Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer.

The fraction of patients who are cancer-free survivors 5 years after curative-intended surgery for colorectal cancer (CRC) is increasing, suggesting that extending surveillance beyond 5 years may be indicated. Here we estimate the incidence of late recurrence, metachronous CRC, and second primary cancers 5-10 years postoperative. All patients resected for UICC stage I-III CRC in Denmark through 2004-2013 were identified. Through individual-level linkage of nationwide health registry data, recurrence status was determined using a validated algorithm. Cancer-free survivors 5 years after surgery, were included. Cumulative incidence functions (CIF) of late recurrence, metachronous CRC, and second primary cancer 5-10 years postoperative were constructed. Subdistribution hazards ratios (sHR) were computed using Fine-Gray regression. Among 8883 patients, 370 developed late recurrence (5-10-year CIF = 4.1%, 95%CI: 3.7%-4.6%), 270 metachronous CRC (5-10-year CIF = 3.0%, 95%CI: 2.7%-3.4%), and 635 a second primary cancer (5-10-year CIF = 7.2%, 95%CI: 6.7%-7.7%). The risk of late recurrence was reduced for patients operated in 2009-2013 compared to 2004-2008 (2.9% vs. 5.6%, sHR = 0.52, 95% CI: 0.42-0.65). The risk of metachronous CRC was likewise reduced from 4.1% to 2.1% (sHR = 0.50, 95%CI: 0.39-0.65). While the risk of second primary cancer did not change between 2009-2013 and 2004-2008 (7.1% vs. 7.1%, sHR = 0.98, 95% CI: 0.84-1.15). Using nation-wide 10-year follow-up data, we document that the incidences of late recurrence and metachronous CRC are low and decreasing from 2004 to 2013. Thus, despite increasing numbers of long-term cancer survivors, the data do not advocate for extending CRC-specific surveillance beyond 5 years.

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study.

BACKGROUND & AIMS: Several studies have investigated the association between diverticular disease (DD) and colorectal cancer. However, whether there is an association between DD and malignancies other than those in the colorectum remains uncertain. METHODS: For the 1978-2019 period, we conducted a nationwide, population-based cohort study using national Danish health care data. We followed patients with DD for up to 20 years, beginning 1 year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among patients with DD with that in the general population. RESULTS: We identified 200,639 patients with DD, of whom 20,498 were diagnosed with cancer during the 1-20 years after their DD diagnosis. The SIRs were increased for most cancer sites except for those in the colorectum (SIR, 0.75; 95% confidence interval, 0.72-0.78). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% confidence interval, 1.15-1.24) and kidney (SIR, 1.27; 95% confidence interval, 1.16-1.39). CONCLUSIONS: Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely caused by prevalence of numerous risk factors in patients with DD that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of patients with DD undergoing colonoscopy with polypectomy.

Type 2 diabetes mellitus and post-colonoscopy colorectal cancer: clinical and molecular characteristics and survival.

PURPOSE: Studies suggest that patients with type two diabetes mellitus (T2D) may be at increased risk of post-colonoscopy colorectal cancer (PCCRC). We investigated clinical and molecular characteristics and survival of T2D patients with PCCRC to elucidate how T2D-related PCCRC may arise. METHODS: We identified T2D patients with colorectal cancer (CRC) from 1995 to 2015 and computed prevalence ratios (PRs) comparing clinical and molecular characteristics of CRC in T2D patients with PCCRC vs. in T2D patients with colonoscopy-detected CRC (dCRC). We also followed T2D patients from the diagnosis of PCCRC/dCRC until death, emigration, or study end and compared mortality using Cox-proportional hazards regression models adjusted for sex, age, year of CRC diagnosis, and CRC stage. RESULTS: Compared with dCRC, PCCRC was associated with a higher prevalence of proximal CRCs (54% vs. 40%; PR: 1.43, 95% confidence interval [CI] 1.27-1.62) in T2D patients. We found no difference between PCCRC vs. dCRC for CRC stage, histology, and mismatch repair status. The proportion of CRCs that could be categorized as PCCRC decreased over time. Within one year after CRC, 63% of PCCRC vs. 78% of dCRC patients were alive (hazard ratio [HR] 1.85 [95% CI 1.47-2.31]). Within five years after CRC, 44% of PCCRC vs. 54% of dCRC patients were still alive (HR 1.44 [95% CI 1.11-1.87]). CONCLUSION: The increased prevalence of proximally located PCCRCs and the poorer survival may suggest overlooked colorectal lesions as a predominant explanation for T2D-related PCCRC, although altered tumor progression cannot be ruled out.

Risk of a post-colonoscopy colorectal cancer in patients with diverticular disease: a population-based cohort study.

BACKGROUND: Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 30% of all colorectal cancers (CRCs) diagnosed in patients with diverticular disease; however, absolute and relative risks of PCCRC among these patients undergoing colonoscopy remain unknown. METHODS: We performed a cohort study (1995-2015) including patients with and without diverticular disease who underwent colonoscopy. We calculated 7-36-month cumulative incidence proportions (CIPs) of PCCRC. We used Cox proportional hazards regression models to compute hazard ratios (HRs) of PCCRC, comparing patients with and without diverticular disease, as a measure of relative risk. We calculated 3-year PCCRC rates, as per World Endoscopy Organization recommendations, to estimate the proportion of CRC patients with and without diverticular disease who were considered to have PCCRC. We stratified all analyses by PCCRC location. RESULTS: We observed 373 PCCRCs among 56 642 patients with diverticular disease and 1536 PCCRCs among 306 800 patients without diverticular disease. The PCCRC CIP after first-time colonoscopy was 0.45% (95%CI 0.40%-0.51%) for patients with and 0.36% (95%CI 0.34%-0.38%) for patients without diverticular disease. Comparing patients with and without diverticular disease undergoing first-time colonoscopy, the adjusted HR was 0.84 (95%CI 0.73-0.97) for PCCRC and 1.23 (95%CI 1.01-1.50) for proximal PCCRCs. The 3-year PCCRC rate was 19.0% (22.3% for proximal PCCRCs) for patients with and 6.5% for patients without diverticular disease. CONCLUSIONS: Although the absolute risk was low, the relative risk of proximal PCCRCs may be elevated in patients with diverticular disease undergoing colonoscopy compared with patients without the disease.

Diverticular disease and risk of dementia: a Danish population-based cohort study.

BACKGROUND AND AIM: Patients with diverticular disease (DD) have ongoing chronic inflammation associated with changes in the gut microbiome, which might contribute to the development of dementia. METHODS: Using Danish medical and administrative registries from 1980 to 2013, we conducted a nationwide population-based cohort study including all DD patients and a matched (5:1) general population comparison cohort without DD. A nested case-control analysis was then conducted using a risk set sampling, matching four DD controls without dementia to each DD patient with dementia. Clinical severity was categorized as uncomplicated DD (outpatient), conservatively treated DD (inpatient), and surgically treated DD. RESULTS: 149 527 DD patients and 747 635 general population comparators were identified. The 30-year cumulative incidence of dementia among DD patients and general population comparators were 12.4 (95% confidence interval [CI] 12.1-12.7) and 13.73% (95% CI 13.6-13.9), respectively. This corresponded to a 30-year hazard ratio (HR) of 1.10 (95% CI 1.1-1.1). The highest HRs were found in the conservatively treated DD group (1.15 95% CI 1.1-1.2) and the group with young onset of DD (1.52 95% CI 1.2-2.0). In the nested case-control analysis, we identified 8875 dementia cases and 35 491 matched controls. The adjusted odds ratio (OR) for conservatively treated DD was increased (1.08, 95% CI; 1.0-1.2) compared to the reference of uncomplicated DD. CONCLUSIONS: We observed a slight increased risk of dementia in patients with young onset DD and conservatively treated DD. Findings suggest an association between disease duration, perhaps reflecting the duration of gut inflammation, and the risk of developing dementia.

Rates of repeated colonoscopies to clean the colon from low-risk and high-risk adenomas: results from the EPoS trials.

OBJECTIVE: High-quality colonoscopy (adequate bowel preparation, whole-colon visualisation and removal of all neoplastic polyps) is a prerequisite to start polyp surveillance, and is ideally achieved in one colonoscopy. In a large multinational polyp surveillance trial, we aimed to investigate clinical practice variation in number of colonoscopies needed to enrol patients with low-risk and high-risk adenomas in polyp surveillance. DESIGN: We retrieved data of all patients with low-risk adenomas (one or two tubular adenomas <10 mm with low-grade dysplasia) and high-risk adenomas (3-10 adenomas, ≥1 adenoma ≥10 mm, high-grade dysplasia or villous components) in the European Polyp Surveillance trials fulfilling certain logistic and methodologic criteria. We analysed variations in number of colonoscopies needed to achieve high-quality colonoscopy and enter polyp surveillance by endoscopy centre, and by endoscopists who enrolled ≥30 patients. RESULTS: The study comprised 15 581 patients from 38 endoscopy centres in five European countries; 6794 patients had low-risk and 8787 had high-risk adenomas. 961 patients (6.2%, 95% CI 5.8% to 6.6%) underwent two or more colonoscopies before surveillance began; 101 (1.5%, 95% CI 1.2% to 1.8%) in the low-risk group and 860 (9.8%, 95% CI 9.2% to 10.4%) in the high-risk group. Main reasons were poor bowel preparation (21.3%) or incomplete colonoscopy/polypectomy (14.4%) or planned second procedure (27.8%). Need of repeat colonoscopy varied between study centres ranging from 0% to 11.8% in low-risk adenoma patients and from 0% to 63.9% in high-risk adenoma patients. On the second colonoscopy, the two most common reasons for a repeat (third) colonoscopy were piecemeal resection (26.5%) and unspecified reason (23.9%). CONCLUSION: There is considerable practice variation in the number of colonoscopies performed to achieve complete polyp removal, indicating need for targeted quality improvement to reduce patient burden. TRIAL REGISTRATION NUMBER: NCT02319928.

Effect of a FIT-Based Colorectal Cancer Screening Program on Mortality Estimated by the Regression Discontinuity Design.

The fecal immunochemical test (FIT) has been implemented in colorectal cancer (CRC) screening programs, but effect evaluations are lacking. We evaluated the effect of a positive FIT on all-cause and CRC mortality using the regression discontinuity design. The Danish CRC screening program invites all residents 50-74 years old, using a 20-µg hemoglobin/g feces cutoff for colonoscopy referral. In this cohort study, we followed all first-time screening participants from 2014-2019 until 2020. We estimated the local effect of screening results, of just above the cutoff vs. just below, as hazard ratios (HRs) between models fitted at each side of the cutoff. We conducted the analysis within a narrow hemoglobin range (≥17 and <23, n = 16,428) and a wider range (≥14 and <26, n = 35,353). Those screened just above the cutoff had lower all-cause mortality compared with below (HR = 0.87, 95% confidence interval: 0.69; 1.10), estimated from the narrow range. The CRC mortality analysis had few outcomes. In the wider range, those with a FIT just above the cutoff had a lower hazard of CRC mortality compared with just below the cutoff (HR = 0.49, 95% confidence interval: 0.17; 1.41). A FIT result just above the cutoff, leading to referral to colonoscopy, pointed towards reduced all-cause and CRC mortality compared with just below the cutoff.

Root-cause Analysis of 762 Danish Post-colonoscopy Colorectal Cancer Patients.

BACKGROUND & AIMS: The term post-colonoscopy colorectal cancer (PCCRC) refers to colorectal cancer (CRC) diagnosed after a negative colonoscopy. Using the root-cause algorithm proposed by the World Endoscopy Organization, we aimed to investigate plausible explanations for PCCRCs and potential changes in plausible explanations for PCCRCs over time in a Danish Region. METHODS: During 1995 to 2021, we used national health registries and electronic medical records in the Central Denmark Region to identify PCCRC cases, defined as CRCs recorded within 6 to 48 months after a colonoscopy. We then applied the World Endoscopy Organization algorithm to categorize explanations for PCCRC as follows: (A) possible missed lesion, prior examination adequate; (B) possible missed lesion, prior examination inadequate; (C) detected lesion, not resected; or (D) likely incomplete resection of previously identified lesion. PCCRCs were identified before (1995-2013) and after (2014-2021) implementation of nationwide fecal immunochemical test-based CRC screening and quality indicators for colonoscopy. RESULTS: We identified 762 PCCRCs, 53.5% among males and 57% among individuals ≥70 years. Forty-five percent were located in the proximal colon. We identified 616 (80.8%; 95% confidence interval [CI], 74.6%-87.5%) category A PCCRCs; 36 (4.7%; 95% CI, 3.3%-6.5%) category B PCCRCs; 26 (3.4%; 95% CI, 2.2%-4.9%) category C PCCRCs; and 84 (11%; 95% CI, 8.8%-13.6%) category D PCCRCs. Similar patterns were observed during the early (1995-2013) and late (2014-2021) study periods. CONCLUSIONS: Most PCCRCs originate from possible missed lesions and incompletely resected lesions during the complete study period. These findings indicate the importance of quality assurance of colonoscopy procedures and polypectomy techniques.

Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study.

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

Prenatal, Intrapartum, and Neonatal Factors Increase the Risk of Eosinophilic Esophagitis.

INTRODUCTION: Early-life exposures have been associated with an increased risk of eosinophilic esophagitis (EoE); however, most studies to date have been conducted at referral centers and are subject to recall bias. By contrast, we conducted a nationwide, population-based and registry-based case-control study of prenatal, intrapartum, and neonatal exposures, using data collected prospectively through population-based Danish health and administrative registries. METHODS: We ascertained all EoE cases in Denmark (birth years 1997-2018). Cases were sex and age matched to controls (1:10) using risk-set sampling. We obtained data on prenatal, intrapartum, and neonatal factors, i.e., pregnancy complications, mode of delivery, gestational age at delivery, birthweight (expressed as a z-score), and neonatal intensive care unit (NICU) admission. We used conditional logistic regression to compute the crude and adjusted odds ratios (aOR) of EoE in relation to each prenatal, intrapartum, and neonatal factor, thus providing an estimate of incidence density ratios with 95% confidence intervals (CI). RESULTS: In the 393 cases and 3,659 population controls included (median age at index date, 11 years [interquartile range, 6-15]; 69% male), we observed an association between gestational age and EoE, peaking at 33 vs 40 weeks (aOR 3.6 [95% CI 1.8-7.4]), and between NICU admission and EoE (aOR 2.8 [95% CI 1.2-6.6], for a NICU hospitalization of 2-3 weeks vs no admission). In interaction analyses, we observed a stronger association between NICU admission and EoE in infants born at term than in preterm infants (aOR 2.0 [95% CI 1.4-2.9] for term infants and aOR 1.0 [95% CI 0.5-2.0] for preterm infants). We also observed an association between pregnancy complications and EoE (aOR 1.4 [95% CI 1.0-1.9]). Infants who were very growth restricted at birth had an increased rate of EoE (aOR 1.4 [95% CI: 1.0-1.9] for a z-score of -1.5 vs a z-score of 0). Mode of delivery was not associated with EoE. DISCUSSION: Prenatal, intrapartum, and neonatal factors, particularly preterm birth and NICU admission, were associated with development of EoE. Further research is needed to elucidate the mechanisms underlying the observed associations.

Risk of incisional hernia repair in patients with inflammatory bowel disease.

AIM: Patients with inflammatory bowel disease (IBD) may undergo several abdominal surgeries with a risk of incisional hernia repair (IHR). The objectives of this study were to establish the risk of IHR and to analyse predictors of IHR after a first-time abdominal surgery for IBD. METHOD: This Danish nationwide register-based cohort study (1996-2018) followed IBD patients from index operation until the date of IHR. The absolute risk was calculated as the cumulative incidence proportion treating death as a competing risk. Cox proportional hazard regression was used to compare the risk of IHR among different subtypes of IBD and to explore predictors of IHR. IBD subtypes were classified as ulcerative colitis (UC), Crohn's disease (CD) or unclassified IBD (IBD-U). RESULTS: In total, 10 130 patients with IBD (UC 3911 [39%]; CD 4210 [41%]; IBD-U 2009 [20%]) underwent either an open or a laparoscopic index operation. The 10-year cumulative incidence of IHR varied between 5.0% and 6.3%, with a significantly higher risk in patients with UC and IBD-U. Patients with UC (75.9%) and IBD-U (91.9%) had more (two or more) abdominal surgeries in the follow-up period compared with CD (51.9%). The risk of IHR increased dramatically with the number of surgeries, although not as markedly if a laparoscopic approach was used. Male sex, age, comorbidity, fascial dehiscence, wound infection and presence of stoma were predictors of IHR for patients with IBD. CONCLUSION: The long-term risk of IHR was roughly 5%-6%, with a higher risk in patients with UC and IBD-U. Open surgical approach and number of previous surgeries were, among other things, important predictors of IHR.

Short-term outcomes following total colectomy for inflammatory bowel disease in Denmark after implementation of laparoscopy: a nationwide population-based study.

AIM: A laparoscopic approach to total colectomy (TC) for inflammatory bowel disease (IBD) is being increasingly used, but data on its comparative benefits over open TC are conflicting. The aim of this study was to examine 90-day outcomes following laparoscopic and open TC for IBD in a nationwide cohort after the introduction of laparoscopy. METHOD: IBD patients undergoing TC in Denmark from 2005 to 2017 were identified from the Danish National Patient Registry. We used Kaplan-Meier methodology to estimate mortality and Cox regression analysis to estimate adjusted mortality rate ratios (aMRRs) and adjusted hazard ratios (aHRs) of reoperation, readmission and intensive care unit (ICU) transfer, comparing patients undergoing laparoscopic versus open TC. RESULTS: We identified 1095 patients undergoing laparoscopic TC and 1523 patients undergoing open TC. Following emergency TC, 90-day mortality was 2.8% (1.6%-4.9%) after laparoscopic TC and 9.1% (7.0%-11.8%) after open TC. Ninety-day mortality was 0.9% (0.3%-2.5%) after laparoscopic TC and 2.6% (1.5%-4.3%) after open elective TC. The aMRRs associated with laparoscopic TC were 0.45 (95% CI 0.25-0.80) in emergency cases and 0.29 (95% CI 0.10-0.86) in elective cases. Risks of readmission were comparable following laparoscopic versus open TC, both in emergency [aHR = 0.93 (95% CI 0.76-1.15)] and elective [aHR = 0.83 (95% CI 0.68-1.02)] cases, while risks of ICU transfer and reoperation were lower following laparoscopic TC, both in emergency cases [aHR = 0.53 (95% CI 0.35-0.82) and aHR = 0.26 (95% CI 0.15-0.47)] and elective [aHR = 0.58 (95% CI 0.35-0.95) and aHR = 0.37 (95% CI 0.21-0.66)] cases. CONCLUSION: The introduction of laparoscopic TC for IBD in Denmark was not associated with increased mortality or morbidity. In fact, laparoscopic TC for IBD may be associated with lower short-term mortality and morbidity compared with open TC.

Risk-stratified selection to colonoscopy in FIT colorectal cancer screening: development and temporal validation of a prediction model.

BACKGROUND: Faecal immunochemical tests (FITs) yield many false positives and challenge colonoscopy capacity in colorectal cancer (CRC) screening programmes. We aimed to develop a risk-based selection of participants to undergo diagnostic colonoscopy. METHODS: The study was observational and used registry data from the Danish CRC screening programme. We included all participants invited 2014-2016 with a positive FIT (≥ 20 µg fHb/g) who underwent colonoscopy (n = 56,459). We predicted the risk of CRC or advanced neoplasia (AN) from age, gender and FIT value using logistic regression. We evaluated calibration and discrimination and conducted temporal validation. We compared the number of CRCs and adenomas identified by risk cut-offs and by a corresponding FIT cut-off. RESULTS: AUCs were 74.9% (95% CI: 73.6; 76.3) and 67.4% (95% CI: 66.8%; 68.0%) for the models predicting CRC and AN in the validation dataset. The cut-off of CRC risk calculated from age, gender and FIT value identified 1.03 times (95% CI: 1.02; 1.05) more CRCs and 1.01 times (95% CI: 1.01; 1.01) more medium/high-risk adenomas compared with the corresponding FIT cut-off. CONCLUSIONS: With existing data, risk-stratified FIT screening using a risk cut-off instead of a FIT cut-off can slightly improve the selection to colonoscopy of those at highest risk of cancer and adenomas.

Characteristics and Survival of Patients With Inflammatory Bowel Disease and Postcolonoscopy Colorectal Cancers.

BACKGROUND & AIMS: Postcolonoscopy colorectal cancers (PCCRCs) account for up to 50% of colorectal cancers (CRCs) in patients with inflammatory bowel disease (IBD). We investigated characteristics of IBD patients with PCCRC and their survival. METHODS: We identified IBD patients (ulcerative colitis [UC] and Crohn's disease) diagnosed with CRC from 1995 to 2015. We defined PCCRC as diagnosed between 6 and 36 months, and detected CRC (dCRC) as diagnosed within 6 months after colonoscopy. We computed prevalence ratios comparing PCCRC vs dCRC and followed up patients from the diagnosis of PCCRC/dCRC until death, emigration, or study end. Mortality was compared using Cox proportional hazards regression models adjusted for sex, age, year of CRC diagnosis, and stage. The main analyses focused on patients with UC. RESULTS: Among 23,738 UC patients undergoing colonoscopy, we identified 352 patients with CRC, of whom 103 (29%) had PCCRC. Compared with dCRC, PCCRC was associated with a higher prevalence of metastatic cancer (33% vs 20%; prevalence ratio, 1.64; 95% CI, 1.13-2.38), cancers showing mismatch repair deficiency (79% vs 56%; prevalence ratio, 1.40; 95% CI, 1.13-1.72), and proximally located cancers (54% vs 40%; prevalence ratio, 1.34; 95% CI, 1.06-1.69). The 1- and 5-year adjusted hazard ratios of death for PCCRC vs dCRC among UC patients were 1.29 (95% CI, 0.77-2.18) and 1.24 (95% CI, 0.86-1.79), respectively. CONCLUSIONS: The characteristics of UC-related PCCRC suggest tumor biology as an important factor in the progression to cancer. However, the prognosis of PCCRC appears similar to that of dCRC.

Mental illness and participation in colorectal cancer screening: a scoping review.

INTRODUCTION: Compared with the background population, persons with mental illness have increased colorectal cancer (CRC) mortality. Screening has the potential to alleviate the increased cancer mortality due to mental illness, but the extent to which persons with mental illness participate in CRC screening programs is uncertain. This scoping review aims to summarize the literature on CRC screening participation among persons with mental illness. MATERIALS AND METHODS: We searched four databases (PubMed, PsychInfo, Embase, and the Cochrane Library) to identify published literature on mental illness and participation in CRC screening programs. We included full-text papers available in English, published before February 2021, and excluded papers on dementia, intellectual disabilities, and developmental disabilities. RESULTS: In total, we included 17 studies and categorized the findings according to severity of mental illness. Across varying study designs, the studies found that persons with severe mental illness, e.g. schizophrenia, participate less in CRC screening compared with the background population. The results were ambiguous for common mental illness, such as depression and anxiety. In general, studies were small or lacked comparison groups and the estimates were imprecise. CONCLUSION: This is the first scoping review to evaluate participation in CRC screening programs among persons with mental illness. Overall, the existing literature lacks high quality evidence from large population-based studies and comparison groups based on organized screening programs.

The impact of multiple firings on the risk of anastomotic leakage after minimally invasive restorative rectal cancer resection and the impact of anastomotic leakage on long-term survival: a population-based study.

PURPOSE: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival. METHODS: The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan-Meier methods and Cox regression. RESULTS: AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3-24.3) and 5.0% (95% CI 2.4-9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12-0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17-6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1-84.0) and 83.6% (95%CI 79.8-86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84-2.41). CONCLUSION: Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival.

Colorectal Cancer in Childhood-onset Inflammatory Bowel Disease: A Scandinavian Register-based Cohort Study, 1969-2017.

Through linkage of data from Danish and Swedish national registers we identified 6937 patients with childhood (<18 years)-onset Crohn disease (CD), 8514 patients with childhood-onset ulcerative colitis (UC) and up to 10 times as many matched (sex, age, residence) reference individuals 1969-2017. During follow-up to a median age of 27 (interquartile range = 21-39) years, 25 (0.36%) CD patients were diagnosed with colorectal cancer (CRC) versus 43 (0.06%) reference individuals, and 113 (1.33%) UC patients versus 45 (0.05%) reference individuals. The hazard ratio (HR) for CRC was 6.46 (95% CI = 3.95-10.6) in CD and 32.5 (95% CI = 23.0-45.9) in UC and increased with decreasing age at diagnosis. The HR for CRC was increased for all phenotypes, but with higher estimates for colonic CD [17.9 (95% CI = 7.43-43.3)] and UC with extensive/pancolitis [36.3 (95% CI = 22.8-57.8)]. The relative risk of CRC was increased for all phenotypes of childhood-onset inflammatory bowel disease. Age at onset may be considered an additional risk factor when implementing surveillance programs.

Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden.

OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs). RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32). CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

Colorectal cancer in ulcerative colitis: a Scandinavian population-based cohort study.

BACKGROUND: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC. METHODS: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account. FINDINGS: During follow-up, we observed 1336 incident CRCs in the UC cohort (1·29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0·82 per 1000 person-years; HR 1·66, 95% CI 1·57-1·76). In the UC cohort, 639 patients died from CRC (0·55 per 1000 person-years), compared with 4451 reference individuals (0·38 per 1000 person-years; HR 1·59, 95% CI 1·46-1·72) during the same time period. The CRC stage distribution in people with UC was less advanced (p<0·0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1·54, 95% CI 1·33-1·78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1·38 (95% CI 1·20-1·60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1·25 (95% CI 1·03-1·51, or one additional case per 3041 patients with UC per 5 years). INTERPRETATION: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines. FUNDING: The Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation, Swedish Cancer Foundation.

Risk of a post-colonoscopy colorectal cancer diagnosis in patients with inflammatory bowel disease: a population-based cohort study.

BACKGROUND : Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 50 % of all colorectal cancers (CRCs) diagnosed in patients with inflammatory bowel disease (IBD). This may reflect a high colonoscopy frequency; however, evidence remains limited. METHODS : We conducted a cohort study of IBD and non-IBD patients undergoing colonoscopy. We calculated cumulative incidence proportions (CIPs) of PCCRC at 7-36 months after first-time and subsequent colonoscopies. We also computed crude and adjusted hazard ratios (HRs) of PCCRC, comparing IBD with non-IBD patients undergoing first-time and subsequent colonoscopies. Separate analyses were conducted for consecutive colonoscopies. We calculated 3-year rates of PCCRC to estimate the proportion of IBD and non-IBD CRC patients experiencing PCCRC. RESULTS : We observed 138 and 1909 PCCRCs among 34 688 IBD and 358 217 non-IBD patients who underwent colonoscopy. The CIP of PCCRC after first-time colonoscopy was 0.21 % (95 % confidence interval [CI] 0.17 %-0.27 %) for IBD patients and 0.37 % (95 %CI 0.35 %-0.39 %) for non-IBD patients. The adjusted HR of PCCRC after a first-time colonoscopy was 0.96 (95 %CI 0.75-1.22) and the adjusted HRs after subsequent colonoscopies had point estimates around 1.0. The 3-year PCCRC rate was 24.3 % (95 %CI 20.4 %-28.7 %) for IBD and 7.5 % (95 %CI 7.2 %-7.8 %) for non-IBD patients. CONCLUSIONS : Although PCCRCs accounted for a substantial proportion of all IBD-related CRCs, IBD patients had a low CIP of PCCRC. The elevated 3-year PCCRC rates may, among other factors, stem from the increased colonoscopy frequency in IBD patients.