BackgroundCigarette smoking is an established risk factor for colorectal cancer. Because colorectal carcinogenesis is a heterogeneous process, we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer. MethodsWe evaluated associations between smoking and incident colorectal cancer, overall and by microsatellite instability (MSI) phenotype (MSI-high vs MSI-low or microsatellite stable), CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation status (BRAF mutation positive or BRAF mutation negative), among 37 399 participants in a population-based cohort study (the Iowa Women's Health Study). Cigarette smoking (and other exposures) was assessed by self-report at baseline in 1986, including smoking status (never and ever [former or current]), age at initiation, total duration, average number of cigarettes smoked per day, cumulative pack-years, and induction period. Vital status and state of residence were determined by mailed follow-up questionnaires in 1987, 1989, 1992, and 1997 and by linkage to Iowa death certificate records. Nonrespondents were checked via the National Death Index to identify descendants. Participants with newly diagnosed (ie, incident) colorectal cancer were identified through annual linkage with the Iowa Cancer Registry. Archived paraffin-embedded tumor tissue specimens were obtained for 555 patients with colorectal cancer who were diagnosed from January 1, 1986, through December 31, 2002, and MSI status, CIMP status, and BRAF status were determined. Multivariable Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs). ResultsEver-smokers were at moderately increased risk for incident colorectal cancer (RR = 1.19, 95% CI = 1.05 to 1.35) compared with never-smokers. Higher risk estimates were observed for current smokers with MSI-high tumors (RR = 1.99, 95% CI = 1.26 to 3.14), CIMP-positive tumors (RR = 1.88, 95% CI = 1.22 to 2.90), and BRAF mutationpositive tumors (RR = 1.92, 95% CI = 1.22 to 3.02). Other smoking-related variables (ie, age at initiation, total duration, average number of cigarettes smoked per day, cumulative pack-years, and induction period) were also associated with MSI-high, CIMP-positive, and BRAF mutation-positive tumor subtypes. Conversely, cigarette smoking status (ever vs never) was not associated with the MSI-low or microsatellite stable (RR = 1.00, 95% CI = 0.79 to 1.25), CIMP-negative (RR = 1.02, 95% CI = 0.81 to 1.30), or BRAF mutation-negative subtypes (RR = 1.00, 95% CI = 0.65 to 1.27). ConclusionsIn this prospective study of older women, cigarette smoking was associated with the MSI-high, CIMP-positive, and BRAF mutation-positive colorectal cancer subtypes, which indicates that epigenetic modification may be functionally involved in smoking-related colorectal carcinogenesis. Risk Factor AssessmentCigarette smoking patterns among IWHS participants were comprehensively ascertained at baseline in 1986, including smoking statu...
In this population-based cohort of histologically confirmed microscopic colitis, approximately one-half met symptom-based criteria for the diagnosis of irritable bowel syndrome. The clinical symptom-based criteria for irritable bowel syndrome are not specific enough to rule out the diagnosis of microscopic colitis. Therefore, patients with suspected diarrhea-predominant irritable bowel syndrome should undergo biopsies of the colon to investigate for possible microscopic colitis if symptoms are not well controlled by antidiarrheal therapy.
Background Postmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive. Objectives To evaluate associations between PMH therapy and incident CRC, overall and by molecularly defined subtypes, in the population-based Iowa Women’s Health Study of older women. Methods Exposure data were collected from Iowa Women’s Health Study participants (55–69 years) at baseline (1986). Archived, paraffin-embedded tissue specimens for 553 CRC cases were collected and analysed to determine microsatellite instability (MSI-L/MSS or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive) and BRAF mutation (BRAF-wildtype or BRAF-mutated) status. Multivariable Cox regression models were fit to estimate RRs and 95% CIs. Results PMH therapy (ever vs never use) was inversely associated with incident CRC overall (RR=0.82; 95% CI 0.72 to 0.93), with a significantly lower risk for MSI-L/MSS tumours (RR=0.75; 95% CI 0.60 to 0.94), and borderline significantly lower risks for CIMP-negative (RR=0.79; 95% CI 0.63 to 1.01) and BRAF-wildtype (RR=0.83; 95% CI 0.66 to 1.04) tumours. For PMH therapy >5 years, the subtype-specific risk estimates for MSI-L/MSS, CIMP-negative and BRAF-wildtype tumours were: RR=0.60, 95% CI 0.40 to 0.91; RR=0.68, 95% CI 0.45 to 1.03; and RR=0.70, 95% CI 0.47 to 1.05, respectively. PMH therapy was not significantly associated with the MSI-H, CIMP-positive or BRAF-mutated CRC subtypes. Conclusions In this prospective cohort study, PMH therapy was inversely associated with distinct molecularly defined CRC subtypes, which may be related to differential effects from oestrogen and/or progestin on heterogeneous pathways of colorectal carcinogenesis.
GS was common in IBD and associated with having had a recent flare. GS may be transient for some patients, whereby dietary recommendations during and after a flare could focus on the avoidance of specific food triggers with possible reintroduction of these foods over time. This study prompts further prospective investigation into the temporal evolution of GS in IBD.
Vitamin D is a secosteroid hormone that possesses immunomodulatory properties and has been demonstrated to potentially influence inflammatory bowel disease (IBD) pathogenesis and activity. Epidemiologic data have associated vitamin D deficiency with an increased risk of IBD, hospitalizations, surgery, and loss of response to biologic therapy. Conversely, IBD itself can lead to vitamin D deficiency. This bidirectional relationship between vitamin D and IBD suggests the need for monitoring and repletion of vitamin D, as needed, in the IBD patient. This review discusses the role of vitamin D in IBD and provides practical guidance on vitamin D repletion.
The incidence of intestinal infections among hospitalized IBD patients has increased over the past 15 years, primarily driven by C. difficile infections. Intestinal infections are associated with length of stay, hospital charges, and all-cause mortality. More aggressive measures for prevention of C. difficile infections are needed. 10.1093/ibd/izy086_video1izy086.video15779257979001.
AimTo prospectively evaluate the effects of vitamin D3 on disease activity and quality of life in ulcerative colitis (UC) patients with hypovitaminosis D.MethodsThe study was a prospective double-blinded, randomized trial conducted at Community Regional Medical Center, Fresno, CA from 2012–2013. Patients with UC and a serum 25(OH)D level <30 ng/ml were eligible for the study. Enrolled subjects were randomized to receive either 2,000 IU or 4,000 IU of oral vitamin D3 daily for a total of 90 days. The Short IBD Questionnaire (SIBDQ) for quality of life, the Partial Mayo Score for UC disease activity and serum lab tests were compared between the two treatment groups. Matched pair t-tests were computed to assess differences between the vitamin D levels, CRP, UC disease activity and SIBDQ scores before and after vitamin D3 therapy using SPSS version 21.ResultsEight UC patients received 2,000 IU/daily and ten UC patients received 4,000 IU/daily of vitamin D3 for 90 days. Vitamin D levels increased after 90 days of oral vitamin D3 in both dose groups. However, the increase in vitamin D levels after 90 days of oral vitamin D3, in the 4,000 IU group was significantly higher 16.80 ± 9.15 (p < 0.001) compared to the 2,000 IU group of vitamin D 5.00 ± 3.12 (p = 0.008). Normal vitamin D levels (>30 ng/dl) were achieved in four out of the ten UC patients (40%) in the 4,000 IU group and in one out of the eight UC patients (12%) in the 2,000 IU group. In the group receiving 4,000 IU/day of vitamin D3 the increase in quality life scores (SIBDQ) was significant 1.0 ± 1.0 (p = 0.017) but not in the 2,000 IU vitamin D3 group 0.1 ± 1.0 (p = 0.87). In the 2,000 IU of vitamin D3 group the mean decrease in the Partial Mayo UC Score was −0.5 ± 1.5 (p = 0.38) compared to −1.3 ± 2.9 (p = 0.19) in the 4,000 IU vitamin D3 group but this was not statistically significant. CRP levels decreased after 90 days of daily vitamin D3 in both the 2,000 IU group and 4,000 IU group by −3.0 ± 9.4 (p = 0.4) and −10.8 ± 35.0 (p = 0.36) respectively.ConclusionVitamin D3 at 4,000 IU/day is more effective than 2,000 IU/day in increasing vitamin D to sufficient levels in UC patients with hypovitaminosis D, however higher doses or treatment beyond ninety days may be required. Vitamin D3 may improve the quality of life in UC patients but clinically significant improvement is not yet established. The effect of vitamin D3 on UC disease activity is still unclear. Further larger studies are needed to investigate the effects of vitamin D in ulcerative colitis.
Both interobserver and intraobserver agreement were good in distinguishing among the 6 diagnostic categories, and excellent in distinguishing between microscopic colitis and nonmicroscopic colitis diagnoses. The histologic criteria for microscopic colitis provide for consistent and reproducible interindividual and intraindividual diagnoses in the evaluation of colonic biopsies.
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