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.

OBJECTIVE: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.

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.

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 verified for Phascolarctobacterium succinatutens and negative associations were shown for Phascolarctobacterium faecium and adenoma in curatedMetagenomicData. Men show a higher prevalence of P. succinatutens across cohorts. Co-occurrence among Phascolarctobacterium species was low (<6%). Each of the three species shows distinct microbial composition and forms distinct correlation networks with other bacterial taxa, although Dialister invisus was negatively correlated to all investigated Phascolarctobacterium species. Pangenome analyses showed P. succinatutens to be enriched for genes related to porphyrin metabolism and degradation of complex carbohydrates, whereas glycoside hydrolase enzyme 3 was specific to P. faecium.IMPORTANCEUntil now Phascolarctobacterium has been going under the radar as a CRC-associated genus despite having been noted, but overseen, as such for over a decade. We found not just one, but two species of Phascolarctobacterium to be associated with CRC-Phascolarctobacterium succinatutens was more abundant in adenoma/CRC, while Phascolarctobacterium faecium was less abundant in adenoma. Each of them represents distinct communities, constituted by specific microbial partners and metabolic capacities-and they rarely occur together in the same patients. We have verified that P. succinatutens is increased in adenoma and CRC and this species should be recognized among the most important CRC-associated bacteria.

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 estimated assuming that the efficacy of colonoscopy in the proximal colon was similar to that observed in the distal colon in the sigmoidoscopy screening trials. The simulation model was validated using data from Norwegian participants in a colonoscopy screening trial. Results This analysis included 358 204 individuals (181 971 women [51%]) aged 55 to 64 years at inclusion with a median follow-up time ranging from 15 to 17 years. Compared with usual care, colonoscopy prevented an estimated 50 (95% CI, 42-58) CRC cases per 100 000 person-years, corresponding to 30% incidence reduction (rate ratio, 0.70 [95% CI, 0.66-0.75]), and prevented an estimated 15 (95% CI, 11-19) CRC deaths per 100 000 person-years, corresponding to 32% mortality reduction (rate ratio, 0.68 [95% CI, 0.61-0.76]). The additional benefit of colonoscopy screening compared with sigmoidoscopy was 12 (95% CI, 10-14) fewer CRC cases and 4 (95% CI, 3-5) fewer CRC deaths per 100 000 person-years, corresponding to percentage point reductions of 6.9 (95% CI, 6.0-7.9) for CRC incidence and 7.6 (95% CI, 5.7-9.6) for CRC mortality. The number needed to switch from sigmoidoscopy to colonoscopy screening was 560 (95% CI, 486-661) to prevent 1 CRC case and 1611 (95% CI, 1275-2188) to prevent 1 CRC death. Conclusions and Relevance The findings of this comparative effectiveness study assessing long-term follow-up after CRC screening suggest that there was an additional preventive effect on CRC incidence and mortality associated with colonoscopy screening compared with sigmoidoscopy screening, but the additional preventive effect was less than what was achieved by introducing sigmoidoscopy screening where no screening existed. The results probably represent the upper limit of what may be achieved with colonoscopy screening compared with sigmoidoscopy screening.

INTRODUCTION: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 or older 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. In addition, we calculated the number of CRC 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 ratio [HR] 0.87, 95% confidence interval [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; P heterogeneity = 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 ( P trend < 0.001). For past use, HR 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 ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period. DISCUSSION:In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

Background and study aimsLong-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 methodsIndividuals 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.Results35,710 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%. Compared to participants with excellent bowel cleansing, those with poor bowel cleansing had an odds ratio for adenoma detection of 0.66 (95% confidence interval 0.55-0.79). We found substantial differences in the assessment of bowel cleansing quality among endoscopists.ConclusionsInadequate bowel cleansing reduces the efficacy of sigmoidoscopy screening, by lowering ADR. A validated rating scale and improved bowel preparation are needed to make sigmoidoscopy an appropriate screening method.Trial registration Clinicaltrials.gov (NCT 01538550)

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 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively. CONCLUSIONS:Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events. TRIAL REGISTRATION:Clinicaltrials.gov identifier: NCT01538550.

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.

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

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 most frequent adverse events were lower gastrointestinal bleeding (0.86%), abdominal pain (0.48%), vasovagal reaction (0.39%), postpolypectomy syndrome (0.20%), and perforation (0.08%). 23 (0.22%) individuals had non-gastrointestinal adverse events. Risk factors associated with adverse events were older age, female sex, screening centre, anticoagulant therapy, number of polypectomies, size of lesion removed, presence of proximal lesion, and adenocarcinoma. Adverse event rates per endoscopist ranged from 0% to 4.9%.Conclusion Adverse events after colonoscopy of screening positives occurred in about 2 out of 100 procedures. Three-quarters of events were mild. Awareness of risk factors may help endoscopists to mitigate the risk.Trial registration number NCT01538550.

Background: Alcohol consumption is one of the major risk factors of colorectal cancer (CRC). However, the mechanisms underlying this relationship are not fully understood, particularly the potential role of gut microbes. 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: Participants included fecal immunochemical test-positive women and men enrolled in the CRCbiome study, aged 55-77 years at inclusion. Intake of alcohol was assessed using a validated, semi-quantitative food frequency questionnaire. Integrating with shotgun metagenome based taxonomic and functional profiles, we studied 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 1,468 participants with dietary data, 414 were diagnosed with advanced lesions (advanced adenoma, advanced serrated lesions or CRC). 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 (Log2 fold change (Log2FC) >0: B. finegoldii and L. asaccharolyticus; Log2FC <0: S. mutans, B. dentinum, C. symbiosum and E. boltae). A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria. Conclusions: Alcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions. ### Competing Interest Statement Dr. Mingyang Song serves as a consultant for Etiome Inc. The remaining authors declare no conflicts of interest. ### Funding Statement his project would not have been possible without funding from the Norwegian Cancer Society (grant nos. 190179 and 198048), the Norwegian Cancer Societys umbrella organization for cancer research (Kreftforeningens paraplystiftelse for kreftforskning), the Research Council of Norway (grant no. 280667) and the South-Eastern Norway Regional Health Authority (grant nos. 2022067 and 2020056). The BCSN trial study was funded by the Norwegian Parliament (Norwegian national budget from 2011). The bowel preparation used for colonoscopy was provided free of charge by Ferring Pharmaceuticals. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Both the BCSN and the CRCbiome study have been approved by the Regional Committee for Medical Research Ethics in South-East Norway (Approval no.: 2011/1272 and 63148, respectively). The BCSN is also registered at clinicaltrials.gov (Clinical Trial (NCT) no.: 01538550). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes DNA sequencing data analyzed in this study are deposited in the database Federated EGA under accession code EGAS50000000170 (https://ega-archive.org/studies/EGAS50000000170). Per participant consent, submitted FASTQ files exclude reads mapping to the human genome. The data are available under restricted access due to the sensitive nature of data derived from human subjects. Processing of data from this study must comply with the General Data Protection Regulation (GDPR). Access can be obtained by following the procedure described here: https://www.mn.uio.no/sbi/english/groups/roungegroup/crcbiome/. Requests for data access can also be directed to Trine B Rounge, trinro@uio.no.

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.

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.

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, semi-quantitative FFQ. Associations between meat intake and screen-detected colorectal lesions were examined using multinomial logistic regression analyses with adjustment for key covariates. Of 1162 participants, 319 presented with advanced colorectal lesions at colonoscopy. High v. 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 (OR of 1·24 (95 % CI 0·98, 1·57) and 1·34 (95 % CI 1·07, 1·69), respectively). A significant dose-response relationship was also observed for absolute intake levels (OR of 1·32 (95 % CI 1·09, 1·60) per 100 g/d 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 participants with absolute intake levels ≥ 100 v. < 50 g/d (OR of 1·19 (95 % CI 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 dietary data to improve the performance of FIT-based screening.

Faecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers for their stability and detectability. 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 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 the FIT leftover buffer, would be ideal due to its widespread use. In the present study, we applied small RNA sequencing to FIT leftover samples collected from two European screening populations. We showed robust detection of miRNA and microbial profiles, which were similar to those obtained from specimens sampled using RNA stabilising buffers and archived fecal samples. Detected miRNAs exhibited differential abundance between CRC and control samples that was consistent between sampling methods, suggesting a promising potential to identify small RNA CRC biomarkers using FIT leftovers. We demonstrated that it is possible to analyse gut miRNAs in FIT leftover samples and envision that these potential biomarkers can complement the FIT in large scale screening settings.

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.

IntroductionThe 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.MethodsBetween 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.ResultsOverall, 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.ConclusionsThese 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.

Letters28 November 2023Thyroidectomy for Euthyroid Patients With Hashimoto Disease and Persisting SymptomsGeir Hoff, MD, PhD*, Tomm Bernklev, PhD*, Lene Johnsen, MD, Laurens Reitsma, MD, Dirk Sina, MD, Andromeda Lauzike, MD, Charlotte Gibbs, MD, PhD, Eivind Carlsen, MD, Tone Hoel Lende, MD, PhD, Jon Kristian Narvestad, MD, Rasmus Kildahl, MD, Roald Omdal, MD, PhD, Jan Terje Kvaløy, PhD†, Håvard Søiland, MD, PhD†Geir Hoff, MD, PhD*Department of Research, Telemark Hospital, Skien, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway, Tomm Bernklev, PhD*Institute of Clinical Medicine, University of Oslo, Oslo, and Department of Research, Vestfold Hospital, Tønsberg, Norway, Lene Johnsen, MDDepartment of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway, Laurens Reitsma, MDDepartment of Breast and Endocrine Surgery, Akershus University Hospital, Campus Oslo, Lørenskog, Norway, Dirk Sina, MDDepartment of Breast and Endocrine Surgery, Telemark Hospital, Skien, Norway, Andromeda Lauzike, MDDepartment of Breast and Endocrine Surgery, Telemark Hospital, Skien, Norway, Charlotte Gibbs, MD, PhDDepartment of Medicine, Telemark Hospital, Skien, Norway, Eivind Carlsen, MDDepartment of Pathology, Telemark Hospital Skien, Norway, Tone Hoel Lende, MD, PhDDepartment of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway, Jon Kristian Narvestad, MDDepartment of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway, Rasmus Kildahl, MDDepartment of Surgery, Telemark Hospital, Skien, Norway, Roald Omdal, MD, PhDDepartment of Research, Stavanger University Hospital, Stavanger, and Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway, Jan Terje Kvaløy, PhD†Department of Research, Stavanger University Hospital, and Department of Mathematics and Physics, University of Stavanger, Stavanger, Norway, Håvard Søiland, MD, PhD†Department of Research, Stavanger University Hospital, Stavanger, and Department of Clinical Science, University of Bergen, Bergen, NorwayAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-1593 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Even when thyroxine is adequately replaced for hypothyroidism, patients with Hashimoto disease may report persistent extrathyroidal symptoms, including chronic fatigue, muscle and joint tenderness, dry mouth and eyes, and poor sleep quality (1).It has been hypothesized that these persistent symptoms may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms (2). This hypothesis was tested in a randomized trial of thyroidectomy plus medical management versus medical management alone with 18-month follow-up (3) (ClinicalTrials.gov: NCT02319538). At inclusion, patients in the control group were given the option of having ...References1. Punzi L, Betterle C. Chronic autoimmune thyroiditis and rheumatic manifestations. Joint Bone Spine. 2004;71:275-283. [PMID: 15288851] doi:10.1016/j.jbspin.2003.06.005 CrossrefMedlineGoogle Scholar2. Promberger R, Hermann M, Pallikunnel SJ, et al. Quality of life after thyroid surgery in women with benign euthyroid goiter: influencing factors including Hashimoto's thyroiditis. Am J Surg. 2014;207:974-979. [PMID: 24070662] doi:10.1016/j.amjsurg.2013.05.005 CrossrefMedlineGoogle Scholar3. Guldvog I, Reitsma LC, Johnsen L, et al. Thyroidectomy versus medical management for euthyroid patients with Hashimoto disease and persisting symptoms. A randomized trial. Ann Intern Med. 2019;170:453-464. [PMID: 30856652] doi:10.7326/M18-0284 LinkGoogle Scholar4. Liu T, Yu CP. Placebo analgesia, acupuncture and sham surgery. Evid Based Complement Alternat Med. 2011;2011:943147. [PMID: 21785643] doi:10.1093/ecam/neq030 CrossrefMedlineGoogle Scholar5. Wartolowska K, Judge A, Hopewell S, et al. Use of placebo controls in the evaluation of surgery: systematic review. BMJ. 2014;348:g3253. [PMID: 24850821] doi:10.1136/bmj.g3253 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Geir Hoff, MD, PhD; Tomm Bernklev, PhD; Lene Johnsen, MD; Laurens Reitsma, MD; Dirk Sina, MD; Andromeda Lauzike, MD; Charlotte Gibbs, MD, PhD; Eivind Carlsen, MD; Tone Hoel Lende, MD, PhD; Jon Kristian Narvestad, MD; Rasmus Kildahl, MD; Roald Omdal, MD, PhD; Jan Terje Kvaløy, PhD; Håvard Søiland, MD, PhDAffiliations: Department of Research, Telemark Hospital, Skien, and Institute of Clinical Medicine, University of Oslo, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, and Department of Research, Vestfold Hospital, Tønsberg, NorwayDepartment of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, NorwayDepartment of Breast and Endocrine Surgery, Akershus University Hospital, Campus Oslo, Lørenskog, NorwayDepartment of Breast and Endocrine Surgery, Telemark Hospital, Skien, NorwayDepartment of Medicine, Telemark Hospital, Skien, NorwayDepartment of Pathology, Telemark Hospital Skien, NorwayDepartment of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, NorwayDepartment of Surgery, Telemark Hospital, Skien, NorwayDepartment of Research, Stavanger University Hospital, Stavanger, and Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, NorwayDepartment of Research, Stavanger University Hospital, and Department of Mathematics and Physics, University of Stavanger, Stavanger, NorwayDepartment of Research, Stavanger University Hospital, Stavanger, and Department of Clinical Science, University of Bergen, Bergen, NorwayDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1593.Data Sharing Statement: The authors have indicated that they will not be sharing data. Additional context: There are restrictions by law in Norway making data sharing particularly difficult outside Norway.Corresponding Author: Geir Hoff, MD, PhD, Department of Research, Telemark Hospital, Vindalskroken 17, Skien, Norway 3728; e-mail, hofg@sthf.no.This article was published at Annals.org on 28 November 2023.* Drs. Hoff and Bernklev share first authorship.† Drs. Kvaløy and Søiland share senior authorship. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current Issue January 2024Volume 177, Issue 1 Page: 101-103 Keywords 36 item short form health survey Quality of life Randomized trials Sleep Thyroidectomy ePublished: 28 November 2023 Issue Published: January 2024 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...