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 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.

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.

Cohort Profile: Better Health in Late Life.

Purpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. Methods: A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Venous Thromboembolism and Risk of Cancer in Users of Low-Dose Aspirin: A Danish Population-Based Cohort Study.

Background Aspirin may reduce the risk of cancer, particularly gastrointestinal cancer, and venous thromboembolism (VTE). VTE can be the first symptom of occult cancer, but whether it is also a marker of occult cancer in aspirin users remains unknown. Therefore, we investigated the risk of cancer subsequent to VTE among users of low-dose aspirin. Methods We conducted a population-based cohort study using data from Danish health registries for the years 2001 to 2018. We identified all patients with a first-time diagnosis of VTE who also redeemed a prescription for low-dose aspirin (75-150mg) within 90 days prior to the first-time VTE. We categorized aspirin users by the number of prescriptions filled as new users (<5 prescriptions), short-term users (5-19 prescriptions), and long-term users (>19 prescriptions). We computed the absolute cancer risks and standardized incidence ratios (SIRs) for cancer using national cancer incidence rates. Results We followed-up 11,759 users of low-dose aspirin with VTE. Long-term users comprised 50% of aspirin users. The 1-year absolute risk of cancer was 6.0% for new users and 6.7% for short-term and long-term users, with corresponding SIRs of 3.3 (95% confidence interval [CI]: 2.8-4.0), 3.2 (95% CI: 2.9-3.7), and 2.8 (95% CI: 2.6-3.2), respectively. After the first year of follow-up, the SIR decreased to 1.2 (95% CI: 1.1-1.4) for new users, 1.1 (95% CI: 1.1-1.3) for short-term users, and 1.1 (95% CI: 1.0-1.2) for long-term users. Conclusion VTE may be a harbinger of cancer, even in users of low-dose aspirin, regardless of duration of use.

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.

Venous Thromboembolism and Risk of Cancer in Patients with Dementia: A Danish Population-Based Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) may be the first manifestation of occult cancer. Dementia has been linked to reduced cancer risk. OBJECTIVE: We examined the risk of cancer following VTE in people with dementia in comparison to the risk in the general population. METHODS: We conducted a population-based Danish registry-based cohort study following patients with a first-time VTE and a previous or concurrent diagnosis of dementia during the period 1 April 1996 -31 December 2017. We followed the study participants from date of VTE until diagnosis of cancer, death, emigration, or end of study period, whichever came first. The absolute risk of cancer within one year after VTE was computed, treating death as a competing risk. We calculated gender, age, and calendar-period standardized incidence ratios (SIRs) of cancer based on national cancer rates. RESULTS: We followed 3,552 people with dementia and VTE for a median of 1.3 years. Within the first year after VTE, they had a 90% increased risk of cancer in comparison with the general population [SIR: 1.9 (95% confidence interval: 1.6-2.4)]. During subsequent follow-up years, the SIR fell to 0.7 (95% confidence interval: 0.5-0.8). Findings for Alzheimer's disease and VTE were similar. CONCLUSION: People with dementia have an increased risk of a cancer diagnosis during the first year following VTE, perhaps related to increased surveillance, and a lower risk thereafter. Overall risk is similar to that of the general population.

Prevalence of Colorectal Neoplasms and Mortality in New Users of Low-Dose Aspirin With Lower Gastrointestinal Bleeding.

BACKGROUND: Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection. STUDY QUESTION: To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients. STUDY DESIGN: Using Danish nationwide health registries, we conducted a cohort study (2006-2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date. MEASURES AND OUTCOMES: We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers. RESULTS: We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06-1.55]} and serrated [PR = 1.31 (95% CI: 0.95-1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77-1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35-1.43)] in new users than in nonusers. No difference in mortality was observed. CONCLUSIONS: These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.