Geir Svein Hoff

• Hysing, Jan; Thalamus, Jacob; Gibbs, Charlotte Christine; Holla, Øystein Lunde; Jaioun, Keson & Hoff, Geir Svein [Show all 7 contributors for this article] (2026). Beta-Blocker Use in Acquired Long QT Syndrome is Associated with Better Survival. Journal of Pharmacy and Pharmacology Research. 10(3), p. 78–86. doi: 10.26502/fjppr.0129. Full text in Research Archive Show summary

  Objectives: To assess whether beta-blocker therapy is associated with improved prognosis in a defined cohort of patients with acquired long QT on ECG (aLQT). Methods: We included patients with prolonged QT at Telemark Hospital, Norway, 2004-2014 with at least one ECG record of QTc > 500 ms. Genetic testing was performed to exclude congenital long QT syndrome (cLQTS). Statistical analyses were performed relating survival to clinical diagnosis, biochemical parameters and pharmacological data from the hospital medical records. Stepwise Cox regression was performed to identify predictors for survival. Primary aim: To assess short (30 days) and long term (12 months) survival rate for patients with aLQT recruited from a hospital-wide ECG database stratified by beta blocker medication. Results: We included ECGs from 1531 patients. Based on genetic testing, 33 patients with cLQTS were excluded, rendering 1498 individuals with acquired long QT (aLQT) for analysis. Mean age was 70.9 years, 59% were female. 47% were on beta blocking treatment at the time of ECG documenting prolonged QT. Patients on beta-blocker were older, and had more frequently heart failure, stroke, diabetes and coronary heart disease than patients who were not on beta-blockers. Short term survival rate (30 days) for patients on beta-blocker medication was 96%, compared to 81% without beta-blocker (p<0.001). Similarly, 12-month survival rate was 80% for patients on beta-blocker compared to 68% without beta-blocker (p<0.001). Conclusions: In this observational study, beta-blocker treatment was associated with a 10-15% better survival in patients with aLQT, both short-term (30-day) and long-term (12-month) follow up.

• Birkeland, Einar Elvbakken; Kværner, Ane Sørlie; Avershina, Ekaterina; Johannessen, Cecilie Bucher -; Bemanian, Vahid & Blix, Hege Salvesen [Show all 14 contributors for this article] (2026). Microbiome signatures for detection of colorectal lesions in population-based FIT screening. Nature Communications. 17. doi: 10.1038/s41467-026-75962-1. Full text in Research Archive Show summary

  The gut microbiome has been linked to colorectal cancer (CRC) development, with microbe-based classifiers distinguishing between CRC patients and healthy controls. However, there is a lack of studies addressing the utility of the microbiome in screening-relevant settings, including both precancers and CRC. In this Norwegian population-based study, we used fecal immunochemical test (FIT) leftovers from 1034 FIT-positive (i.e. positive for occult blood) screening participants for gut metagenome profiling using shotgun sequencing. Using comprehensive clinical, demographic, and lifestyle data, we modeled gut microbiome associations with CRC screening outcomes. Combining microbial profiles with quantitative FIT values improved detection of premalignant lesions beyond optimizing the FIT value alone, even after incorporating established CRC risk factors. Still, the FIT value maintained superior discriminative ability for CRC. We confirmed enrichment of bacteria such as Fusobacterium nucleatum and Peptostreptococcus stomatis in CRC. In contrast, other bacteria previously associated with the presence of CRC, including Hungatella hathewayi and Clostridium symbiosum, as well as pks-negative Escherichia coli, were enriched in those with no neoplastic findings, suggesting that in a FIT-positive population their presence may reflect other conditions causing intestinal bleeding rather than underlying neoplasia. Microbial profiles were predominantly associated with distal rather than proximal lesions. Together, our findings highlight the potential for microbial markers to improve FIT-based CRC screening, especially by differentiating those with premalignant lesions from those who test FIT-positive for other reasons.

• Omdal, Roald; Grimstad, Tore Bjørn; Jonsson, Grete; Kvaløy, Jan Terje; Gibbs, Charlotte Christine & Reitsma, Laurens Cornelus [Show all 8 contributors for this article] (2026). Interleukin−1 receptor antagonist and heat shock protein 90alfa are independently associated with fatigue and general health in euthyroid Hashimoto’s thyroiditis. Frontiers in Endocrinology. 17. doi: 10.3389/fendo.2026.1862441. Full text in Research Archive Show summary

  Background Patients with Hashimoto’s thyroiditis frequently experience fatigue and impaired health-related quality of life (HRQOL) despite biochemical euthyroidism, suggesting that immune-mediated mechanisms beyond thyroid hormone deficiency contribute to symptom generation. The role of specific inflammatory mediators - including interleukin-1 receptor antagonist (IL-1Ra), heat shock protein 90α (HSP90α), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and anti-TPO antibodies - in relation to patient-reported outcomes (PROMs) has not been systematically examined. Methods In a cross-sectional study of 36 euthyroid patients with confirmed Hashimoto’s thyroiditis, serum/plasma levels of IL-1Ra, HSP90α, IL-6, and TNF-α were measured alongside anti-TPO. PROMs included the SF-36 General Health subscale (inverted; iGH), the Fatigue Visual Analog Scale (fVAS), and the Fatigue Severity Scale (FSS). Spearman correlations, univariable and multivariable linear regression, and principal component analysis (PCA) were applied. Results The cohort displayed severe fatigue at baseline (median fVAS 85, FSS 6.7, SF-36 GH 16). IL-1Ra was the most consistent biomarker correlate of symptom burden, independently associated with poorer general health and more fatigue across all regression models. HSP90α showed an inverse and independent association with fatigue in multivariable models, suggesting a potentially protective role. IL-6 contributed in correlation analysis only, while TNF-α and anti-TPO were not significantly associated with any PROM in any analytical approach. Conclusion IL-1Ra and HSP90α, but not anti-TPO, are independently associated with fatigue and general health in euthyroid Hashimoto’s thyroiditis, pointing to IL-1 pathway activity as associated with symptom burden and potentially playing a key role in this condition.

• Botteri, Edoardo; Holme, Øyvind; Løberg, Magnus; Bretthauer, Michael; Kalager, Mette & Randel, Kristin Ranheim [Show all 7 contributors for this article] (2026). Twenty-Three–Year Benefits of Sigmoidoscopy Screening for Colorectal Cancer A Randomized Trial. Annals of Internal Medicine. ISSN 0003-4819. 179(6), p. 804–811. doi: 10.7326/annals-25-05456. Full text in Research Archive Show summary

  Background: Meta-analyses of randomized trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and death for 15 years. Objective: To report the benefits of sigmoidoscopy after 23 years. Design: Randomized controlled trial. (NORCCAP [Norwegian Colorectal Cancer Prevention], ClinicalTrials.gov: NCT00119912) Setting: Population of Oslo and Telemark County, Norway. Participants: Persons aged 50 to 64 years without CRC at randomization. Intervention: Screening with once-only sigmoidoscopy, with or without 1 fecal immunochemical test, or no screening. Measurements: Colorectal cancer incidence and death. Results: A total of 100 210 persons were randomly assigned, and 98 654 were included in intention-to-screen analyses: 20 552 in the screening group and 78 102 in the no-screening group. Participation with screening was 61.4% in men and 64.7% in women. In men, the 23-year cumulative risk for CRC was 4.3% in the screening group and 6.0% in the no-screening group, corresponding to a risk difference of −1.7 percentage points (95% CI, −2.2 to −1.2 percentage points). In women, the corresponding risks were 4.2% and 4.7%, yielding a risk difference of −0.5 percentage points (CI, −1.0 to −0.01 percentage points). In men, the 23-year cumulative risk for CRC death was 1.4% in the screening group and 2.2% in the no-screening group, corresponding to a risk difference of −0.8 percentage points (CI, −1.1 to −0.5 percentage points). In women, the corresponding risks were 1.3% and 1.4%, yielding a risk difference of −0.1 percentage points (CI, −0.3 to 0.1 percentage points). The effect was strongest for rectosigmoid cancer. The addition of fecal blood testing to sigmoidoscopy did not change screening benefits. Limitation: Follow-up through national registries. Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence more in men than in women and reduced CRC death only in men.

• Kaminski, Michal F; Kalager, Mette; Løberg, Magnus; Emilsson, Louise; Macios, Anna & Samy, Faye [Show all 22 contributors for this article] (2026). Long-term effects of colonoscopy screening on colorectal cancer incidence and mortality: a multicountry, population-based randomised controlled trial. The Lancet. ISSN 0140-6736. doi: 10.1016/s0140-6736(26)00508-8. Full text in Research Archive Show summary

  Background We previously reported the 10-year effects of colonoscopy screening on colorectal cancer incidence and mortality. Here, we report the effects after 13 years of follow-up. Methods In this multicountry, population-based randomised controlled trial, 84 583 men and women aged 55–64 years at enrolment from Norway, Poland, and Sweden were randomly allocated (1:2) to colonoscopy screening or no screening and analysed. The primary outcomes were colorectal cancer incidence and mortality after 10–15 years of follow-up in intention-to-screen analyses, with first analysis after 10 years, and repeated every other year or at longer intervals. This trial is registered with ClinicalTrials.gov, NCT00883792, and is ongoing. Findings At 13 years of follow-up, colorectal cancer incidence was 375 colorectal cancers (1·46%) of 28 217 individuals in the screening group and 912 colorectal cancers (1·80%) of 56 366 individuals in the no-screening group. The risk ratio (RR) was 0·81 (95% CI 0·71–0·90) in intention-to-screen analyses and 0·55 (0·33–0·81) in per-protocol analyses. The risk for proximal colorectal cancer was 129 (0·51%) in the screening group versus 283 (0·56%) in the no-screening group (RR 0·91 [0·71–1·09]), and the risk for distal colorectal cancer was 224 (0·87%) in the screening group versus 563 (1·11%) in the no-screening group (RR 0·79 [0·65–0·89]; interaction p<0·0001). In men, the colorectal cancer risk was 214 (1·69%) of 14 154 in the screening group and 541 (2·19%) of 28 247 in the no-screening group (RR 0·77 [0·64 to –0·88]); in women, the risk was 161 (1·24%) of 14 063 in the screening group versus 371 (1·43%) of 28 119 in the no-screening group (RR 0·87 [0·70 to 1·02]; interaction p<0·0001). Colorectal cancer mortality was 106 (0·41%) of 28 217 in the screening group and 236 (0·47%) of 56 366 in the no-screening group (intention-to-screen RR 0·88 [0·68–1·08], per-protocol RR 0·70 [0·26–1·25]). The observed colorectal cancer mortality in the non-screening group (0·47%) was substantially lower than expected at the time of designing the trial (0·82%). Interpretation One colonoscopy significantly reduced colorectal cancer incidence but not mortality over 13 years. Colorectal cancer mortality was lower in both study groups than when the trial was designed.

• Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Avershina, Ekaterina; Botteri, Edoardo; Bucher-Johannessen, Cecilie & Knudsen, Markus Dines [Show all 14 contributors for this article] (2026). Alcohol consumption and colorectal carcinogenesis: an exploration of the gut microbial pathway as a potential mediator. European Journal of Nutrition. ISSN 1436-6207. 65(4), p. 1–18. doi: 10.1007/s00394-026-03960-6. Full text in Research Archive Show summary

  Background Alcohol consumption is one of the major risk factors of colorectal cancer (CRC), yet the mechanisms underlying this relationship, particularly the role of gut microbes, are not fully understood. Objective To study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake and colorectal lesions. Methods Screening participants with a positive faecal immunochemical test at ages 55–77 were eligible for the CRCbiome study. Alcohol intake was assessed using a validated, semi-quantitative food frequency questionnaire and linked with shotgun metagenome based gut microbial profiles to study associations with screen-detected colorectal lesions. The potential role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was examined using causal mediation analysis. Results Of 1468 participants with dietary data, 414 were diagnosed with advanced lesions. Alcohol intake was positively associated with advanced lesions in a dose-dependent manner (ptrend = 0.008), with odds ratio of 1.09 (95% confidence interval, 1.00, 1.19) per 10 g/day increase. Compared to non-consumers, those consuming alcohol were characterized by a distinct microbial profile, manifested as modest, but consistent, shifts in α- and β-diversity, and differentially abundant bacteria. A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria. Conclusion Alcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions.

• Schult, Anna Lisa; Hoff, Geir Svein; Randel, Kristin Ranheim; Huppertz-Hauss, Gert; Dalén, Eirin & Matapour, Senaria [Show all 8 contributors for this article] (2026). Endoscopist as a key determinant of patient pain: a sigmoidoscopy screening model for unbiased assessment. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 61(6), p. 589–597. doi: 10.1080/00365521.2026.2646941. Full text in Research Archive Show summary

  Background Despite increasing standardization of training and growing attention to quality in lower gastrointestinal endoscopy, patient-reported pain during sigmoidoscopy varies considerably. This study explored whether this variability arises from differences in endoscopist performance or patient characteristics. Methods This cross-sectional study included unsedated sigmoidoscopies performed between 2014 and 2019 within a population-based screening trial. Neither patients nor endoscopists selected each other. Pain was self-reported on a Likert scale: no pain, mild, moderate, severe. Patients were considered to have experienced pain if moderate or severe pain was reported. We used multivariable logistic regression to identify pain predictors, reporting odds ratios (ORs) and 95% confidence intervals (CI). Results A total of 23,483 sigmoidoscopies were performed (49.0% in men) by 47 endoscopists. Pain was reported by 607 (5.3%) men and 1612 (13.5%) women and varied substantially across endoscopists, ranging from 4.3 to 21.3%. Independent predictors of pain included young age, female sex, specific endoscopist, and presence of diverticula and inflammatory bowel disease. Greater endoscopist experience correlated with lower pain rate (OR 0.82 per additional year of experience, 95% CI 0.79–0.85). Pain was associated with lower examination completion rate (OR 0.33, 95% CI 0.29–0.37) and a trend towards a lower adenoma detection rate (ADR; OR 0.91, 95% CI 0.79–1.04). Conclusion In this large study of unsedated sigmoidoscopies, the specific endoscopist strongly predicted patient-reported pain. Pain was linked to lower completion rates and ADR. Findings support ongoing quality monitoring and targeted training to minimize pain and improve outcomes.

• Rognstad, Øyvind Bakken; Botteri, Edoardo; Hoff, Geir Svein; Bretthauer, Michael; Nguyen, Dung-Hong & Schult, Anna Lisa [Show all 8 contributors for this article] (2026). Use of claims data to identify adverse events after colonoscopy in a randomised colorectal cancer screening trial in Norway: a cross-sectional study. BMJ Open. 16(1), p. 1–8. doi: 10.1136/bmjopen-2025-109883. Full text in Research Archive Show summary

  Objectives Accurate identification of adverse events after colonoscopy is essential for quality assurance in colorectal cancer (CRC) screening. Review of medical records is labour intensive as adverse events are infrequent. The object of this study was to investigate the accuracy of claims data in identifying adverse events after colonoscopy in CRC screening. Design Cross-sectional, retrospective. Setting and participants Males and females aged 50–74 years were randomised to once-only sigmoidoscopy or biennial faecal immunochemical test in a CRC screening trial at two screening centres in Norway. Participants in the present study underwent follow-up colonoscopy from 2012 to April 2020 after initial positive screening test. We reviewed medical records for adverse events within 30 days following 11 205 colonoscopies. Primary and secondary outcome measures The primary outcome of the study was to assess the sensitivity of claims data from the Norwegian Patient Registry to identify lower gastrointestinal bleeding using emergency contact International Statistical Classification of Diseases and Related Health Problems 10th Revision diagnostic code sets under two definitions: a stringent definition (codes explicitly identifying bleeding) and a broad definition (including suggestive codes). Secondary outcome measures included the sensitivity to identify perforation using a stringent and a broad definition. Additionally, we assessed whether incorporating procedure codes and non-emergency contacts improved accuracy. Results 87 cases of lower gastrointestinal bleeding and eight perforations were confirmed. Sensitivity for bleeding differed between the centres (p<0.001). At centre 1, sensitivity was 48.6% (95% CI 31.9% to 65.6%) using the stringent and 89.2% (95% CI 74.6% to 97.0%) using the broad definition. At centre 2, sensitivity was 36.0% (95% CI 22.9% to 50.8%) and 50.0% (95% CI 35.5% to 64.5%), respectively. Combined sensitivity for perforation was 37.5% (95% CI 8.5% to 75.5%) using the stringent and 62.5% (95% CI 24.5% to 91.5%) using the broad definition. Adding procedure codes and non-emergency contacts slightly increased sensitivity but increased false positives. Conclusions Use of claims data underestimated adverse event rates following colonoscopy. Difference in coding practice across hospitals underscores the need for standardised reporting in screening programmes. Trial registration number NCT01538550 .

• Holte, Silje Stensholt; Avaliani, Natalia; Hoff, Geir Svein; Kazaryan, Airazat M.; Jaioun, Keson & Lauzikas, Giedrius [Show all 7 contributors for this article] (2025). Effect of psyllium husk on low anterior resection syndrome after rectal cancer surgery—a pilot prospective cohort study. Frontiers in Surgery. 12. doi: 10.3389/fsurg.2025.1686486. Full text in Research Archive Show summary

  Introduction Low anterior resection syndrome (LARS) is a frequent, undesired consequence of rectal cancer surgery. Psyllium husk has been suggested as a nutritional supplement in the management of LARS, but without trial-based evidence of its effect. In preparation of a randomized clinical trial, this pilot study aimed to estimate the effect of Psyllium husk in patients with LARS, determining the treatment duration required to observe the effect and assess patient compliance. Methods This single arm phase II study included patients with LARS score &gt;20 ten months or more after rectal resection. Patients who consented to participate were given 3.66 g Psyllium husk fiber twice daily for 56 days. The primary endpoint was severity of bowel dysfunction using the LARS score. The secondary endpoint was quality of life (QoL) using EQ-VAS score in the EQ-5D-5L questionnaire. A reduction of 7 points in LARS score was considered clinically relevant. Questionnaires and scores were collected on paper day 0 (baseline), day 28 and day 56. Results 22 patients were assigned to the intervention and included in the analysis. The average age was 65.3 (SD 10.4), the average LARS score at baseline was 35,7 (SD 3.5), four patients had received radiotherapy. The proportion of patients with a LARS score reduction of 7 points or more compared to baseline was 50.0% at day 28 (11/22) and 50.0% at day 56 (10/20). The mean reduction in LARS scores from baseline to 8 weeks of treatment was 7.7 points. At day 28, the proportion of patients with a QoL score (EQ-VAS score) increase of 10 points or more was 36.4% (8/22), increasing to 60.0% (12/20) by day 56. Two patients dropped out after 4 weeks of treatment, one due to taste and consistency of the supplement and one due to inconsistently beneficial effect. Conclusions Psyllium husk appears to clinically significantly improve both bowel dysfunction and QoL in rectal cancer patients suffering from LARS. This study highlights the need for further systematic research, and provides a strong basis for a well-designed RCT.

• Hoff, Geir Svein; Bernklev, Tomm; Kvaløy, Jan Terje; Gibbs, Charlotte Christine & Reitsma, Laurens Cornelus (2025). Patients With Persistent Hashimoto-Related Symptoms. Dilemmas in Advice-Giving and Self-Selection for Thyroidectomy. An Observational Study. Endocrine Practice. ISSN 1530-891X. 31(7), p. 906–912. doi: 10.1016/j.eprac.2025.04.007. Full text in Research Archive Show summary

  Objective Some Hashimoto-related symptoms, persistent despite medically obtained euthyroidism, are believed to be related to autoimmunity. Total thyroidectomy has proved beneficial for patient-reported outcome measures (PROMs), but with a certain risk of complications. Selection criteria for surgery have not been defined. Molecular evidence supporting an autoimmune cause is lacking, and a placebo effect of surgery cannot be excluded. Short of selection criteria for thyroidectomy and no pathophysiologic model to adequately explain persistent symptoms, we wanted to look into factors that may be related to patients’ decision for surgery, thus aiming to facilitate patient-physician communication on treatment for persistent Hashimoto-related symptoms. Methods A total of 177 patients with persistent Hashimoto disease-related symptoms and highly motivated for thyroidectomy completed an 18-month watchful waiting period with biannual consultations before being offered thyroidectomy. PROMs were monitored before and after surgery. Results After 18 months of watchful waiting, 131 (74%) of 177 patients proceeded to thyroidectomy whereas 46 declined surgery. There was no difference between the surgery and no-surgery groups regarding sex, age, and thyroid peroxidase antibody levels at 18 months watchful waiting. Compared with the no-surgery group, PROM scores were consistently poorer in the surgery group for all domains in the PROM questionnaires used. Conclusions A grace period of 18 months with biannual follow-up before thyroidectomy may be useful to modify exposure to surgery carrying a certain risk of complications. At 18 months, the fatigue score stands out as the most important factor influencing the odds for maintaining a choice to have surgery.

• Lien, Gro Irene; Jaioun, Keson; Bock, Gunter Ernst Konrad; Løvall, Camilla; Vollen, Berit & Lauzikas, Giedrius [Show all 7 contributors for this article] (2025). Association between the protrusion of ileostomies and peristomal dermatitis: an observational study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 60(4), p. 322–326. doi: 10.1080/00365521.2025.2475092. Full text in Research Archive Show summary

  This is an observational study to explore possible changes in end-ileostomy stoma protrusion through years of modified surgical methods. Materials and methods Patients with permanent end-ileostomy were eligible for inclusion. Patients were recruited from two outpatient clinics in South-East Norway and from the Norwegian society for patients with ostomy (NORILCO). Stoma protrusion was measured in upright and supine positions by study nurse (outpatient cohort) or by the patient (NORILCO cohort). Clinical information was obtained through patients’ questionnaire replies. For analyses, a pragmatic 24-hour ileostomy protrusion score was created, where 16/24 of upright measurement constituted protrusion during daytime and 8/24 of supine measurement protrusion at sleep. Results 93 participated in the study, 32 from outpatient clinics and 61 from NORILCO. The outpatients cohort had shorter stoma history than the NORILCO cohort. There was a weak positive correlation between stoma protrusion and years since stoma was created (rs =0.303, p < 0.003), but stoma protrusion appeared not to be related to surgical method. In both groups, there was some reduction in stoma protrusion from upright to supine position, from 2.5 cm upright in both groups to 2.0–2.2 cm supine. Conclusions Stoma protrusion was positively associated with years since stoma was created, but not with surgical method (laparotomy or laparoscopy). A functional 24-hour protrusion score may reduce the effect of clustering of measurements due to end-digit preferences and a preoccupied focus on 2 cm as the tipping point for skin problems. Further and larger studies are needed with special attention to reduce selection bias.

• Nafisi, Sara; Støer, Nathalie Charlotte; Veierød, Marit Bragelien; Randel, Kristin R.; Hoff, Geir & Löfling, Leif Lukas [Show all 8 contributors for this article] (2024). Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway. American Journal of Gastroenterology. ISSN 0002-9270. 119(7), p. 1402–1411. doi: 10.14309/ajg.0000000000002695. Full text in Research Archive Show summary

  Objectives: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). Methods: In this nationwide cohort study, we identified individuals aged ≥50 years residing for 6 months or more in Norway in 2004-2018, and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. Additionally, we calculated the number of CRCs potentially averted by low-dose aspirin use. Results: We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs. never use was associated with lower CRC risk (hazard ratios [HR]=0.87, 95% confidence intervals [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR=0.79; 95%CI 0.74-0.84) than regionally advanced (HR=0.89; 95%CI 0.85-0.92) and localized CRC (HR=0.93; 95%CI 0.87-1.00; Pheterogeneity=0.001). A significant trend was found between duration of current use and CRC risk: HR=0.91 (95%CI 0.86-0.95) for <3 years, HR=0.85 (0.80-0.91) for ≥3 and <5 years, and HR=0.84 (0.80-0.88) for ≥5 years of use vs. never use (Ptrend<0.001). For past use, HRs were 0.89 (95%CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs. never use (Ptrend<0.001). We estimated that aspirin use averted 1073 (95%CI 818-1338) CRCs in the study period. Conclusion: In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

• Hoff, Geir Svein; Bernklev, Tomm; Johnsen, Lene; Reitsma, Laurens Cornelus; Sina, Dirk & Lauzike, Andromeda [Show all 13 contributors for this article] (2024). Thyroidectomy for Euthyroid Patients with Hashimoto Disease and Persistent Symptoms: An Observational, Postrandomization Study. Journal of Thyroid Research. ISSN 2090-8067. 2024(1). doi: 10.1155/2024/5518720. Full text in Research Archive Show summary

  Background: Despite adequate hormone substitution in Hashimoto disease, some patients may have persistent symptoms with a possible autoimmune pathophysiology. A recent randomized trial (RCT) using patient-reported outcome measures as the primary endpoint showed benefit in total thyroidectomy, but at a cost of high complication rates. Objective: To verify results from the RCT in an observational study including a wider range of patients and explore means of predicting who may benefit from such surgery. Design: A total of 154 patients with Hashimoto disease, euthyroid with or without thyroid hormone substitution, and persistent Hashimoto-related symptoms were subjected to total thyroidectomy and followed for 18 months after surgery. The primary outcome was the General Health (GH) dimensional score in the Short Form-36 Health Survey (SF-36). Results: Eighteen months after surgery, a clinically significant improvement in GH was seen, similar to the findings in the previous RCT. Anti-TPO antibody titers were markedly reduced after surgery, but preoperative titers or other preoperative parameters could not predict the outcome of surgery. Three (1.9%) of 154 patients experienced permanent unilateral recurrent nerve palsy and six (3.9%) experienced hypoparathyroidism after surgery. Conclusions: Thyroidectomy had a beneficial symptom-reducing effect in euthyroid patients with Hashimoto disease and persistent symptoms. The pathophysiology of residual symptoms remains unclear, and surgical complication rates are high. If thyroidectomy is considered as a treatment option, it should be performed in dedicated centers with experienced endocrine surgeons and as part of further studies on persistent symptoms. This trial is registered with NCT-02319538.

• Randel, Kristin Ranheim; Schult, Anna Lisa; Botteri, Edoardo; Nawaz, Mobina; Nguyen, Dung-Hong & Holme, Øyvind [Show all 9 contributors for this article] (2024). Impact of inadequate bowel cleansing in sigmoidoscopy screening. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(8), p. 1002–1009. doi: 10.1080/00365521.2024.2364213. Full text in Research Archive Show summary

  Background and study aims: Long-time follow-up of sigmoidoscopy screening trials has shown reduced incidence and mortality of colorectal cancer (CRC), but inadequate bowel cleansing may hamper efficacy. The aim of this study was to assess the impact of bowel cleansing quality in sigmoidoscopy screening. Patients and methods: Individuals 50 to 74 years old who had a screening sigmoidoscopy in a population-based Norwegian, randomized trial between 2012 and 2019, were included in this cross-sectional study. The bowel cleansing quality was categorised as excellent, good, partly poor, or poor. The effect of bowel cleansing quality on adenoma detection rate (ADR) and referral to colonoscopy was evaluated by fitting multivariable logistic regression models. Results: 35,710 individuals were included. The bowel cleansing at sigmoidoscopy was excellent in 20,934 (58.6%) individuals, good in 6580 (18.4%), partly poor in 7097 (19.9%) and poor in 1099 (3.1%). The corresponding ADRs were 17.0%, 16.6%, 14.5%, and 13.0%. C

• Bucher-Johannessen, Cecilie; Senthakumaran, Thulasika; Avershina, Ekaterina; Birkeland, Einar Elvbakken; Hoff, Geir Svein & Bemanian, Vahid [Show all 8 contributors for this article] (2024). Species-level verification of Phascolarctobacterium association with colorectal cancer. mSystems. 9(10). doi: 10.1128/msystems.00734-24. Full text in Research Archive Show summary

  We have previously demonstrated an association between increased abundance of Phascolarctobacterium and colorectal cancer (CRC) and adenomas in two independent Norwegian cohorts. Here we seek to verify our previous findings using new cohorts and methods. In addition, we characterize lifestyle and sex specificity, the functional potential of the Phascolarctobacterium species, and their interaction with other microbial species. We analyze Phascolarctobacterium with 16S rRNA sequencing, shotgun metagenome sequencing, and species-specific qPCR, using 2350 samples from three Norwegian cohorts-CRCAhus, NORCCAP, and CRCbiome-and a large publicly available data set, curatedMetagenomicData. Using metagenome-assembled genomes from the CRCbiome study, we explore the genomic characteristics and functional potential of the Phascolarctobacterium pangenome. Three species of Phascolarctobacterium associated with adenoma/CRC were consistently detected by qPCR and sequencing. Positive associations with adenomas/CRC were verifi

• Botteri, Edoardo; Peveri, Giulia; Berstad, Paula Marianna; Bagnardi, Vincenzo; Hoff, Geir Svein & Heath, Alicia K. [Show all 44 contributors for this article] (2024). Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition. European Journal of Epidemiology (EJE). ISSN 0393-2990. 39, p. 147–159. doi: 10.1007/s10654-023-01059-4. Full text in Research Archive Show summary

  In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers.including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others.using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95.0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI . 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07.1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65.0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

• Rognstad, Øyvind Bakken; Botteri, Edoardo; Hoff, Geir Svein; Bretthauer, Michael; Gulichsen, Elisabeth Haagensen & Frigstad, Svein Oskar [Show all 8 contributors for this article] (2024). Adverse events after colonoscopy in a randomised colorectal cancer screening trial. BMJ open gastroenterology. 11(1). doi: 10.1136/bmjgast-2024-001471. Full text in Research Archive Show summary

  Objective: Colonoscopy-related adverse events increase the burden of colorectal cancer (CRC) screening. This cross-sectional study evaluates adverse events during and after colonoscopy in a large, randomised CRC screening trial in Norway comparing sigmoidoscopy to immunochemical testing for faecal blood. Methods: We included all individuals who underwent colonoscopy at two screening centres between 2012 and 2020. From medical records, we retrieved data on adverse events during and within 30 days after colonoscopy and classified them according to the American Society for Gastrointestinal Endoscopy lexicon for endoscopic adverse events. Multivariable logistic regression models were fitted to identify risk factors for adverse events. Results: Of the 10 244 included individuals, 242 (2.4%) had at least one adverse event that was possibly, probably, or definitively related to the colonoscopy. 188 (1.8%) had mild adverse events, 50 (0.49%) had moderate, 3 (0.03%) had severe, and 1 had a fatal adverse event. The m

• Randel, Kristin Ranheim; Botteri, Edoardo; Lange, Thomas de; Schult, Anna Lisa; Eskeland, Sigrun Losada & El-Safadi, Badboni [Show all 11 contributors for this article] (2024). Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 61(1), p. 122–131. doi: 10.1111/apt.18314. Full text in Research Archive Show summary

  Background: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries. Aims: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial. Methods: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g. Results: At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702

• Juul, Frederik Emil; Cross, Amanda J.; Schoen, Robert E.; Senore, Carlo; Pinsky, Paul F. & Miller, Eric A. [Show all 17 contributors for this article] (2024). Effectiveness of Colonoscopy Screening vs Sigmoidoscopy Screening in Colorectal Cancer. JAMA Network Open. 7(2). doi: 10.1001/jamanetworkopen.2024.0007. Full text in Research Archive Show summary

  Importance: Randomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking. Objective: To estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy. Design, setting, and participants: This comparative effectiveness simulation study pooled data on 358 204 men and women randomly assigned to sigmoidoscopy screening or usual care in 4 randomized sigmoidoscopy screening trials conducted in Norway, Italy, the US, and UK with inclusion periods in the years 1993 to 2001. The primary analysis of the study was conducted from January 19 to December 30, 2021. Intervention: Invitation to endoscopic screening. Main outcomes and measures: Primary outcomes were CRC incidence and mortality. Using pooled 15-year follow-up data, colonoscopy screening effectiveness was estimate

• Bucher-Johannessen, Cecilie; Birkeland, Einar Elvbakken; Vinberg, Elina; Bemanian, Vahid; Hoff, Geir Svein & Berstad, Paula [Show all 7 contributors for this article] (2023). Long-term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16S rRNA and metagenome sequencing. Frontiers in Oncology. 13. doi: 10.3389/fonc.2023.1183039. Full text in Research Archive Show summary

  Background: The microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross-sectional studies. However, there is a lack of studies using prospectively collected samples. Methods: From the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the samples and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity and differential abundance. Results: Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was associated with time to CRC diagnosis. Conclusion: Using a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.

• Schult, Anna Lisa; Hoff, Geir Svein; Holme, Øyvind; Botteri, Edoardo; Seip, Birgitte Karen Berggreen & Randel, Kristin Ranheim [Show all 12 contributors for this article] (2023). Colonoscopy quality improvement after initial training: A cross-sectional study of intensive short-term training. Endoscopy International Open. 11(1), p. E117–E127. doi: 10.1055/a-1994-6084. Full text in Research Archive Show summary

  Background and study aims High-quality is crucial for the effectiveness of colonoscopy and can be achieved by high-quality training and verified with assessment of key performance indicators (KPIs) for colonoscopy such as cecum intubation rate (CIR), adenoma detection rate (ADR) and adequate polyp resection. Typically, trainees achieve adequate CIR after 275 procedures, but little is known about learning curves for KPIs after initial training. Methods This cross-sectional study includes work-up colonoscopies after a positive screening test with fecal occult blood testing (FIT) or sigmoidoscopy, performed by either trainees after 300 training colonoscopies or by consultants. Outcome measures were KPIs. We assessed inter-endoscopist variation in trainees and learning curves for trainees as a group. We also compared KPIs for trainees and consultants as a group. Results Data from 6,655 colonoscopies performed by 21 trainees and 921 colonoscopies performed by 17 consultants were included. Most trainees achieved target standards for main KPIs. With time, trainees shortened cecum intubation time and withdrawal time without decreasing their ADR, reduced the proportion of painful colonoscopies, and increased the adequate polyp resection rate (all P < 0.01). Compared to consultants, trainees had higher CIR (97.7 % vs. 96.3 %, P = 0.02), ADR after positive FIT (57.6 % vs. 50.3 %, P < 0.01), and proximal ADR after sigmoidoscopy screening (41.1 % vs. 29.8 %; P < 0.01), higher adequate polyp resection rate (94.9 % vs. 93.1 %, P = 0.01) and fewer serious adverse events (0.65 % vs. 1.41 %, P = 0.02). Conclusions Trainees performed high-quality colonoscopies and achieved international target standards. Several KPIs continuously improved after initial training. Trainees outperformed consultants on several KPIs.

• Nafisi, Sara; Randel, Kristin Ranheim; Støer, Nathalie Charlotte; Veierød, Marit Bragelien; Hoff, Geir Svein & Holme, Øyvind [Show all 8 contributors for this article] (2023). Association between use of low-dose aspirin and detection of colorectal polyps and cancer in a screening setting. Digestive and Liver Disease. ISSN 1590-8658. 55, p. 1126–1132. doi: 10.1016/j.dld.2023.01.156. Full text in Research Archive Show summary

  Background: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated. Methods: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions. Conclusion: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs.

• Birkeland, Einar Elvbakken; Ferrero, Giulio; Pardini, Barbara; Umu, Sinan Ugur; Tarallo, Sonia & Bulfamante, Sara [Show all 10 contributors for this article] (2023). Profiling small RNAs in fecal immunochemical tests: is it possible? Molecular Cancer. 22:161(1), p. 1–7. doi: 10.1186/s12943-023-01869-w. Full text in Research Archive Show summary

  Fecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT especially for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of FIT samples, would be ideal due to their widespread use. In the present study, we assessed the feasibility of applying small RNA sequencing to measure human miRNAs in FIT leftover buffer in samples from two European screening populations. We showed robust detection of miRNAs with profiles similar to those obtained from specimens sampled using the established protocol of RNA stabilizing buffers, or in long-term archived samples. Detected miRNAs exhibited differential abundances for CRC, advanced adenoma, and control samples that were consistent for FIT and RNA-stabilizing buffers. Interestingly, the sequencing data also allowed for concomitant evaluation of small RNA-based microbial profiles. We demonstrated that it is possible to explore the human miRNome in FIT leftover samples across populations and envision that the analysis of small RNA biomarkers can complement the FIT in large scale screening settings.

• Bresalier, Robert S.; Senore, Carlo; Young, Graeme P.; Allison, James; Benamouzig, Robert & Benton, Sally [Show all 47 contributors for this article] (2023). An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles. Gut. ISSN 0017-5749. 72. doi: 10.1136/gutjnl-2023-329701. Full text in Research Archive Show summary

  Objective: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. Design: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Results: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. Conclusion: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

• Hoff, Geir Svein; Bernklev, Tomm; Johnsen, Lene; Reitsma, Laurens Cornelus; Sina, Dirk & Lauzike, Andromeda [Show all 14 contributors for this article] (2023). Thyroidectomy for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms. Annals of Internal Medicine. ISSN 0003-4819. 177(1), p. 101–103. doi: 10.7326/M23-1593. Full text in Research Archive
• Knudsen, Markus Dines; Kværner, Ane Sørlie; Botteri, Edoardo; Holme, Øyvind; Hjartåker, Anette & Song, Mingyang [Show all 10 contributors for this article] (2022). Lifestyle predictors for inconsistent participation to fecal based colorectal cancer screening. BMC Cancer. 22(172). doi: 10.1186/s12885-022-09287-9. Full text in Research Archive Show summary

  Background: Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening. Method: We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations). Results: Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p

• Botteri, Edoardo; Hoff, Geir; Randel, Kristin Ranheim; Holme, Øyvind; Lange, Thomas de & Bernklev, Tomm [Show all 16 contributors for this article] (2022). Characteristics of nonparticipants in a randomised colorectal cancer screening trial comparing sigmoidoscopy and faecal immunochemical testing. International Journal of Cancer. ISSN 0020-7136. 151(3), p. 361–371. doi: 10.1002/ijc.34025. Full text in Research Archive Show summary

  Public health systems should guarantee universal access to health care services, including cancer screening. We assessed whether certain population subgroups were underrepresented among participants in colorectal cancer screening with sigmoidoscopy and faecal immunochemical testing (FIT). Between 2012 and 2019, about 140 000 individuals aged 50 to 74 years were randomly invited to once-only sigmoidoscopy or first round of FIT screening. Our study included 46 919 individuals invited to sigmoidoscopy and 70 019 to FIT between 2012 and 2017. We used logistic regression models to evaluate if demographic and socioeconomic factors and use of certain drugs were associated with participation. Twenty-four thousand one hundred and fifty-nine (51.5%) individuals attended sigmoidoscopy and 40 931 (58.5%) FIT screening. Male gender, young age, low education and income, being retired or unemployed, living alone, being an immigrant, long driving time to screening centre, and use of antidiabetic and psychotropic drugs were associated with low participation in both screening groups. Many of these factors also predicted low acceptance of colonoscopy after positive FIT. While male gender, young age and living alone were more strongly associated with nonparticipation in FIT than sigmoidoscopy, low education and income, being retired or immigrant and long driving time were more strongly associated with nonparticipation in sigmoidoscopy than FIT. In conclusion, participation was lower in sigmoidoscopy than FIT. Predictors of nonparticipation were similar between arms. However, low socioeconomic status, being an immigrant and long driving time affected participation more in sigmoidoscopy screening, suggesting that FIT may guarantee more equal access to screening services than sigmoidoscopy.

• Juul, Frederik Emil; Cross, Amanda J.; Schoen, Robert E.; Senore, Carlo; Pinsky, Paul & Miller, Eric [Show all 17 contributors for this article] (2022). 15-Year Benefits of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality : A Pooled Analysis of Randomized Trials. Annals of Internal Medicine. ISSN 0003-4819. 175(11), p. 1525–1533. doi: 10.7326/M22-0835. Full text in Research Archive Show summary

  Background: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain. Objective: To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality. Design: Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening. Setting: Norway, the United States, the United Kingdom, and Italy. Participants: Women and men aged 55 to 64 years at enrollment. Intervention: Sigmoidoscopy screening. Measurements: Primary end points were cumulative incidence rate ratio (IRR) and mortality rate ratio (MRR) and rate differences after 15 years of follow-up comparing screening versus usual care in intention-to-treat analyses. Stratified analyses were done by sex, cancer site, and age at screening. Results: Analyses comprised 274 952 persons (50.7% women), 137 493 in the screening and 137 459 in the usual care group. Screening attendance was 58% to 84%. After 15 years, the rate difference for CRC incidence was 0.51 cases (95% CI, 0.40 to 0.63 cases) per 100 persons and the IRR was 0.79 (CI, 0.75 to 0.83). The rate difference for CRC mortality was 0.13 deaths (CI, 0.07 to 0.19 deaths) per 100 persons, and the MRR was 0.80 (CI, 0.72 to 0.88). Women had less benefit from screening than men for CRC incidence (IRR for women, 0.84 [CI, 0.77 to 0.91]; IRR for men, 0.75 [CI, 0.70 to 0.81]; P = 0.032 for difference) and mortality (MRR for women, 0.91 [CI, 0.77 to 1.17]; MRR for men, 0.73 [CI, 0.64 to 0.83]; P = 0.025 for difference). There was no statistically significant difference in screening effect between persons aged 55 to 59 years and those aged 60 to 64 years. Limitation: Data from the U.K. trial were less granular because of privacy regulations. Conclusion: This pooled analysis of all large randomized trials of sigmoidoscopy screening demonstrates a significant and sustained effect of sigmoidoscopy on CRC incidence and mortality for 15 years.

• Botteri, Edoardo; Peveri, Giulia; Berstad, Paula; Bagnardi, Vincenzo; Chen, Sairah Lai Fa & Sandanger, Torkjel M [Show all 43 contributors for this article] (2022). Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition. American Journal of Gastroenterology. ISSN 0002-9270. 118(4), p. 702–711. doi: 10.14309/ajg.0000000000002065. Full text in Research Archive Show summary

  Introduction: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multi-country European cohort. Methods: We used baseline and follow-up questionnaire data from the EPIC cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index and physical activity collected at the two timepoints. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. Median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI>11), those in the bottom tertile at follow-up (HLI≤9) had a higher CRC risk (HR 1.34; 95%CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95%CI 0.59-1.00) than those remaining in the bottom tertile. Discussion: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

• Kirkøen, Benedicte; Berstad, Paula; Hoff, Geir; Bernklev, Tomm; Randel, Kristin Ranheim & Holme, Øyvind [Show all 9 contributors for this article] (2022). Type and Severity of Mental Illness and Participation in Colorectal Cancer Screening. American Journal of Preventive Medicine. ISSN 0749-3797. 64(1), p. 76–85. doi: 10.1016/j.amepre.2022.08.011. Full text in Research Archive Show summary

  Introduction: The effectiveness of colorectal cancer screening programs depends on the participation rate. This study examined the association between type and severity of mental illness and colorectal cancer screening participation. Methods: Between 2012 and 2017, a total of 46,919 individuals were invited to sigmoidoscopy screening in Norway, and 70,019 were invited to fecal immunochemical testing. In 2022, logistic regression was used to evaluate the association between the use of antipsychotics, anxiolytics, hypnotics, and antidepressants in the year preceding the screening invitation and screening participation, adjusted for demographic and socioeconomic factors. Defined daily doses of individual drugs were used to assess dose‒response relationships. Results: Overall, 19.2% (24.8% of women, 13.4% of men) of all invitees used at least 1 psychotropic medication. Nonparticipation in the 2 arms combined was associated with the use of anxiolytics (60.7% in users vs 43.2% in nonusers; OR=1.53; 95% CI=1.45, 1.62) and antipsychotics (64.3% vs 43.8%; OR=1.41; 95% CI=1.30, 1.53) and increased with higher doses for both drugs. Hypnotics and antidepressants were only weakly associated with nonparticipation in higher doses. Participation rates were 57.3%, 52.3%, 42.9%, and 35.4% in those prescribed 0, 1, 2, and 3-4 classes of psychotropic medications, respectively. The associations between the use of psychotropic medications and nonparticipation were similar for the 2 screening tests. Conclusions: These findings show significant disparities in colorectal cancer screening participation for individuals with mental illness, independent of the screening method. Moreover, screening participation varied depending on the type and severity of mental illness. Targeted interventions are warranted to ensure that people with mental illness are supported to access the benefits of colorectal cancer screening.

• Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Vinberg, Elina; Hoff, Geir; Hjartåker, Anette & Rounge, Trine Ballestad [Show all 7 contributors for this article] (2022). Associations of red and processed meat intake with screen-detected colorectal lesions. British Journal of Nutrition. ISSN 0007-1145. p. 1–36. doi: 10.1017/S0007114522002860. Full text in Research Archive Show summary

  Limited data exist regarding the role of meat consumption in early-stage colorectal carcinogenesis. We examined associations of red and processed meat intake with screen-detected colorectal lesions in immunochemical fecal occult blood test (FIT)-positive participants, enrolled in the Norwegian CRCbiome study during 2017-2021, aged 55-77 years. Absolute and energy-adjusted intakes of red and processed meat (combined and individually) were assessed using a validated, semiquantitative food frequency questionnaire. Associations between meat intake and screen-detected colorectal lesions were examined using multinomial logistic regression analyses with adjustment for key covariates. Of 1,162 participants with available dietary data, 319 (27%) presented with advanced colorectal lesions at colonoscopy. High vs low energy-adjusted intakes of red and processed meat combined, as well as red meat alone, were borderline to significantly positively associated with advanced colorectal lesions (ORs (95% CIs) of 1.24 (0.98, 1.57) and 1.34 (1.07, 1.69), respectively). A significant dose-response-relationship was also observed for absolute intake levels (OR (95% CI) of 1.32 (1.09, 1.60) per 100 g/day increase in red and processed meat). For processed meat, no association was observed between energy-adjusted intakes and advanced colorectal lesions. A significant positive association was, however, observed for the small proportion of participants (10%) with absolute intake levels ≥100 vs <50 g/day (OR (95% CI) of 1.19 (1.09, 1.31)). In summary, high intakes of red and processed meat were associated with presence of advanced colorectal lesions at colonoscopy in FIT-positive participants. The study demonstrates a potential role of using dietary data to improve the performance of FIT-based screening.

• Berthelsen, Mona; Berstad, Paula; Randel, Kristin Ranheim; Hoff, Geir; Natvig, Erik & Holme, Øyvind [Show all 7 contributors for this article] (2022). The impact of driving time on participation in colorectal cancer screening with sigmoidoscopy and faecal immunochemical blood test. Cancer Epidemiology. ISSN 1877-7821. 80. doi: 10.1016/j.canep.2022.102244. Full text in Research Archive Show summary

  Background: High participation rates are important for a colorectal cancer (CRC) screening programme to be effective. Having a long travelling distance to screening centres may impede participation. Methods: We analysed the association between driving time from home address to screening centre and participation among individuals invited to screening with faecal immunochemical test (FIT) (n = 68,624) or sigmoidoscopy (n = 46,076) in a randomized trial in Norway in 2012-17. Two screening centres were involved. We fitted multiple logistic regression models, adjusted for demographic, socioeconomic and health characteristics, and reported odds ratios (OR) with 95% confidence intervals (CI). Results: Participation rates were 58.9 % (n = 40,445) for FIT and 51.9 % (n = 23,911) for sigmoidoscopy. In sigmoidoscopy, participation was 56.9 % and 47.9 % in those living < 20 and > 60 min by car from the screening centres, respectively. For each 10 min driving time increase, OR for participating in sigmoidoscopy screening was 0.93 (95 % CI 0.91-0.95). There was a significant difference between the two screening centres (p-value for heterogeneity <0.001). Participation in FIT screening were 61.2 % and 57.1 % in those with < 20 and > 60 min driving time, respectively, and the OR was 0.98 (95 % CI 0.96-0.99) for each 10 min increase (heterogeneity between screening methods, P-value <0.001). Among those with a positive FIT, compliance to colonoscopy was higher in those living < 20 compared to > 60 min from the centres (95.1 % vs. 92.9 %, respectively, OR 0.86; 95 % CI 0.77-0.93 for each 10 min increase). Conclusions: Driving time to screening centre was a significant predictor of participation, mainly in sigmoidoscopy. There were local differences in the impact of driving time on participation. Driving time also affected compliance to colonoscopy after a positive FIT. When planning a CRC screening programme, one should consider offering people living far from screening sites special assistance to facilitate their participation.

• Pedersen, Ina Borgenheim; Rawa-Goleblewska, Anna; Calderwood, Audrey H.; Brix, Lone D.; Grode, Louise B. & Botteri, Edoardo [Show all 17 contributors for this article] (2022). Complete Polyp Resection with Cold versus Hot snare Polypectomy for Polyps sized 4-9 mm: A randomized controlled trial. Endoscopy. ISSN 0013-726X. 54(10), p. 961–969. doi: 10.1055/a-1734-7952. Full text in Research Archive Show summary

  Background: Endoscopic screening with polypectomy reduces the incidence of colorectal cancer (CRC). Incomplete polyp removal may attenuate the effect of screening. This randomized trial compared cold snare polypectomy (CSP) with hot snare polypectomy (HSP) in terms of complete polyp resection. Methods: We included patients ≥ 40 years of age at eight hospitals in four countries who had at least one non-pedunculated polyp of 4-9 mm detected at colonoscopy. Patients were randomized 1:1 to CSP or HSP. Biopsies from the resection margins were obtained systematically after polypectomy in both groups. We hypothesized that CSP would be non-inferior to HSP, with a non-inferiority margin of 5 %. Logistic regression models were fitted to identify the factors explaining incomplete resection. Results: 425 patients, with 601 polyps, randomized to either CSP or HSP were included in the analysis. Of 318 polyps removed by CSP and 283 polyps removed by HSP, 34 (10.7 %) and 21 (7.4 %) were incompletely resected, respectively, with an adjusted risk difference of 3.2 % (95 %CI -1.4 % to 7.8 %). There was no difference between the groups in terms of post-polypectomy bleeding, perforation, or abdominal pain. Independent risk factors for incomplete removal were serrated histology (odds ratio [OR] 3.96; 95 %CI 1.63 to 9.66) and hyperplastic histology (OR 2.52; 95 %CI 1.30 to 4.86) in adjusted analyses. Conclusion: In this randomized trial, non-inferiority for CSP could not be demonstrated. Polyps with serrated histology are more prone to incomplete resection compared with adenomas. CSP can be used safely for small polyps in routine colonoscopy practice.

• Bretthauer, Michael; Løberg, Magnus; Wieszczy, Paulina; Kalager, Mette; Emilsson, Louise & Garborg, Kjetil Kjeldstad [Show all 21 contributors for this article] (2022). Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. New England Journal of Medicine. ISSN 0028-4793. 387(17), p. 1547–1556. doi: 10.1056/NEJMoa2208375. Full text in Research Archive Show summary

  Background: Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear. Methods: We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio to either receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause. Results: Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04). Conclusions: In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.).

• Schult, Anna Lisa; Botteri, Edoardo; Hoff, Geir; Holme, Øyvind; Bretthauer, Michael & Randel, Kristin Ranheim [Show all 13 contributors for this article] (2021). Women require routine opioids to prevent painful colonoscopies: a randomised controlled trial. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 56(12), p. 1480–1489. doi: 10.1080/00365521.2021.1969683. Full text in Research Archive Show summary

  Background: Women are at high risk for painful colonoscopy. Pain, but also sedation, are barriers to colorectal cancer (CRC) screening participation. In a randomised controlled trial, we compared on-demand with pre-colonoscopy opioid administration to control pain in women at CRC screening age. Methods: Women, aged 55-79 years, attending colonoscopy at two Norwegian endoscopy units were randomised 1:1:1 to (1) fentanyl on-demand, (2) fentanyl prior to colonoscopy, or (3) alfentanil on-demand. The primary endpoint was procedural pain reported by the patients on a validated four-point Likert scale and further dichotomized for the study into painful (moderate or severe pain) and non-painful (slight or no pain) colonoscopy. Secondary endpoints were: willingness to repeat colonoscopy, adverse events, cecal intubation time and rate, and post-procedure recovery time. Results: Between June 2017 and May 2020, 183 patients were included in intention-to-treat analyses in the fentanyl on-demand group, 177 in the fentanyl prior to colonoscopy group, and 179 in the alfentanil on-demand group. Fewer women receiving fentanyl prior to colonoscopy reported a painful colonoscopy compared to those who were given fentanyl on-demand (25.2% vs. 44.1%, p

• Hoff, Geir; Botteri, Edoardo; Huppertz-Hauss, Gert; Kvamme, Jan-Magnus; Holme, Øyvind & Aabakken, Lars [Show all 13 contributors for this article] (2021). The effect of train-the-colonoscopy-trainer course on colonoscopy quality indicators. Endoscopy. ISSN 0013-726X. 53(12), p. 1229–1234. doi: 10.1055/a-1352-4583. Full text in Research Archive Show summary

  Background: Systematic training in colonoscopy is highly recommended; however, we have limited knowledge of the effects of "training-the-colonoscopy-trainer" (TCT) courses. Using a national quality register on colonoscopy performance, we aimed to evaluate the effects of TCT participation on defined quality indicators. Methods: This observational study compared quality indicators (pain, cecal intubation, and polyp detection) between centers participating versus not participating in a TCT course. Nonparticipating centers were assigned a pseudoparticipating year to match their participating counterparts. Results were compared between first year after and the year before TCT (pseudo)participation. Time trends up to 5 years after TCT (pseudo)participation were also compared. Generalized estimating equation models, adjusted for age, sex, and bowel cleansing, were used. Results: 11 participating and 11 nonparticipating centers contributed 18 555 and 10 730 colonoscopies, respectively. In participating centers, there was a significant increase in detection of polyps ≥ 5 mm, from 26.4 % to 29.2 % (P = 0.035), and reduction in moderate/severe pain experienced by women, from 38.2 % to 33.6 % (P = 0.043); no significant changes were found in nonparticipating centers. Over 5 years, 20 participating and 18 nonparticipating centers contributed 85 691 and 41 569 colonoscopies, respectively. In participating centers, polyp detection rate increased linearly (P = 0.003), and pain decreased linearly in women (P = 0.004). Nonparticipating centers did not show any significant time trend during the study period. Conclusions: Participation in a TCT course improved polyp detection rates and reduced pain experienced by women. These effects were maintained during a 5-year follow-up.

• Schult, Anna Lisa; Botteri, Edoardo; Hoff, Geir; Randel, Kristin Ranheim; Dalén, Eirin & Eskeland, Sigrun Losada [Show all 8 contributors for this article] (2021). Detection of cancers and advanced adenomas in asymptomatic participants in colorectal cancer screening: a cross-sectional study. BMJ Open. 11(7). doi: 10.1136/bmjopen-2020-048183. Full text in Research Archive Show summary

  Objectives: To assess detection rates for colorectal cancer (CRC) and advanced adenomas in asymptomatic CRC screening participants and bowel symptoms in association with CRC and advanced adenoma. Design: Cross-sectional study. Setting: Two screening centres. Participants: 42 554 men and women, aged 50-74 years, participating in a randomised CRC screening trial. 36 059 participants underwent a sigmoidoscopy (and follow-up colonoscopy if positive sigmoidoscopy) and 6495 underwent a colonoscopy after a positive faecal immunochemical test (FIT). Primary and secondary outcome measures: Proportion of asymptomatic participants diagnosed with CRC or advanced adenomas. Prevalence of bowel symptoms (rectal bleeding, change in bowel habits, diarrhoea, constipation, bloating, alternating bowel habits, general symptoms, other bowel symptoms) recorded by the endoscopist and their association with CRC and advanced adenomas. Results: Among sigmoidoscopy participants, 7336 (20.3%) reported at least one symptom. 120 (60%) out of 200 individuals with screen-detected CRC and 1301 (76.5%) out of 1700 with advanced adenoma were asymptomatic. Rectal bleeding was associated with detection of CRC and advanced adenoma (OR 4.3, 95% CI 3.1 to 6.1 and 1.8, 95% CI 1.5 to 2.1, respectively), while change in bowel habits only with CRC detection (OR 3.8, 95% CI 2.4 to 6.1). Among the FIT positives, 2173 (33.5%) reported at least one symptom. Out of 299 individuals with screen-detected CRC and 1639 with advanced adenoma, 167 (55.9%) and 1 175 (71.7%) were asymptomatic, respectively. Detection of CRC was associated with rectal bleeding (OR 1.8, 95% CI 1.4 to 2.3), change in bowel habits (OR 2.2, 95% CI 1.4 to 3.5) and abdominal pain (OR 1.8, 95% CI 1.2 to 2.7). Conclusions: Some bowel symptoms increased the likelihood of being diagnosed with CRC or advanced adenoma. However, the majority of individuals with these findings were asymptomatic. Asymptomatic individuals should be encouraged to participate in CRC screening.

• Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Bucher-Johannessen, Cecilie; Vinberg, Elina; Nordby, Jan Inge & Kangas, Harri [Show all 27 contributors for this article] (2021). The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants. BMC Cancer. 21. doi: 10.1186/s12885-021-08640-8. Full text in Research Archive Show summary

  Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.

• Knudsen, Markus Dines; Hoff, Geir; Tidemann-Andersen, Ida; Bodin, Gry Ekeberg; Øvervold, Sissel & Berstad, Paula (2020). Public Awareness and Perceptions of Colorectal Cancer Prevention: a Cross-Sectional Survey. Journal of Cancer Education. ISSN 0885-8195. doi: 10.1007/s13187-020-01721-5. Full text in Research Archive Show summary

  We aimed to investigate awareness of colorectal cancer (CRC) lifestyle risk factors, willingness to participate in CRC screening, and preferences concerning channels for information on CRC prevention in the general population, including the target age of the upcoming Norwegian national CRC screening program. The present study was a cross-sectional online survey of adults aged 39 to 55 years registered as Kantar Web Panel respondents in Norway. The survey included demographic characteristics, multiple choice knowledge questions of lifestyle risk factors for CRC, attitudes towards CRC screening, and preferred channels for receiving information on CRC prevention. Of 4375 participants invited, 2007 (46%) answered the survey. The average number of correctly identified lifestyle risk factors for CRC was 7.3 of ten. Women were significantly more likely than men, and those with university or college education more likely than those with lower education to correctly identify at least eight risk factors (odds ratio, OR = 1.53, 95% confidence interval, CI 1.25-1.87, and OR = 1.51, 95% CI 1.23-1.86, respectively). The number of correctly identified risk factors was positively associated with willingness to participate in CRC screening (P for trend < 0.001). The national public work force and the Norwegian Cancer Society were selected by 76% and 69% of the participants, respectively, to be trustworthy sources of information on CRC prevention. Awareness of CRC risk factors was associated with willingness to participate in CRC screening. The national public work force and Cancer Society can be generally accepted sources of CRC preventive information.

• Randel, Kristin Ranheim; Schult, Anna Lisa; Botteri, Edoardo; Hoff, Geir; Bretthauer, Michael & Ursin, Giske [Show all 20 contributors for this article] (2020). Colorectal cancer screening with repeated fecal immunochemical test versus sigmoidoscopy: baseline results from a randomized trial. Gastroenterology. ISSN 0016-5085. 160(4), p. 1085–1096. doi: 10.1053/j.gastro.2020.11.037. Full text in Research Archive Show summary

  Background and aims: The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown. Methods: Individuals aged 50-74 years living in South-East Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp ≥10 mm, ≥ three adenomas, any advanced adenomas, or CRC was found or subsequent to FIT > 15 μg hemoglobin/g feces. Data for this report were obtained after complete recruitment in both groups and included two full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (OR) were calculated. Results: We included 139,291 individuals; 69,195 randomized to sigmoidoscopy and 70,096 to FIT. Participation rate was 52% for sigmoidoscopy, 58% in the first FIT round and 68% for three cumulative FIT rounds. Compared to sigmoidoscopy, detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%, OR 0.92, 95% CI 0.75-1.13), but higher after three FIT rounds (0.49% vs 0.27%, OR 1.87, 95% CI 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy, 1.4% vs 2.4% (OR 0.57, 95% CI 0.53-0.62), but higher after three cumulative FIT rounds, 2.7% vs 2.4% (OR 1.14, 95% CI 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (p =.13). Conclusion: Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov (NCT01538550).

• Knudsen, Markus Dines; Botteri, Edoardo; Holme, Øyvind; Hjartåker, Anette; Song, Mingyang & Thiis-Evensen, Espen [Show all 11 contributors for this article] (2020). Association between lifestyle and site-specific advanced colorectal lesions in screening with faecal immunochemical test and sigmoidoscopy. Digestive and Liver Disease. ISSN 1590-8658. p. 1–7. doi: 10.1016/j.dld.2020.11.021. Full text in Research Archive Show summary

  Background: Lifestyle factors may help to identify individuals at high-risk for colorectal cancer (CRC). Aims: To examine the association between lifestyle, referral for follow-up colonoscopy and proximal neoplasia detection in CRC screening. Methods: In this observational study, 14,832 individuals aged 50-74 years were invited to faecal immunochemical test (FIT) or sigmoidoscopy screening. Advanced lesions (AL), including advanced adenomas, advanced serrated lesions and CRC were divided according to location: distal-only, or proximal with or without distal AL. We collected information on smoking habit, body mass index and alcohol intake through a questionnaire. Results: Out of 3,318 FIT and 2,988 sigmoidoscopy participants, 516 (16%) and 338 (11%), respectively, were referred for follow-up colonoscopy after a positive screening test. Two-hundred-and-fifty-six (4%) had distal-only and 119 (2%) proximal AL. In FIT participants, obesity and high alcohol intake were associated with proximal AL; odds ratio (95% confidence interval) 2.68 (1.36-5.26) and 2.16 (1.08-4.30), respectively. In sigmoidoscopy participants, current smoking was associated with proximal AL; 4.58 (2.24-9.38), and current smoking and obesity were associated with referral for colonoscopy; 2.80 (2.02-3.89) and 1.42 (1.01-2.00), respectively. Conclusion: Current smoking, obesity and high alcohol intake were associated with screen-detected proximal colorectal AL. Current smoking and obesity were associated with referral for follow-up colonoscopy in sigmoidoscopy screening.

• Pedersen, Ina Borgenheim; Bretthauer, Michael; Kalager, Mette; Løberg, Magnus; Hoff, Geir & Matapour, Senaria [Show all 13 contributors for this article] (2020). Incomplete endoscopic resection of colorectal polyps: a prospective quality assurance study. Endoscopy. ISSN 0013-726X. p. 1–9. doi: 10.1055/a-1243-0379. Full text in Research Archive
• Hoff, Geir; Ursin, Giske; Løberg, Magnus; Lange, Thomas de; Skovlund, Eva & Holme, Øyvind (2019). Continuous development of colorectal cancer screening programs. Acta Oncologica. ISSN 0284-186X. 3(1), p. 822–823. doi: 10.1080/0284186X.2019.1588475. Full text in Research Archive Show summary

  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.

• Randel, Kristin Ranheim; Botteri, Edoardo; Romstad, Katrine Maria Kauczynska; Frigstad, Svein Oskar; Bretthauer, Michael & Hoff, Geir [Show all 8 contributors for this article] (2019). Effects of Oral Anticoagulants and Aspirin on Performance of Fecal Immunochemical Tests in Colorectal Cancer Screening. Gastroenterology. ISSN 0016-5085. 156(6), p. 1642–1649.e1. doi: 10.1053/j.gastro.2019.01.040. Full text in Research Archive
• Hoff, Geir; Botteri, Edoardo; Høie, Ole Ingebreth; Garborg, Kjetil Kjeldstad; Wiig, Håvard & Huppertz-Hauss, Gert [Show all 9 contributors for this article] (2019). Polyp detection rates as quality indicator in clinical versus screening colonoscopy. Endoscopy International Open. 7(2). doi: 10.1055/a-0796-6477. Full text in Research Archive
• Joranger, Pål; Nesbakken, Arild; Sorbye, Halfdan; Hoff, Geir; Oshaug, Arne & Aas, Eline (2019). Survival and costs of colorectal cancer treatment and effects of changing treatment strategies: a model approach. European Journal of Health Economics. ISSN 1618-7598. p. 1–14. doi: 10.1007/s10198-019-01130-6. Full text in Research Archive Show summary

  New and emerging advances in colorectal cancer (CRC) treatment combined with limited healthcare resources highlight the need for detailed decision-analytic models to evaluate costs, survival and quality-adjusted life years. The objectives of this article were to estimate the expected lifetime treatment cost of CRC for an average 70-year-old patient and to test the applicability and flexibility of a model in predicting survival and costs of changing treatment scenarios. The analyses were based on a validated semi-Markov model using data from a Norwegian observational study (2049 CRC patients) to estimate transition probabilities and the proportion resected. In addition, inputs from the Norwegian Patient Registry, guidelines, literature, and expert opinions were used to estimate resource use. We found that the expected lifetime treatment cost for a 70-year-old CRC patient was €47,300 (CRC stage I €26,630, II €38,130, III €56,800, and IV €69,890). Altered use of palliative chemotherapy would increase the costs by up to 29%. A 5% point reduction in recurrence rate for stages I-III would reduce the costs by 5.3% and increase overall survival by 8.2 months. Given the Norwegian willingness to pay threshold per QALY gained, society's willingness to pay for interventions that could result in such a reduction was on average €28,540 per CRC patient. The life years gained by CRC treatment were 6.05 years. The overall CRC treatment costs appear to be low compared to the health gain, and the use of palliative chemotherapy can have a major impact on cost. The model was found to be flexible and applicable for estimating the cost and survival of several CRC treatment scenarios.

• Guldvog, Ivar; Reitsma, Laurens Cornelus; Johnsen, Lene Cathrin; Lauzike, Andromeda; Gibbs, Charlotte Christine & Carlsen, Eivind [Show all 13 contributors for this article] (2019). Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial. Annals of Internal Medicine. ISSN 0003-4819. 170(7), p. 453–464. doi: 10.7326/M18-0284. Full text in Research Archive Show summary

  Background: Hashimoto disease is a chronic autoimmune thyroiditis. Despite adequate hormone substitution, some patients have persistent symptoms that may be the result of immunologic pathophysiology. Objective: To determine whether thyroidectomy improves symptoms in patients with Hashimoto thyroiditis who still have symptoms despite having normal thyroid gland function while receiving medical therapy. Design: Randomized trial. (ClinicalTrials.gov: NCT02319538) Setting: Secondary care hospital in Norway. Patients: 150 patients aged 18 to 79 years with persistent Hashimoto-related symptoms despite euthyroid status while receiving hormone replacement therapy and with serum antithyroid peroxidase (anti-TPO) antibody titers greater than 1000 IU/mL. Intervention: Total thyroidectomy or medical management with hormone substitution to secure euthyroid status in both groups. Measurements: The primary outcome was general health score on the Short Form-36 Health Survey (SF-36) at 18 months. Secondary outcomes were adverse effects of surgery, the other 7 SF-36 subscores, fatigue questionnaire scores, and serum anti-TPO antibody titers at 6, 12, and 18 months. Results: During follow-up, only the surgical group demonstrated improvement: Mean general health score increased from 38 to 64 points, for a between-group difference of 29 points (95% CI, 22 to 35 points) at 18 months. Fatigue score decreased from 23 to 14 points, for a between-group difference of 9.3 points (CI, 7.4 to 11.2 points). Chronic fatigue frequency decreased from 82% to 35%, for a between-group difference of 39 percentage points (CI, 23 to 53 percentage points). Median serum anti-TPO antibody titers decreased from 2232 to 152 IU/mL, for a between-group difference of 1148 IU/mL (CI, 1080 to 1304 IU/mL). In multivariable regression analyses, the adjusted treatment effects remained similar to the unadjusted effects. Limitation: Results are applicable only to a subgroup of patients with Hashimoto disease, and follow-up was limited to 18 months. Conclusion: Total thyroidectomy improved health-related quality of life and fatigue, whereas medical therapy did not. This improvement, along with concomitant elimination of serum anti-TPO antibodies, may elucidate disease mechanisms.

• Hoff, Geir; Lange, Thomas de; Bretthauer, Michael; Dahler, Stein; Halvorsen, Fred-Arne & Huppertz-Hauss, Gert [Show all 12 contributors for this article] (2019). Registration bias in a clinical quality register. Endoscopy International Open. 7(1), p. E90–E98. doi: 10.1055/a-0806-7006. Full text in Research Archive Show summary

  Background and aims:The quality of medical quality registers is poorly defined and lack of trust in data due to low completeness may be a major barrier against their use in quality improvement interventions. The aim of the current observational study was to explore how selective reporting may influence adverse events registered in the Norwegian quality register for colonoscopy (Gastronet). Materials and Methods:Gastronet's database includes data provided by endoscopists, nurses and patients. All outpatient colonoscopies reported to Gastronet in 2015 were included and compared to the total number of colonoscopies performed in Norway as retrieved from the National Patient Registry. Hospitals were categorized into four groups according to reporting completeness < 50 %, 50 % to 69 %, 70 % to 89 % and ≥ 90 %. The number of recorded adverse events (AEs) and procedure time were analyzed. Multivariate logistic regression models were fitted to explore independent factors for selection bias. Results: A total of 22,364 colonoscopies were reported to the National Patient Register of which 15,855 (71 %) were registered in Gastronet. Feedback was received from 11,079 patients (50 %). The frequency of AEs increased from 0.6 % in completeness group < 50 % to 1.6 % in completeness group ≥ 90 % ( P  < 0.001). Long colonoscopy procedure time was associated with low reporting completeness. Patient feedback was associated with older age, cecal intubation success and sedation-free colonoscopy. Conclusion:Incomplete registration in a colonoscopy quality register is associated with underreporting of AEs. Longer procedure time, a surrogate marker for time constraint, is associated with low completeness.

• Bugajski, M; Wieszczy, P; Rupinski, M; Hoff, Geir; Huppertz-Hauss, Gert & Regula, J [Show all 8 contributors for this article] (2019). Effectiveness of digital feedback on patient experience and 30-day complications after screening colonoscopy: a randomized Health services study. Endoscopy International Open. 7(4), p. E537–E544. doi: 10.1055/a-0830-4648. Full text in Research Archive
• Rounge, Trine Ballestad; Meisal, Roger; Nordby, Jan Inge; Ambur, Ole Herman; Lange, Thomas de & Hoff, Geir (2018). Evaluating gut microbiota profiles from archived fecal samples. BMC Gastroenterology. 18(171). doi: 10.1186/s12876-018-0896-6. Full text in Research Archive Show summary

  Background Associations between colorectal cancer and microbiota have been identified. Archived fecal samples might be valuable sample sources for investigating causality in carcinogenesis and biomarkers discovery due to the potential of performing longitudinal studies. However, the quality, quantity and stability of the gut microbiota in these fecal samples must be assessed prior to such studies. We evaluated i) cross-contamination during analysis for fecal blood and ii) evaporation in stored perforated fecal immunochemical tests (iFOBT) samples, iii) temperature stability as well as iv) comparison of the gut microbiota diversity and composition in archived, iFOBT and fresh fecal samples in order to assess feasibility of large scale microbiota studies. Methods The microbiota profiles were obtained by sequencing the V3-V4 region of 16S rDNA gene. Results The iFOBT does not introduce any cross-sample contamination detectable by qPCR. Neither could we detect evaporation during freeze-thaw cycle of perforated iFOBT samples. Our results confirm room temperature stability of the gut microbiome. Diverse microbial profiles were achieved in 100% of fresh, 81% of long-term archived and 96% of iFOBT samples. Microbial diversity and composition were comparable between fresh and iFOBT samples, however, diversity differed significantly between long-term archived, fresh and iFOBT samples. Conclusion Our data showed that it is feasible to exploit archived fecal sample sets originally collected for testing of fecal blood. The advantages of using these sample sets for microbial biomarker discovery and longitudinal observational studies are the availability of high-quality diagnostic and follow-up data. However, care must be taken when microbiota are profiled in long-term archived fecal samples.

• Knudsen, Markus Dines; Hjartåker, Anette; Robb, Kathryn A.; Lange, Thomas de; Hoff, Geir & Berstad, Paula Marianna (2018). Improving Cancer Preventive Behaviors: A Randomized Trial of Tailored Lifestyle Feedback in Colorectal Cancer Screening. Cancer Epidemiology, Biomarkers and Prevention. ISSN 1055-9965. 27(12), p. 1442–1449. doi: 10.1158/1055-9965.EPI-18-0268. Full text in Research Archive Show summary

  Background: Cancer screening provides an opportunity to increase awareness of cancer-preventive lifestyle behaviors such as nonsmoking, physical activity, low alcohol consumption, and a healthy diet. We tested the effect of standardized, individually tailored written feedback (TF), and a standard leaflet (SL) on 1-year lifestyle behaviors in a colorectal cancer screening setting. Methods: A total of 3,642 men and women aged 50–74 years invited to sigmoidoscopy screening were randomly assigned to: (i) TF; (ii) SL for cancer-preventive lifestyle behaviors; or (iii) control. Participants were mailed two self-reported lifestyle questionnaires (LSQ) 1 year apart. The TF intervention was based on the prescreening LSQ answers. We analyzed differences [with 95% confidence intervals (CI)] by comparing prescreening to 1-year follow-up of single cancer-preventive factors and the number of cancer-preventive lifestyle behaviors (range 0–4) between the groups by multivariable logistic regression and analysis of covariance (ANCOVA). Results: A total of 1,054 screening participants without neoplastic findings (29% of those invited to screening) were included in this study. Participants in the TF group increased their number of cancer-preventive lifestyle behaviors significantly compared with those in the control group by 0.11 (95% CI, 0.02 to 0.19). Overweight/obese individuals in the TF group had a −0.84 kg (95% CI, −1.47 to −0.22) larger reduction in body weight compared with the control group. Conclusions: TF at sigmoidoscopy screening led to small improvements in cancer-preventive behaviors.

• Holme, Øyvind; Pedersen, Ina Borgenheim; Medhus, Asle Wilhelm; Aabakken, Lars; Glomsaker, Tom Birger & Kvamme, Jan-Magnus [Show all 14 contributors for this article] (2018). Endoscopy assistants influence the quality of colonoscopy. Endoscopy. ISSN 0013-726X. 50(9), p. 871–877. doi: 10.1055/s-0044-101706. Full text in Research Archive Show summary

  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. © 2018 Georg Thieme Verlag KG Stuttgart

• Holme, Øyvind; Løberg, Magnus; Kalager, Mette; Bretthauer, Michael; Hernán, Miguel A. & Aas, Eline [Show all 14 contributors for this article] (2018). Long-term effectiveness of sigmoidoscopy screening on colorectal cancer incidence and mortality in women and men: A randomized trial. Annals of Internal Medicine. ISSN 0003-4819. 168(11), p. 775–782. doi: 10.7326/M17-1441. Full text in Research Archive Show summary

  Background: The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear. Objective: To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT00119912) Setting: Oslo and Telemark County, Norway. Participants: Adults aged 50 to 64 years at baseline without prior CRC. Intervention: 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. Measurements: Age-adjusted CRC incidence and mortality stratified by sex. Results: 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). Limitation: Follow-up through national registries. Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women.

• Jodal, Henriette Cecilie; Løberg, Magnus; Holme, Øyvind; Adami, Hans Olov; Bretthauer, Michael & Emilsson, Louise [Show all 9 contributors for this article] (2018). Mortality from post-screening (interval) colorectal cancers is comparable to that from cancer in unscreened patients-a randomized sigmoidoscopy trial. Gastroenterology. ISSN 0016-5085. 155(6), p. 1787–1794. doi: 10.1053/j.gastro.2018.08.035. Full text in Research Archive
• Pinsky, Paul F.; Løberg, Magnus; Senore, Carlo; Wooldrage, Kate; Atkin, Wendy S. & Bretthauer, Michael [Show all 12 contributors for this article] (2018). Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening. Gastroenterology. ISSN 0016-5085. 155(4), p. 1059–1068. doi: 10.1053/j.gastro.2018.06.040. Full text in Research Archive
• Pedersen, Ina Borgenheim; Løberg, Magnus; Hoff, Geir; Kalager, Mette; Bretthauer, Michael & Holme, Øyvind (2018). Polypectomy techniques among gastroenterologists in Norway – a nationwide survey. Endoscopy International Open. 6(7). doi: 10.1055/a-0607-0727. Full text in Research Archive Show summary

  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.

• Knudsen, Markus Dines; Hjartåker, Anette; Olsen, Marie Kristin Ek; Hoff, Geir; Lange, Thomas de & Bernklev, Tomm [Show all 7 contributors for this article] (2018). Changes in health behavior 1 year after testing negative at a colorectal cancer screening: a randomized-controlled study. European Journal of Cancer Prevention. ISSN 0959-8278. 27(4), p. 316–322. doi: 10.1097/CEJ.0000000000000328. Full text in Research Archive
• Kirkøen, Benedicte; Berstad, Paula Marianna; Botteri, Edoardo; Dalén, Eirin; Nilsen, Jens Aksel & Hoff, Geir [Show all 8 contributors for this article] (2017). Acceptability of two colorectal cancer screening tests: pain as a key determinant in sigmoidoscopy. Endoscopy. ISSN 0013-726X. 49(11), p. 1075–1086. doi: 10.1055/s-0043-117400. Full text in Research Archive
• Knudsen, Markus Dines; Berstad, Paula Marianna; Hjartåker, Anette; Gulichsen, Elisabeth Haagensen; Hoff, Geir & Lange, Thomas de [Show all 8 contributors for this article] (2017). Lifestyle predictors for non-participation and outcome in the second round of faecal immunochemical test in colorectal cancer screening. British Journal of Cancer. ISSN 0007-0920. 117(4), p. 461–469. doi: 10.1038/bjc.2017.189. Full text in Research Archive Show summary

  Background: To reduce colorectal cancer (CRC) mortality through population-based screening programmes using faecal tests, it is important that individuals continue to participate in the repeated rounds of screening. We aimed to identify lifestyle predictors for discontinuation of faecal immunochemical test (FIT) screening after the first round, as well as lifestyle predictors for colorectal neoplasia detected in the second-round FIT screening. Methods: In this longitudinal study, we invited 6959 individuals aged 50–74 years from south-east Norway for a first round of FIT screening and to complete a self-reported lifestyle questionnaire on demographic factors, body mass index (BMI, kg m−2), smoking habits, physical activity, consumption of alcohol and dietary items. Two years later, we estimated the associations between these factors, non-participation and screening results in the second round of FIT screening using adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of the 3114 responders to the questionnaire who completed the first-round FIT and who were invited to participate in second-round FIT screening, 540 (17%) did not participate. The OR and (95% CI) for discontinuation of FIT screening after the first round was 1.61 (1.24–2.10) for current smoking compared with non-smoking; 2.01 (1.25–3.24) for BMI ≥ 35 kg m−2 compared with BMI 16.9–24.9 kg m−2 and 0.70 (0.52–0.94) for physical activity in the third quartile vs the first. Among participants, smoking, high BMI and high alcohol consumption were associated with an increased odds of detecting colorectal neoplasia (n=107). Conclusions: These results may indicate that Norwegian FIT screening participants who discontinue after the first round have lifestyle behaviours associated with increased risk of CRC.

• Lange, Thomas de; Randel, Kristin Ranheim; Schult, Anna Lisa; Knudsen, Markus Dines; Kirkøen, Benedicte & Botteri, Edoardo [Show all 11 contributors for this article] (2017). Sigmoidoskopi og testing for blod i avføringen - En sammenlignende screeningstudie. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 137(10), p. 727–730. doi: 10.4045/tidsskr.16.1031. Full text in Research Archive
• Bugajski, Marek; Wieszczy, Paulina; Hoff, Geir; Rupinski, Maciej; Regula, Jaroslaw & Kaminski, Michal Filip (2017). Modifiable factors associated with patient-reported pain during and after screening colonoscopy. Gut. ISSN 0017-5749. 67(11), p. 1958–1964. doi: 10.1136/gutjnl-2017-313905. Full text in Research Archive
• Hoff, Geir; Lange, Thomas de; Bretthauer, Michael; Buset, Magne; Dahler, Stein & Halvorsen, Fred-Arne [Show all 15 contributors for this article] (2017). Patient-reported adverse events after colonoscopy in Norway. Endoscopy. ISSN 0013-726X. 49(8), p. 745–753. doi: 10.1055/s-0043-105265. Full text in Research Archive
• Holme, Øyvind; Schoen, Robert E.; Senore, Carlo; Segnan, Nereo; Hoff, Geir & Løberg, Magnus [Show all 9 contributors for this article] (2017). Effectiveness of flexible sigmoidoscopy screening in men and women and different age groups: Pooled analysis of randomised trials. The BMJ. 356. doi: 10.1136/bmj.i6673. Full text in Research Archive Show summary

  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.

• Kaminski, Michal Filip; Thomas-Gibson, Siwan; Bugajski, Marek; Bretthauer, Michael; Rees, Colin J. & Dekker, Evelien [Show all 29 contributors for this article] (2017). Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy. ISSN 0013-726X. 49(4), p. 378–397. doi: 10.1055/s-0043-103411. Full text in Research Archive
• Huppertz-Hauss, Gert; Høivik, Marte; Jelsness-Jørgensen, Lars-Petter; Opheim, Randi; Henriksen, Magne & Høie, Ole Ingebreth [Show all 13 contributors for this article] (2017). Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 52(3), p. 351–358. doi: 10.1080/00365521.2016.1256425. Full text in Research Archive
• Hoff, Geir; Holme, Øyvind; Bretthauer, Michael; Sandvei, Per; Darre-Næss, Ole & Stallemo, Asbjørn [Show all 11 contributors for this article] (2017). Cecum intubation rate as quality indicator in clinical versus screening colonoscopy. Endoscopy International Open. 5(6), p. E489–E495. doi: 10.1055/s-0043-106180. Full text in Research Archive Show summary

  Background and study aims: Some guidelines recommend a minimum standard of 90 % cecal intubation rate (CIR) in routine clinics and 95 % in screening colonoscopy, while others have not made this distinction – both with limited evidence to support either view. This study questions the rationale for making such differentiation. Patients and methods: We assessed cecum intubation rates amongst colonoscopies recorded in the Norwegian national quality register Gastronet by 35 endoscopists performing both clinical and screening colonoscopies. Colonoscopies were categorized into primary screening colonoscopy, work-up colonoscopy of screen-positives and clinical colonoscopy or surveillance. Cases with insufficient bowel preparation or mechanical obstruction were excluded. Endoscopists were categorized into “junior” and “senior” endoscopists depending on training and experience. Univariable and multivariable logistic regression analyses were applied. Results: During a 2-year period, 10,267 colonoscopies were included (primary screening colonoscopy: 746; work-up colonoscopy of screen-positives: 2,604; clinical colonoscopy or surveillance: 6917). The crude CIR in clinical routine colonoscopy, primary screening colonoscopy and work-up colonoscopy was 97.1 %, 97.1 % and 98.6 %, respectively. In a multiple logistic regression analysis, there were no differences in CIR between the 3 groups. Poor bowel cleansing and female sex were independent predictors for intubation failure. Conclusion: Cecal intubation rate in clinical colonoscopies and colonoscopy screening are similar. There is no reason to differentiate between screening and clinical colonoscopy with regard to CIR.

• Kaminski, Michal Filip; Thomas-Gibson, Siwan; Bugajski, Marek; Bretthauer, Michael; Rees, Colin J. & Dekker, Evelien [Show all 29 contributors for this article] (2017). Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 5(3), p. 309–334. doi: 10.1177/2050640617700014. Full text in Research Archive
• Aas, Eline; Iversen, Tor & Hoff, Geir (2017). The effect of education on health behavior after screening for colorectal cancer. In Bolin, Kristian (Eds.), Human Capital and Health Behavior. Advances in Health Economics and Health Services Research. Emerald Group Publishing Limited. ISSN 9781786354662. p. 207–242. doi: 10.1108/S0731-219920170000025007. Full text in Research Archive Show summary

  Misinterpretation of a negative test results in health screening may initiate less preventive effort and more future lifestyle-related disease. We predict that misinterpretation occurs more frequently among individuals with a low level of education compared with individuals with a high level of education. The empirical analyses are based on unique data from a randomized controlled screening experiment in Norway, NORCCAP (NORwegian Colorectal Cancer Prevention). The dataset consists of approximately 50,000 individuals, of whom 21,000 were invited to participate in a once only screening with sigmoidoscopy. For all individuals, we also have information on outpatient consultations and inpatient stays and education. The result of health behaviour is mainly measured by lifestyle-related diseases, such as COPD, hypertension and diabetes type 2, identified by ICD-10 codes. The results according to intention-to-treat indicate that screening does not increase the occurrence of lifestyle related diseases among individuals with a high level of education, while there is an increase for individuals with low levels of education. These results are supported by the further analyses among individuals with a negative screening test.

• Bretthauer, Michael; Kaminski, Michal Filip; Løberg, Magnus; Zauber, Ann G.; Regula, Jaroslaw & Kuipers, Ernst J. [Show all 20 contributors for this article] (2016). Population-Based colonoscopy screening for colorectal cancer : A randomized clinical trial. JAMA Internal Medicine. ISSN 2168-6106. 176(7), p. 894–902. doi: 10.1001/jamainternmed.2016.0960. Full text in Research Archive
• Holme, Øyvind; Lange, Thomas de; Stallemo, Asbjørn; Wiig, Håvard; Hasund, Audun & Dvergsnes, Katrine [Show all 12 contributors for this article] (2016). Routine vs. on-demand analgesia in colonoscopy: a randomized clinical trial. Endoscopy. ISSN 0013-726X. 48(09), p. 823–828. doi: 10.1055/s-0042-108433. Full text in Research Archive
• Knudsen, Markus Dines; Lange, Thomas de; Botteri, Edoardo; Nguyen, Dung-Hong; Evensen, Helge & Steen, Chloe Beate [Show all 10 contributors for this article] (2016). Favorable lifestyle before diagnosis associated with lower risk of screen-detected advanced colorectal neoplasia. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 22(27), p. 6276–6286. doi: 10.3748/wjg.v22.i27.6276. Full text in Research Archive
• Jover, Rodrigo; Bretthauer, Michael; Dekker, Evelien; Holme, Øyvind; Kaminski, Michal Filip & Løberg, Magnus [Show all 22 contributors for this article] (2016). Rationale and design of the European Polyp Surveillance (EPoS) trials. Endoscopy. ISSN 0013-726X. 48(6), p. 571–578. doi: 10.1055/s-0042-104116. Full text in Research Archive
• Kirkøen, Benedicte; Berstad, Paula Marianna; Botteri, Edoardo; Bernklev, Linn; El-Safadi, Badboni & Hoff, Geir [Show all 8 contributors for this article] (2016). Psychological effects of colorectal cancer screening: Participants vs individuals not invited. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 22(43), p. 9631–9641. doi: 10.3748/wjg.v22.i43.9631. Full text in Research Archive
• Young, Graeme P.; Senore, Carlo; Mandel, Jack S.; Allison, James E.; Atkin, Wendy S. & Benamouzig, Robert [Show all 26 contributors for this article] (2016). Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer. Cancer. ISSN 0008-543X. 122(6), p. 826–839. doi: 10.1002/cncr.29865. Full text in Research Archive
• Huppertz-Hauss, Gert; Høivik, Marte; Jelsness-Jørgensen, Lars-Petter; Henriksen, Magne; Høie, Ole Ingebreth & Jahnsen, Jørgen [Show all 9 contributors for this article] (2016). Health-related quality of life in patients with inflammatory bowel disease 20 years after diagnosis: results from the IBSEN study. Inflammatory Bowel Diseases. ISSN 1078-0998. 22(7), p. 1679–1687. doi: 10.1097/MIB.0000000000000806. Full text in Research Archive
• Moritz, Volker; Holme, Øyvind; LeBlanc, Marissa & Hoff, Geir (2016). An explorative study from the Norwegian Quality Register Gastronet comparing self-estimated versus registered quality in colonoscopy performance. Endoscopy International Open. 4(3), p. E326–332. doi: 10.1055/s-0042-100904. Full text in Research Archive
• Berstad, Paula Marianna; Botteri, Edoardo; Larsen, Inger Kristin; Løberg, Magnus; Kalager, Mette & Holme, Øyvind [Show all 8 contributors for this article] (2016). Lifestyle changes at middle age and mortality: A population-based prospective cohort study. Journal of Epidemiology and Community Health. ISSN 0143-005X. 71(1), p. 59–66. doi: 10.1136/jech-2015-206760. Full text in Research Archive
• Lorentzen, Jon Andreas; Grzyb, Krzysztof; Angelis, Paula De; Hoff, Geir; Eide, Tor Jacob & Andresen, Per Arne (2016). Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study. Clinical medicine insights. Pathology. 9(1), p. 19–28. doi: 10.4137/CPath.s40143. Full text in Research Archive
• Kirkøen, Benedicte; Berstad, Paula Marianna; Botteri, Edoardo; Åvitsland, Tone Lise; Ossum, Alvilde Maria & Lange, Thomas de [Show all 8 contributors for this article] (2016). Do no harm: No psychological harm from colorectal cancer screening. British Journal of Cancer. ISSN 0007-0920. 114(5), p. 497–504. doi: 10.1038/bjc.2016.14. Full text in Research Archive
• Huppertz-Hauss, Gert; Aas, Eline; Høivik, Marte; Langholz, Ebbe; Odes, Selwyn & Småstuen, Milada C [Show all 10 contributors for this article] (2016). Comparison of the Multiattribute Utility Instruments EQ-5D and SF-6D in a Europe-Wide Population-Based Cohort of Patients with Inflammatory Bowel Disease 10 Years after Diagnosis. Gastroenterology Research and Practice. ISSN 1687-6121. 2016:5023973, p. 1–9. doi: 10.1155/2016/5023973. Full text in Research Archive
• Moritz, Volker; Bretthauer, Michael; Holme, Øyvind; Fagerland, Morten; Løberg, Magnus & Glomsaker, Tom Birger [Show all 10 contributors for this article] (2016). Time trends in quality indicators of colonoscopy. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 4(1), p. 110–120. doi: 10.1177/2050640615570147. Full text in Research Archive
• Huppertz-Hauss, Gert; Høivik, Marte; Langholz, E; Odes, Selwyn; Småstuen, Milada Cvancarova & Stockbrügger, Reinhold [Show all 9 contributors for this article] (2015). Health-related Quality of Life in Inflammatory Bowel Disease in a European-wide Population-based Cohort 10 Years After Diagnosis. Inflammatory Bowel Diseases. ISSN 1078-0998. 21(2), p. 337–344. doi: 10.1097/MIB.0000000000000272. Full text in Research Archive
• Huitfeldt, Anders; Kalager, Mette; Robins, James; Hoff, Geir & Hernan, Miguel A. (2015). Methods to Estimate the Comparative Effectiveness of Clinical Strategies that Administer the Same Intervention at Different Times. Current Epidemiology Reports. ISSN 2196-2995. 2(3), p. 149–161. doi: 10.1007/s40471-015-0045-5. Full text in Research Archive
• Hoff, Geir (2015). Look to Poland! Conversion from opportunistic screening to a randomized, national screening program for colorectal cancer. Endoscopy. ISSN 0013-726X. 47(12), p. 1104–1105. doi: 10.1055/s-0034-1393430. Full text in Research Archive
• Swanson, Sonja; Holme, Øyvind; Løberg, Magnus; Kalager, Mette; Bretthauer, Michael & Hoff, Geir [Show all 8 contributors for this article] (2015). Bounding the per-protocol effect in randomized trials: an application to colorectal cancer screening. Trials. 16(541). doi: 10.1186/s13063-015-1056-8. Full text in Research Archive Show summary

  Background The per-protocol effect is the effect that would have been observed in a randomized trial had everybody followed the protocol. Though obtaining a valid point estimate for the per-protocol effect requires assumptions that are unverifiable and often implausible, lower and upper bounds for the per-protocol effect may be estimated under more plausible assumptions. Strategies for obtaining bounds, known as “partial identification” methods, are especially promising in randomized trials. Results We estimated bounds for the per-protocol effect of colorectal cancer screening in the Norwegian Colorectal Cancer Prevention trial, a randomized trial of one-time sigmoidoscopy screening in 98,792 men and women aged 50–64 years. The screening was not available to the control arm, while approximately two thirds of individuals in the treatment arm attended the screening. Study outcomes included colorectal cancer incidence and mortality over 10 years of follow-up. Without any assumptions, the data alone provide little information about the size of the effect. Under the assumption that randomization had no effect on the outcome except through screening, a point estimate for the risk under no screening and bounds for the risk under screening are achievable. Thus, the 10-year risk difference for colorectal cancer was estimated to be at least −0.6 % but less than 37.0 %. Bounds for the risk difference for colorectal cancer mortality (–0.2 to 37.4 %) and all-cause mortality (–5.1 to 32.6 %) had similar widths. These bounds appear helpful in quantifying the maximum possible effectiveness, but cannot rule out harm. By making further assumptions about the effect in the subpopulation who would not attend screening regardless of their randomization arm, narrower bounds can be achieved. Conclusions Bounding the per-protocol effect under several sets of assumptions illuminates our reliance on unverifiable assumptions, highlights the range of effect sizes we are most confident in, and can sometimes demonstrate whether to expect certain subpopulations to receive more benefit or harm than others. Trial registration Clinicaltrials.gov identifier NCT00119912 (registered 6 July 2005)

• Joranger, Pål; Nesbakken, Arild; Hoff, Geir; Sorbye, Halfdan; Oshaug, Arne & Aas, Eline (2015). Modeling and Validating the Cost and Clinical Pathway of Colorectal Cancer. Medical decision making. ISSN 0272-989X. 35(2), p. 255–265. doi: 10.1177/0272989X14544749. Full text in Research Archive

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• Berstad, Paula; Schult, Anna Lisa; Hoff, Geir Svein; Ursin, Giske & Randel, Kristin Ranheim (2023). Sosiale forskjeller i forprosjektet for tarmkreftscreening. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(5). doi: 10.4045/tidsskr.22.0760. Full text in Research Archive
• Hoff, Geir; Botteri, Edoardo; Berstad, Paula & Randel, Kristin Ranheim (2022). Norway – a retarded country close to 20 years since EU recommended colorectal cancer screening? A failure or a success? Norsk Epidemiologi. ISSN 0803-2491. 30(1-2), p. 83–86. doi: 10.5324/nje.v30i1-2.4982. Full text in Research Archive
• Birkeland, Einar Elvbakken; Kværner, Ane Sørlie; Istvan, Paula; Bermanian, Vahid; Bucher-Johannessen, Cecilie & Avershina, Ekaterina [Show all 9 contributors for this article] (2022). The microbiome in fecal immunochemical tests from colorectal cancer screening participants – can it be used as a screening biomarker? Full text in Research Archive
• Avershina, Ekaterina; Birkeland, Einar Elvbakken; Berstad, Paula; Hoff, Geir Svein & Rounge, Trine Ballestad (2022). Total neoplastic polyp volume is correlated to several bacterial taxa in faecal immunochemical test-positive CRC-screening participants. Full text in Research Archive
• Avershina, Ekaterina; Birkeland, Einar Elvbakken; Berstad, Paula; Hoff, Geir Svein & Rounge, Trine Ballestad (2022). Total neoplastic polyp volume is correlated to several bacterial taxa in faecal immunochemical test-positive CRC-screening participants. Full text in Research Archive
• Hoff, Geir (2021). Quality assurance in colonoscopy: Is case mix a problem? Endoscopy. ISSN 0013-726X. doi: 10.1055/a-1690-6488. Full text in Research Archive
• Kværner, Ane Sørlie; Knudsen, Markus Dines; Hjartåker, Anette; Henriksen, Hege; Blomhoff, Rune & Hoff, Geir Svein [Show all 9 contributors for this article] (2021). Kost, livsstil og tarmscreening. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. Full text in Research Archive
• Løberg, Magnus; Kalager, Mette & Hoff, Geir (2018). Tailoring the message with selective reporting. European Journal of Epidemiology (EJE). ISSN 0393-2990. doi: 10.1007/s10654-018-0416-6. Full text in Research Archive
• Holme, Øyvind; Løberg, Magnus Bjørson; Kalager, Mette; Bretthauer, Michael & Hoff, Geir (2018). In response. Annals of Internal Medicine. ISSN 0003-4819. 169(9), p. 663–664. doi: 10.7326/L18-0512. Full text in Research Archive
• Hoff, Geir; Lange, Thomas de & Ursin, Giske (2017). Optimalisering gjennom randomisering. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 137(20), p. 1578–1578. doi: 10.4045/tidsskr.17.0876. Full text in Research Archive
• Bretthauer, Michael; Kaminski, Michal Filip; Hassan, Cecare; Kalager, Mette; Holme, Øyvind & Hoff, Geir [Show all 10 contributors for this article] (2016). America, We Are Confused: The Updated U.S. Preventive Services Task Force Recommendation on Colorectal Cancer Screening. Annals of Internal Medicine. ISSN 0003-4819. 166(2), p. 139–140. doi: 10.7326/M16-1805. Full text in Research Archive
• Jodal, Henriette Cecilie; Løberg, Magnus; Adami, Hans Olov; Bretthauer, Michael; Hoff, Geir & Kalager, Mette (2016). Interval Colorectal Cancers after Screening - More Aggressive than Clinical Cancers? Full text in Research Archive
• Holme, Øyvind; Hoff, Geir & Løberg, Magnus (2016). Colorectal cancer screening. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 316(16), p. 1714–1714. doi: 10.1001/jama.2016.13846. Full text in Research Archive
• Bretthauer, Michael; Kalager, Mette; Adami, Hans Olov & Hoff, Geir (2016). Who Is for CO2? Slow Adoption of Carbon Dioxide Insufflation in Colonoscopy. Annals of Internal Medicine. ISSN 0003-4819. 165(2), p. 145–6. doi: 10.7326/M16-0209. Full text in Research Archive

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