5) for hepatocellular, and 9.0 (95% CI 6.3-12.6) for pancreatic cancer. For IBD patients without PSC, we found SIRs of 2.5 (95% CI 2.2-2.9), 1.5 (1.2-1.8), and 1.2 (1.1-1.4) for biliary tract cancer, hepatocellular carcinoma, and pancreatic cancer, respectively. Conclusion: Patients with IBD experience a substantially increased risk of biliary tract cancer. Although the risk is largely confined to patients with concomitant PSC, non-PSC patients also confer a moderate excess risk. Citation Format: Jingru Yu, Erle Refsum, Lise M. Helsingen, Trine Folseraas, Alexander Ploner, Paulina Wieszczy, Ishita Barua, Henriette C. Jodal, Espen Melum, Magnus Løberg, Johannes Blom, Michael Bretthauer, Hans-Olov Adami, Mette Kalager, Weimin Ye. Risk of hepatobiliary & pancreatic cancer in inflammatory bowel disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 841.

Improved understanding of the subsequent risk death from colorectal cancer (CRC) among individuals who had adenomas removed is needed. We aimed to quantify this risk using prospectively collected data from population-based cohorts.Using Norwegian and Swedish registries, a cohort of 90,864 individuals with colorectal adenomas removed between 1980 and 2013 was identified. Surveillance was only recommended for high-risk adenomas. The validity of the registry data did not allow classification into low- and high-risk adenomas. Virtually complete follow-up was achieved through linkage to nationwide registers. We calculated incidence-based standardised mortality ratios (SMRs) with 95% confidence intervals (CI).The median follow-up was 7.2 years; 48,058 individuals were followed for more than 10 years. We observed 819 deaths (0.9%) from CRC and expected 731 CRC deaths (0.8%), corresponding to an absolute excess risk of 88 cases (0.1%) and a relative risk of 12% (SMR 1.12; 95%CI 1.05-1.20). The relative risk of CRC death following adenoma removal was slightly higher in Sweden (SMR 1.22; 95%CI 1.11-1.34) than in Norway (SMR 1.03; 95%CI 0.93-1.14), and higher in women (SMR 1.24; 95%CI 1.12-1.36) than in men (SMR 1.02; 95%CI 0.93-1.13). Among individuals with more than 10 years of follow-up, the estimates were similar to the overall cohort, absolute excess risk 0.1% (SMR 1.15; 95%CI 1.06-1.24).The excess risk of CRC death following adenoma removal is small. Optimal surveillance recommendations should be tested in randomised trials.

The view, that rapidly growing tumours are more likely than slow-growing tumours to metastasize and become lethal, has remained almost axiomatic for decades. Unaware of any solid evidence supporting this view, we undertook an exhaustive system-level analysis of intra- and intercellular signalling networks. This analysis indicated that rapid growth and metastasis are often different outcomes of complex integrated molecular events. Evidence from humans can be derived chiefly from screening interventions because interval cancers that surface clinically shortly after a negative screening test are, on average, more rapidly growing than cancers not detected by screening. We reviewed all available data limited to cancers of the breast, cervix and large bowel. The evidence from humans provides no support for the theory that rapidly growing cancers are more prone to metastasize. These findings indicate that the prevailing view should be reconsidered, as should the impact of length-biased sampling in cancer screening, and the findings provide no support for treating interval cancers more aggressively than non-interval cancers.

Background & Aims Recommendation of surveillance colonoscopy should be based on risk of colorectal cancer and death after adenoma removal. We aimed to develop a risk classification system based on colorectal cancer incidence and mortality following adenoma removal. Methods We performed a multicenter population-based cohort study of 236,089 individuals (median patient age, 56 years; 37.8% male) undergoing screening colonoscopies with adequate bowel cleansing and cecum intubation at 132 centers in the Polish National Colorectal Cancer Screening Program, from 2000 through 2011. Subjects were followed for a median 7.1 years and information was collected on colorectal cancer development and death. We used recursive partitioning and multivariable Cox models to identify associations between colorectal cancer risk and patient and adenoma characteristics (diameter, growth pattern, grade of dysplasia, and number of adenomas). We developed a risk classification system based on standardized incidence ratios, using data from the Polish population for comparison. The primary endpoints were colorectal cancer incidence and colorectal cancer death. Results We identified 130 colorectal cancers in individuals who had adenomas removed at screening (46.5 per 100,000 person-years) vs 309 in individuals without adenomas (22.2 per 100,000 person-years). Compared with individuals without adenomas, adenomas ≥20 mm in diameter and high-grade dysplasia were associated with increased risk of colorectal cancer (adjusted hazard ratios 9.25; 95% confidence interval [CI] 6.39–13.39, and 3.58; 95% CI 1.96–6.54, respectively). Compared with the general population, colorectal cancer risk was higher or comparable only for individuals with adenomas ≥20 mm in diameter (standardized incidence ratio [SIR] 2.07; 95% CI 1.40–2.93) or with high-grade dysplasia (SIR 0.79; 95% CI 0.39–1.41), whereas for individuals with other adenoma characteristics the risk was lower (SIR 0.35; 95% CI 0.28–0.44). We developed a high-risk classification based on adenoma size ≥20 mm or high-grade dysplasia (instead of the current high-risk classification cutoff of ≥3 adenomas or any adenoma with villous growth pattern, high-grade dysplasia, or ≥10 mm in diameter). Our classification system would reduce the number of individuals classified as high-risk and requiring intensive surveillance from 15,242 (36.5%) to 3980 (9.5%), without increasing risk of colorectal cancer in patients with adenomas (risk difference per 100,000 person-years, 5.6; 95% CI –10.7 to 22.0). Conclusions Using data from the Polish National Colorectal Cancer Screening Program, we developed a risk classification system that would reduce the number of individuals classified as high risk and require intensive surveillance more than 3-fold, without increasing risk of colorectal cancer in patients with adenomas. This system could optimize the use of surveillance colonoscopy.

Colorectal cancer (CRC) screening programs are far from perfect. Many crucial questions remain, yet expensive CRC screening services are implemented throughout the world without a plan on how to evaluate and improve the service. The time is ripe for improving the design of CRC screening programs.

ObjectiveTo estimate overdiagnosis of colorectal cancer (CRC) for screening with sigmoidoscopy and faecal occult blood testing (FOBT).DesignSimulation study using data from randomised trials.SettingPrimary screening, UK, NorwayParticipants152 850 individuals from the Nottingham trial and 98 678 individuals from the Norwegian Colorectal Cancer Prevention (NORCCAP) trial.InterventionCRC screening.Outcome measureWe estimated overdiagnosis using long-term data from two randomised trials: the Nottingham trial comparing FOBT screening every other year to no-screening, and the NORCCAP trial comparing once-only sigmoidoscopy screening to no-screening. To estimate the natural growth of adenomas to CRC, we used the following microsimulation models: (i) the Microsimulation Screening Analysis; (ii) the CRC Simulated Population model for Incidence and Natural history; (iii) the Simulation Model of Colorectal Cancer; (iv) a model derived by the German Cancer Research Center. We defined overdiagnosed cancers as the difference between the observed number of CRCs in the no-screening arm and the expected number of cancers in screening arm (sum of observed and prevented by adenoma removal). The amount of overdiagnosis is defined as the number of overdiagnosed cancers over the number of cancers observed in the no-screening arm.ResultsOverdiagnosis estimates were highly dependent on model assumptions. For FOBT screening with 2354 cancers observed in control arm, four out of five models predicted overdiagnosis, range 2.0% (2400 cancers expected in screening) to 7.6% (2533 cancers expected in screening). For sigmoidoscopy screening with 452 cancers observed in control arm, all models predicted overdiagnosis, range 25.2% (566 cancers expected in screening) to 128.1% (1031 cancers expected in screening).ConclusionsThe amount of overdiagnosis estimated based on the microsimulation models varied substantially. Microsimulation models may not give reliable estimates of the preventive effect of adenoma removal, and should be used with caution to inform guidelines.

SummaryBackground 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.

There is considerable variation in the quality of colonoscopy performance. The Norwegian quality assurance programme Gastronet registers outpatient colonoscopies performed in Norwegian endoscopy centres. The aim of Gastronet is long-term improvement of endoscopist and centre performance by annual feedback of performance data.The objective of this article is to perform an analysis of trends of quality indicators for colonoscopy in Gastronet.This prospective cohort study included 73,522 outpatient colonoscopies from 73 endoscopists at 25 endoscopy centres from 2003 to 2012. We used multivariate logistic regression with adjustment for relevant variables to determine annual trends of three performance indicators: caecum intubation rate, pain during the procedure, and detection rate of polyps ≥5 mm.The proportion of severely painful colonoscopies decreased from 14.8% to 9.2% (relative risk reduction of 38%; OR = 0.92 per year in Gastronet; 95% CI 0.86-1.00; p = 0.045). Caecal intubation (OR = 0.99; 95% CI 0.94-1.04; p = 0.6) and polyp detection (OR = 1.03; 95% CI 0.99-1.07; p = 0.15) remained unchanged during the study period.Pain at colonoscopy showed a significant decrease during years of Gastronet participation while caecal intubation and polyp detection remained unchanged - independent of the use of sedation and/or analgesics and level of endoscopist experience. This may be due to the Gastronet audit, but effects of improved endoscopy technology cannot be excluded.

BACKGROUND Questionnaire surveys are important for surveying the health and disease behaviour of the population, but recent years have seen a fall in participation. Our study tested whether incentives can increase participation in these surveys.MATERIAL AND METHOD We sent a questionnaire on risk factors for colorectal cancer (height, weight, smoking, self-reported diagnoses, family medical history) to non-screened participants in a randomised colonoscopy screening study for colorectal cancer: participants who were invited but did not attend for colonoscopy examination (screening-invited) and persons who were not offered colonoscopy (control group). The persons were randomised to three groups: no financial incentive, lottery scratch cards included with the form, or a prize draw for a tablet computer when they responded to the form. We followed up all the incentive groups with telephone reminder calls, and before the prize draw for the tablet computer.RESULTS Altogether 3 705 of 6 795 persons (54.5 %) responded to the questionnaire; 43.5 % of those invited for screening and 65.6 % of the control group (p < 0.001). The proportion that answered was not influenced by incentives, either among those invited for screening (42.4 % in the non-prize group, 45.5 % in the lottery scratch card group and 42.6 % in the prize draw group; p = 0.24), or in the control group (65.6 % in the non-prize group, 66.4 % in the lottery scratch card group and 64.7 % in the prize draw group; p = 0.69). Prior to reminder calls, 39.2 % responded. A further 15.3 % responded following telephone reminder calls (14.1 % of the screening-invited and 16.5 % of the control group; p < 0.001).INTERPRETATION Incentives did not increase participation in this medical questionnaire survey. Use of telephone reminder calls and telephone interviews increased participation, but whether this is more effective than other methods requires further study.

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 = 10mm 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 >= 10mm in diameter at any location, or serrated polyps >= 5mm 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.

The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear.To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men.Randomized controlled trial. (ClinicalTrials.gov: NCT00119912).Oslo and Telemark County, Norway.Adults aged 50 to 64 years at baseline without prior CRC.Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy.Age-adjusted CRC incidence and mortality stratified by sex.Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, -0.19 percentage point [95% CI, -0.49 to 0.11 percentage point]; HR, 0.92 [CI, 0.79 to 1.07]). In men, the corresponding risks were 1.72% and 2.50%, respectively (risk difference, -0.78 percentage point [CI, -1.08 to -0.48 percentage points]; hazard ratio [HR], 0.66 [CI, 0.57 to 0.78]) (P for heterogeneity = 0.004). The absolute risks for death from CRC in women were 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, -0.16 to 0.18 percentage point]; HR, 1.01 [CI, 0.77 to 1.33]). The corresponding risks for death from CRC in men were 0.49% and 0.81%, respectively (risk difference, -0.33 percentage point [CI, -0.49 to -0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014).Follow-up through national registries.Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women.Norwegian government and Norwegian Cancer Society.

Background & Aims Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). Methods We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. Results The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56–110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44–174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14–135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28–52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36–93) assuming heterogeneity (P for heterogeneity = .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344–833) years assuming heterogeneity (P for heterogeneity = .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9–22) and 122 (95% CI, 90–190) years, respectively. Conclusions We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.

Background Colonoscopy performance varies between endoscopists, but little is known about the impact of endoscopy assistants on key performance indicators. We used a large prospective colonoscopy quality database to perform an exploratory study to evaluate differences in selected quality indicators between endoscopy assistants. Methods All colonoscopies reported to the Norwegian colonoscopy quality assurance register Gastronet can be used to trace individual endoscopy assistants. We analyzed key quality indicators (cecum intubation rate, polyp detection rate, colonoscopies rated as severely painful, colonoscopies with sedation or analgesia, and satisfaction with information) for colonoscopies performed between 1 January 2013 and 31 December 2014. Differences between individual assistants were analyzed by fitting multivariable logistic regression models, with the best performing assistant at each participating hospital as reference. All models were adjusted for the endoscopist. Results 63 endoscopy assistants from 12 hospitals assisted in 15 365 colonoscopies. Compared with their top performing peers from the same hospital, one assistant was associated with cecum intubation failure, four with poor polyp detection, nine with painful colonoscopy, 16 with administration of sedation or analgesics during colonoscopy, and three with patient dissatisfaction about information given relating to the colonoscopy. The number of procedures during the study period or lifetime experience as an endoscopy assistant were not associated with any quality indicator. Conclusion In this exploratory study, there was little variation on important colonoscopy quality indicators between endoscopy assistants. However, there were differences among assistants that may be clinically important. Endoscopy assistants should be subject to quality surveillance similarly to endoscopists.

Objective To compare the effectiveness of flexible sigmoidoscopy in screening for colorectal cancer by patient sex and age. Design Pooled analysis of randomised trials (the US Prostate, Lung, Colorectal and Ovarian cancer screening trial (PLCO), the Italian Screening for Colon and Rectum trial (SCORE), and the Norwegian Colorectal Cancer Prevention trial (NORCCAP)). Data sources Aggregated data were pooled from each randomised trial on incidence of colorectal cancer and mortality stratified by sex, age at screening, and colon subsite (distal v proximal). Eligibility criteria for selecting studies Invited individuals aged 55-74 (PLCO), 55-64 (SCORE), and 50-64 (NORCCAP). Individuals were randomised to receive flexible sigmoidoscopy screening once only (SCORE and NORCCAP) or twice (PLCO), or receive usual care (no intervention). Results 287 928 individuals were included in the pooled analysis; 115 139 randomised to screening and 172 789 to usual care. Compliance rates were 58%, 63%, and 87% in SCORE, NORCCAP, and PLCO, respectively. Median follow-up was 10.5 to 12.1 years. Screening reduced the incidence of colorectal cancer in men (relative risk 0.76; 95% confidence interval 0.70 to 0.83) and women (0.83; 0.75 to 0.92). No difference in the effect of screening was seen between men younger than 60 and those older than 60. Screening reduced the incidence of colorectal cancer in women younger than 60 (relative risk 0.71; 95% confidence interval 0.59 to 0.84), but not significantly in those aged 60 or older (0.90; 0.80 to 1.02). Colorectal cancer mortality was significantly reduced in both younger and older men, and in women younger than 60. Screening reduced colorectal cancer incidence to a similar extent in the distal colon in men and women, but there was no effect of screening in the proximal colon in older women with a significant interaction between sex and age group (P=0.04). Conclusion Flexible sigmoidoscopy is an effective tool for colorectal cancer screening in men and younger women. The benefit is smaller and not statistically significant for women aged over 60; alternative screening methods that more effectively detect proximal tumours should be considered for these women.

Objective There is uncertainty whether cancer screening affects participant incentives for favourable lifestyle. The present study investigates long-term effects of colorectal cancer (CRC) screening on lifestyle changes. Design In 1999–2001, men and women drawn from the population registry were randomised to screening for CRC by flexible sigmoidoscopy (‘invited-to-screening’ arm) or to no-screening (control arm) in the Norwegian Colorectal Cancer Prevention trial. A subgroup of 3043 individuals in the ‘invited-to-screening’ and 2819 in the control arm, aged 50–55 years, randomised during 2001 had their lifestyle assessed by a questionnaire at inclusion and after 11 years (42% of cohort). The outcome was 11-year changes in lifestyle factors (body weight, smoking status, physical exercise, selected dietary habits) and in total lifestyle score (0–4 points, translating to the number of lifestyle recommendations adhered to). We compared outcomes in the two randomisation arms and attendees with positive versus negative findings. Results Total lifestyle scores improved in both arms. The improvement was smaller in the ‘invited-to-screening’ arm (score 1.43 at inclusion; 1.58 after 11 years) compared with the control arm (score 1.49 at inclusion; 1.67 after 11 years); adjusted difference −0.05 (95% CI −0.09 to −0.01; p=0.03). The change in the score was less favourable in screening attendees with a positive compared with negative screening result; adjusted difference −0.16 (95% CI −0.25 to −0.08; p Conclusions The present study suggests that possible unfavourable lifestyle changes after CRC screening are modest. Lifestyle counselling may be considered as part of cancer screening programmes. Trial registration number NCT00119912.

Fecal Microbiota for Clostridium difficile Clostridium difficile is the leading cause of nosocomial infectious diarrhea. New treatment strategies are needed. In this letter, preliminary data on fecal therapy as primary treatment are assessed.

Background & Aims Endoscopic screening for colorectal cancer (CRC) is performed at longer time intervals than the fecal occult blood test or screenings for breast or prostate cancer. This causes concerns about interval cancers, which have been proposed to progress more rapidly. We compared outcomes of patients with interval CRCs after sigmoidoscopy screening vs outcomes of patients with CRC who had not been screened. Methods We performed a secondary analysis of a randomized sigmoidoscopy screening trial in Norway with 98,684 participants (age range, 50–64 years) who were randomly assigned to groups that were (n = 20,552) or were not (n = 78,126) invited for sigmoidoscopy screening from 1999 through 2001; participants were followed up for a median 14.8 years. We compared CRC mortality and all-cause mortality between individuals who underwent screening and were diagnosed with CRC 30 days or longer after screening (interval cancer group, n = 163) and individuals diagnosed with CRC in the nonscreened group (controls, n = 1740). All CRCs in the control group were identified when they developed symptoms (clinically detected CRCs). Analyses were stratified by cancer site. We used Cox regression to estimate hazard ratio (HRs), adjusted for age and sex. Results Over the follow-up period, 43 individuals in the interval cancer group died from CRC; among controls, 525 died from CRC. CRC mortality (adjusted HR, 0.98; 95% confidence interval, 0.72–1.35; P = .92), rectosigmoid cancer mortality (adjusted HR, 1.10; 95% confidence interval, 0.63–1.92; P = .74), and all-cause mortality (adjusted HR, 0.99; 95% confidence interval, 0.76–1.27; P = .91) did not differ significantly between the interval cancer group and controls. Conclusions In this randomized sigmoidoscopy screening trial, mortality did not differ significantly between individuals with interval CRCs and unscreened patients with clinically detected CRCs. ClinicalTrials.gov identifier: NCT00119912 .

Surveillance is recommended for various GI cancers, and substantial resources are invested. However, little is known about the effect of surveillance, neither for good, nor for bad. Most evidence stems from observational studies, but observational studies of surveillance can be subject to various biases that may severely influence the results. In this chapter we discuss challenges related to various research questions, study designs, choice of endpoints, and how to deal with different forms of bias. We hope this chapter will be helpful for researchers when performing high-quality studies of surveillance, and to enable physicians and policy-makers to understand the possibilities and limitations of current evidence.

Colonoscopes with gradual stiffness have recently been developed to enhance cecal intubation.We aimed to determine if the performance of gradual stiffness colonoscopes is noninferior to that of magnetic endoscopic imaging (MEI)-guided variable stiffness colonoscopes.Consecutive patients were randomized to screening colonoscopy with Fujifilm gradual stiffness or Olympus MEI-guided variable stiffness colonoscopes. The primary endpoint was cecal intubation rate (noninferiority limit 5%). Secondary endpoints included cecal intubation time. We estimated absolute risk differences with 95% confidence intervals (CIs).We enrolled 475 patients: 222 randomized to the gradual stiffness instrument, and 253 to the MEI-guided variable stiffness instrument. Cecal intubation rate was 91.7% in the gradual stiffness group versus 95.6% in the variable stiffness group. The adjusted absolute risk for cecal intubation failure was 4.3% higher in the gradual stiffness group than in the variable stiffness group (upper CI border 8.1%). Median cecal intubation time was 13 minutes in the gradual stiffness group and 10 minutes in the variable stiffness group (The study is inconclusive with regard to noninferiority because the 95% CI for the difference in cecal intubation rate between the groups crosses the noninferiority margin. (ClinicalTrials.gov identifier: NCT01895504).

Background and study aims: Colonoscopy is frequently performed with opioid analgesia, but the impact of drug delivery timing has not been studied in detail. Low-dose opioids administered before the procedure may provide better pain control than on-demand administration when the patient experiences pain. Patients and methods: A total of 119 outpatients were randomized to receive 50 μg of fentanyl either before colonoscopy (routine group) or on demand if needed during the colonoscopy (on-demand group). Additional fentanyl or midazolam was allowed in both groups if required. The primary outcome was pain measured on both a 100-mm visual analog scale (VAS; 0 = no pain, 100 = worst possible pain) and a four-point Likert scale (no, slight, moderate, or severe pain) immediately after the procedure. Results: A total of 61 patients in the routine group and 58 patients in the on-demand group were included in the study. Mean VAS pain scores were 27.4 mm in the routine group and 30.5 mm in the on-demand group (mean difference – 3.2 mm; 95 % confidence interval – 11.9 to 5.5; P = 0.5). On the Likert scale, moderate or severe pain was experienced by 25.0 % and 31.5 % of patients in the routine and on-demand groups, respectively (p = 0.5). Cecal intubation rate and time to reach the cecum were similar between the groups. More patients in the on-demand group (81.0 %) than in the routine group (62.3 %) were able to leave the clinic without the need for recovery time (P = 0.03). Conclusion: Routine administration of fentanyl did not provide better analgesia during colonoscopy than on-demand fentanyl, and more patients needed time for recovery. Trial registration: ClinicalTrials.gov (NCT01786434).

In randomized trials, the most commonly reported method of effect estimation is intention-to-treat (ITT), and to a lesser extent the per-protocol. The ITT is preferred because it is an unbiased estimator of the effect of treatment assignment. However, if there is any non-adherence the ITT is a biased estimate of the treatment effect, defined as the contrast between the potential outcome if treated versus the potential outcome if not treated. The treatment effect is most relevant to patients. Principal stratification is a framework for estimating treatment effects that combines potential outcomes and latent adherence strata. It yields an unbiased estimator of the complier average causal effect (CACE) for a difference in means or proportions, in the setting of all-or-nothing adherence. This paper addresses estimation of the causal hazard ratio for the compliers in a setting of right censoring of a time-to-event. We propose a novel approach to operationalizing principal stratification using weights. We report the results of simulations that vary the amount of adherence and selection bias that show the hazard ratio estimators we propose have minimal bias compared to the ITT, and per-protocol estimators. We demonstrate the approach using a population based randomized controlled trial of colorectal cancer screening subject to a high frequency of nonadherence in the screening arm.

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 94959 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.