Project description:BackgroundGender dysphoria could be associated with low socioeconomic status (SES). SES could be modified by age, ethnic background, and medical morbidity.AimTo determine SES in a national study population including transgender persons in Denmark.MethodsNational register-based cohort study in Danish transgender persons and age-matched controls. The transgender study cohort included persons with ICD-10 diagnosis code of 'gender identity disorder' and/or persons with legal sex change and persons who fulfiled the inclusion criteria during 2000-2018. The main outcome measure was SES including personal income, occupational status, and education.ResultsThe cohort included 2770 transgender persons and 27,700 controls. In the transgender study cohort, 1437 were assigned male at birth (AMAB), median age (interquartile range, IQR) 26.0 (17.3) years, and 1333 were assigned female at birth (AFAB), median age 22.5 (10.3) years. Adjusting for age and sex, the relative risk ratio (RRR) of low vs high personal income was 5.6 (95% CI: 4.9; 6.3) in transgender persons compared to controls. The RRR of low vs high income was 6.9 (5.8; 8.3) in persons AMAB compared to control males and 4.7 (3.9; 5.6) in persons AFAB compared to control females. The RRR of low vs high income was 3.7 (3.2; 4.3) in transgender persons of Danish origin compared to controls. The Charlson comorbidity index was comparable in transgender persons vs controls.ConclusionsBeing transgender was negatively associated with SES. In transgender persons, the risk of low vs high income could be more pronounced in transgender persons of foreign origin.
Project description:Background and study aims The risk of developing total metachronous advanced neoplasia (TMAN) in patients with index serrated lesions (SL) or adenoma with high-grade dysplasia (HGD) is unknown. We evaluated this risk in patients with either HGD, SL < 10 mm or SL ≥ 10 mm at index colonoscopy, who underwent surveillance colonoscopies. Patients and methods This retrospective cohort study evaluated all consecutive patients (n = 2477) diagnosed between 2010 and 2019 with colorectal HGD, SLs < 10 mm or SLs ≥ 10 mm. We excluded patients aged < 45 or > 75 years or those who had inflammatory bowel disease, hereditary colorectal cancer (CRC) syndromes, previous or synchronous CRC, or no follow-up colonoscopy. Descriptive variables were compared using analysis of variance or Pearson chi-squared tests. Multivariate Cox regressions were used to compare the risk of TMAN between the HGD, SL < 10 mm and SL ≥ 10 mm groups. Results Overall, 585 patients (mean age 63 years; 55% male; mean follow-up 3.67 years) were included (226 with SLs < 10 mm, 204 with SLs ≥ 10 mm, 155 with HGD). Compared with SLs < 10 mm, patients with HGD did not have a significantly different rate of TMAN (HR=0.75 [0.39-1.44]) and patients with SLs ≥ 10 mm had a higher rate of TMAN (HR=2.08 [1.38-3.15]). Compared with HGD, patients with SLs ≥ 10 mm had a higher rate of TMAN (HR=1.87 [1.04-3.36]). Conclusions The risk for TMAN was higher for patients with SLs ≥ 10 mm than with HGD or SLs < 10 mm. This risk should be considered when planning surveillance intervals for patients diagnosed with large SLs.
Project description:BackgroundInflammatory bowel disease [IBD] has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear.MethodsWe identified 41 880 individuals with IBD (Crohn's disease [CD: n = 12 850]; ulcerative colitis [UC]: n = 29 030]) from Sweden matched with 41 880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios [aHRs] for neoplastic colorectal polyps [tubular, serrated/sessile, advanced and villous] defined by histopathology codes.ResultsDuring follow-up, 1648 [3.9%] IBD patients and 1143 [2.7%] reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10 000 person-years, respectively. This correlated to an aHR of 1.23 (95% confidence interval [CI] 1.12-1.35) with the highest HRs seen for sessile serrated polyps [8.50, 95% CI 1.10-65.90] and traditional serrated adenomas [1.72, 95% CI 1.02-2.91]. aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and at 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD [aHRs 1.31 vs 1.06, respectively], with a 20-year cumulative risk difference of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis.ConclusionsIn this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.
Project description:ObjectivesEndoscopist quality measures such as adenoma detection rate (ADR) and serrated polyp detection rates (SPDRs) depend on pathologist classification of histology. Although variation in pathologic interpretation is recognized, we add to the literature by quantifying the impact of pathologic variability on endoscopist performance.MethodsWe used natural language processing to abstract relevant data from colonoscopy and related pathology reports performed over 2 years at four clinical sites. We quantified each pathologist's likelihood of classifying polyp specimens as adenomas or serrated polyps. We estimated the impact on endoscopists' ADR and SPDR of sending their specimens to pathologists with higher or lower classification rates.ResultsWe observed 85,526 colonoscopies performed by 119 endoscopists; 50,453 had a polyp specimen, which were analyzed by 48 pathologists. There was greater variation across pathologists in classification of serrated polyps than in classification of adenomas. We estimate the endoscopist's average SPDR would be 0.5% if all their specimens were analyzed by the pathologist in our sample with the lowest classification rate and 12.0% if all their specimens were analyzed by the pathologist with the highest classification rate. In contrast, the endoscopist's average ADR would be 28.5% and 42.4% if their specimens were analyzed by the pathologist with lowest and highest classification rate, respectively.ConclusionsThere is significant variation in pathologic interpretation, which more substantially affects endoscopist SPDR than ADR.
Project description:AimThe aim of this study was to investigate the trends in morbidity and mortality of patients with right-sided colonic cancer who had an emergency surgical procedure in Denmark after the introduction of quality index parameters.MethodsThis was a retrospective nationwide study based on a prospectively maintained Danish Colorectal Cancer Group database focused on right-sided colonic cancer in the interval from 1 May 2001 to 30 April 2018, who underwent emergency surgical intervention (within 48 h of hospital admission). The primary objective was to investigate the trends in morbidity and mortality throughout the study years. Multivariable estimates were adjusted for age, sex, smoking status, alcohol consumption, ASA score classification, tumour localization, type of access to abdominal cavity, surgeon's grade of specialization, and metastatic disease.ResultsOut of 2839 patients, a total of 2740 patients fulfilled the inclusion criteria, of whom 2464 underwent right or transverse colon resection (89.9 per cent). The 30-day and 90-day postoperative mortality rates were significantly reduced over the time of the study (OR 0.943, 95 per cent c.i. 0.922 to 0.965, P < 0.001 and OR 0.953, 95 per cent c.i. 0.934 to 0.972, P < 0.001 respectively); however, the complication rates did not follow this trend. Older patients (OR 1.032, 95 per cent c.i. 1.009 to 1.055, P = 0.005) and patients with high ASA scores (OR 1.61, 95 per cent c.i. 1.422 to 1.830, P < 0.001) had higher rates of severe grade 3b postoperative complications. A stoma was constructed in 276 patients (10 per cent), whereas a stent was used in only eight patients. Defunctioning procedures, including stoma construction or colonic stenting (without oncological resection), did not reduce the risk of complications compared with that of definitive surgery.ConclusionThe 30-day and 90-day postoperative mortality rates were significantly reduced over the time of the study. Age and ASA score were risk factors for severe postoperative complications.
Project description:PurposeColorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia.MethodsThis case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs.ResultsThere were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98-3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia.ConclusionsOur results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal.
Project description:PurposeBRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia.MethodsStudy subjects included Kaiser Permanente Washington members aged 20-75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers.ResultsWe included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06-20.51).ConclusionOur results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.
Project description:BackgroundIncreasing evidence suggests that conventional adenomas (CAs) and serrated polyps (SPs) represent two distinct groups of precursor lesions for colorectal cancer (CRC). The influence of common genetic variants on risk of CAs and SPs remain largely unknown.MethodsAmong 27 426 participants within three prospective cohort studies, we created a weighted genetic risk score (GRS) based on 40 CRC-related single nucleotide polymorphisms (SNPs) identified in previous genome-wide association studies; and we examined the association of GRS (per one standard deviation increment) with risk of CAs, SPs and synchronous CAs and SPs, by multivariable logistic regression. We also analysed individual variants in the secondary analysis.ResultsDuring 18-20 years of follow-up, we documented 2952 CAs, 1585 SPs and 794 synchronous CAs and SPs. Higher GRS was associated with increased risk of CAs [odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.12-1.21] and SPs (OR = 1.09, 95% CI: 1.03-1.14), with a stronger association for CAs than SPs (Pheterogeneity=0.01). An even stronger association was found for patients with synchronous CAs and SPs (OR = 1.32), advanced CAs (OR = 1.22) and multiple CAs (OR = 1.25). Different sets of variants were associated with CAs and SPs, with a Spearman correlation coefficient of 0.02 between the ORs associating the 40 SNPs with the two lesions. After correcting for multiple testing, three variants were associated with CAs (rs3802842, rs6983267 and rs7136702) and two with SPs (rs16892766 and rs4779584).ConclusionsCommon genetic variants play a potential role in the conventional and serrated pathways of CRC. Different sets of variants are identified for the two pathways, further supporting the aetiological heterogeneity of CRC.
Project description:The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (<138 ng/mL), those with circulating 27-OHC at or above the fourth quartile (≥201 ng/mL) had 24% higher risk of adenomas (RR, 1.24; 95% CI, 1.05-1.47) and 89% higher risk of advanced adenomas (RR, 1.89; 95% CI, 1.17-3.06). Stronger associations were observed among participants with advanced adenomas at baseline. Circulating 27-OHC was not associated with risk of hyperplastic polyps (RR, 0.90; 95% CI, 0.66-1.22) or sessile serrated adenomas/polyps (RR, 1.02; 95% CI, 0.50-2.07). Circulating 27-OHC may be a risk factor for colorectal adenomas but not serrated polyps. PREVENTION RELEVANCE: This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.