Surveillance Imaging with PET/CT and CT and/or MRI for Head and Neck Cancer and Mortality: A Population-based Study.

Background To the knowledge of the authors, no strong evidence supports surveillance imaging in patients with head and neck cancer (HNC). Purpose To investigate the association between surveillance imaging and mortality using a population-based study design with statewide cancer registry data, all-payer claims data, and health care facility data. Materials and Methods The retrospective population-based study identified patients with HNC diagnosed between January 2012 and December 2017. Current Procedural Terminology codes were used to search surveillance imaging procedures. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for mortality with adjustment for sex, ethnicity, age, health insurance status, cancer site, stage, and treatment. Results The study identified 1004 patients (mean age, 61 years ± 12 [SD]; 753 men), including 902 patients with squamous cell carcinoma (SCC) HNC and 102 patients with non-SCC. The effect of imaging on mortality among patients with SCC was not statistically significant when the entire sample was analyzed (HR, 0.76; 95% CI: 0.57, 1.02; P = .07). However, in stratified analyses by cancer stage, surveillance imaging was associated with lower mortality among patients with SCC for regionalized cancer stage (HR, 0.55; 95% CI: 0.36, 0.83; P = .005) and distant cancer stage (HR, 0.40; 95% CI: 0.19, 0.83; P = .01). Among patients with non-SCC, surveillance imaging was associated with lower mortality versus no surveillance imaging (HR, 0.19; 95% CI: 0.04, 0.94; P = .04). PET/CT was associated with lower mortality for patients with SCC (HR, 0.29; 95% CI: 0.09, 0.94; P = .04), and CT and/or MRI was associated with lower mortality for patients with non-SCC (HR, 0.11; 95% CI: 0.01, 0.94; P = .04). Conclusion Surveillance imaging was associated with lower mortality among patients with head and neck squamous cell carcinoma with regionalized or distant disease. The surveillance imaging protective association was observed up to 2 years after treatment completion. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Branstetter in this issue.

Contributions of cancer treatment, comorbidities, and obesity to aging-related disease risks among non-Hodgkin lymphoma survivors.

PURPOSE: It is unknown whether cancer treatment contributes more to long-term disease risk than lifestyle factors and comorbidities among B-cell non-Hodgkin lymphoma (B-NHL) survivors. METHODS: B-NHL survivors were identified in the Utah Cancer Registry from 1997 to 2015. Population attributable fractions (PAF) were calculated to assess the role of clinical and lifestyle factors for six cardiovascular, pulmonary, and renal diseases. RESULTS: Cancer treatment contributed to 11% of heart and pulmonary conditions and 14.1% of chronic kidney disease. Charlson Comorbidity Index (CCI) at baseline contributed to all six diseases with a range of 9.9% of heart disease to 26.5% of chronic kidney disease. High BMI at baseline contributed to 18.4% of congestive heart failure and 7.9% of pneumonia, while smoking contributed to 4.8% of COPD risk. CONCLUSION: Cancer treatment contributed more to heart disease, COPD, and chronic kidney disease than lifestyle factors and comorbidities among B-NHL survivors. High BMI at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, whereas smoking at baseline was not a major contributor in this B-NHL survivor cohort. Baseline comorbidities consistently demonstrated high attributable risks for these diseases, demonstrating a strong association between preexisting comorbidities and aging-related disease risks.

Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study.

BACKGROUND: Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. METHODS: A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. RESULTS: Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. CONCLUSION: Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.

Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.

Sexual dysfunction among gynecologic cancer survivors in a population-based cohort study.

Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HRRegional vs. Localized: 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.

A role for the MEGF6 gene in predisposition to osteoporosis.

Osteoporosis is a common skeletal disorder characterized by deterioration of bone tissue. The set of genetic factors contributing to osteoporosis is not completely specified. High-risk osteoporosis pedigrees were analyzed to identify genes that may confer susceptibility to disease. Candidate predisposition variants were identified initially by whole exome sequencing of affected-relative pairs, approximately cousins, from 10 pedigrees. Variants were filtered on the basis of population frequency, concordance between pairs of cousins, affecting a gene associated with osteoporosis, and likelihood to have functionally damaging, pathogenic consequences. Subsequently, variants were tested for segregation in 68 additional relatives of the index carriers. A rare variant in MEGF6 (rs755467862) showed strong evidence of segregation with the disease phenotype. Predicted protein folding indicated the variant (Cys200Tyr) may disrupt structure of an EGF-like calcium-binding domain of MEGF6. Functional analyses demonstrated that complete loss of the paralogous genes megf6a and megf6b in zebrafish resulted in significant delay of cartilage and bone formation. Segregation analyses, in silico protein structure modeling, and functional assays support a role for MEGF6 in predisposition to osteoporosis.

Adverse respiratory outcomes among head and neck cancer survivors in the Utah Cancer Survivors Study.

BACKGROUND: The number of head and neck cancer (HNC) survivors has been increasing because of improving survival in the United States. The aim of this study was to evaluate the incidence of respiratory disease diagnoses in HNC survivors in comparison with cancer-free individuals. A second aim was to investigate risk factors for respiratory disease among HNC survivors. METHODS: Patients with HNC diagnosed from 1996 to 2012 were identified in the Utah Cancer Registry (n = 1901). Up to 5 cancer-free individuals from the general population (n = 7796) were matched to each HNC survivor by birth year, sex, birth state, and follow-up time. Electronic medical records and statewide health care facility data were used to identify a disease diagnosis after the cancer diagnosis. Cox proportional hazards models were used to estimate the risks of respiratory diseases. RESULTS: The median follow-up times were 4.5 years for HNC survivors and 7.8 years for the general population cohort. The risks of respiratory infection (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.40-1.90), chronic obstructive pulmonary diseases and bronchiectasis (HR, 2.65; 95% CI, 2.13-3.29), and aspiration pneumonitis (HR, 6.21; 95% CI, 3.98-9.68) were higher among HNC survivors than the general population cohort more than 5 years after the cancer diagnosis. Age at diagnosis, baseline body mass index, sex, baseline smoking status, treatment modality, primary site, and stage were associated with the risk of adverse respiratory outcomes among HNC survivors. CONCLUSIONS: The risk of adverse respiratory outcomes was much higher among HNC survivors than the general population cohort. Multidisciplinary care is needed to prevent the occurrence of adverse respiratory outcomes among HNC survivors.

Rural-urban disparities in colorectal cancer survival and risk among men in Utah: a statewide population-based study.

Rural areas of the U.S. experience disproportionate colorectal cancer (CRC) death compared to urban areas. The authors aimed to analyze differences in CRC survival between rural and urban Utah men and investigate potential prognostic factors for survival among these men. A cohort of Utah men diagnosed with CRC between 1997 and 2013 was identified from the Utah Cancer Registry. Survival and prognostic factors were analyzed via 5-year CRC survival and Cox proportional hazards models, stratified by rural/urban residence. Among 4,660 men diagnosed with CRC, 15.3% were living in rural Utah. Compared with urban men, rural CRC patients were diagnosed at older ages and in different anatomic subsites; more were overweight, and current smokers. Differences in stage and treatment were not apparent between rural and urban CRC patients. Compared with urban counterparts, rural men experienced a lower CRC survival (Hazard Ratio 0.55, 95% CI 0.53, 0.58 vs. 0.58, 95% CI 0.56, 0.59). Race and cancer treatment influenced CRC survival among men living in both urban and rural areas. Factors of CRC survival varied greatly among urban and rural men in Utah. The influence of social and environmental conditions on health behaviors and outcomes merits further exploration.

Genitourinary disease risks among ovarian cancer survivors in a population-based cohort study.

OBJECTIVE: While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. METHODS: We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. RESULTS: Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. CONCLUSIONS: Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.

Long-term diabetes risk among endometrial cancer survivors in a population-based cohort study.

OBJECTIVE: The majority of endometrial cancer patients are overweight or obese at cancer diagnosis. Obesity is a shared risk factor for both endometrial cancer and diabetes, but it is unknown whether endometrial cancer patients have increased diabetes risks. The aim of our study was to investigate diabetes risk among endometrial cancer patients. METHODS: Endometrial cancer patients diagnosed between 1997 and 2012 in Utah (n = 2,314) were identified. Women from the general population (n = 8,583) were matched to the cancer patients on birth year and birth state. Diabetes diagnoses were identified from electronic medical records and statewide healthcare facility databases. Cox proportional hazards models were used to estimate hazard ratios for diabetes after cancer diagnosis. RESULTS: Endometrial cancer survivors had a significantly higher risk of type II diabetes when compared to women from the general population in the first year after cancer diagnosis (HR = 5.22, 95% CI = 4.05, 6.71), >1-5 years after cancer diagnosis (HR = 1.67, 95% CI = 1.31, 2.12), and >5 years after cancer diagnosis (HR = 1.65, 95% CI = 1.29, 2.11). Endometrial cancer patients who were obese at cancer diagnosis had a three-fold increase in type II diabetes risk (HR = 2.99, 95%CI = 2.59, 3.45). Although endometrial cancer patients diagnosed at distant stage had a higher risk of diabetes, cancer treatment did not appear to contribute to any diabetes risks. CONCLUSIONS: In conclusion, endometrial cancer survivors had a higher risk of diabetes than women in the general population. These results suggest that long term monitoring for diabetes is indicated for endometrial cancer survivors.

Risk of pelvic organ prolapse treatment based on extended family history.

BACKGROUND: Family history of pelvic organ prolapse among first-degree relatives is an established risk factor for pelvic organ prolapse; however, consideration of the constellation of family history that extends to distant relationships allows for more accurate determination of risk and may improve pelvic organ prolapse risk prediction estimates. OBJECTIVE: The purpose of this study was to assess risk for pelvic organ prolapse treatment based on varying family histories of pelvic organ prolapse and included number and types of affected relatives, ages of relatives at pelvic organ prolapse treatment, and whether the family history is of maternal or paternal origin. STUDY DESIGN: This was a retrospective, population-based study that involved the Utah Population Database, which is a population resource that includes extensive genealogy information linked to medical records. The study population included 453,522 total women: 4628 women with a diagnosis of treated (surgical or pessary) pelvic organ prolapse and their 15,530 first-degree relatives; 33,782 second-degree relatives, and 66,469 third-degree relatives. We estimated relative risk of treated pelvic organ prolapse based on specific family history constellations. RESULTS: Relative risk estimates increased with a family history of increasing numbers of treated first-degree relatives with pelvic organ prolapse (first-degree relatives, ≥1 [relative risk, 2.36; 95% confidence interval, 2.15-2.58], first-degree relatives, ≥2 [relative risk, 3.79; 95% confidence interval, 2.65-5.24], and first-degree relatives, ≥3 [relative risk, 6.26; 95% confidence interval, 1.29-18.30]). Having a family history of ≥3 affected third-degree relatives (eg, first cousins) and no affected first- or second-degree relatives was similar in risk to having 1 affected first-degree relative. Relative risk estimates decreased with increasing age of treatment for first-degree family members. Risks in individuals with a positive maternal family history for pelvic organ prolapse were consistently higher than risks in individuals with equivalent paternal family history, but paternal inheritance still played a role. Approximately 4% of the total studied female population was found to have a >2-fold risk of being treated for pelvic organ prolapse and is considered high-risk based on their family history. CONCLUSION: We provide estimates for treated pelvic organ prolapse based on an extensive family history of pelvic organ prolapse using a large population-based sample. Risk for treated pelvic organ prolapse increased with increasing numbers of affected close and distant female relatives, earlier age of pelvic organ prolapse treatment in relatives, and maternal inheritance. These risk estimates may be useful for genetic studies and investigation of risk reduction strategies in those at highest risk for pelvic organ prolapse.

Clinical and Molecular Features of Post-Colonoscopy Colorectal Cancers.

BACKGROUND & AIMS: Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6-60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy). METHODS: Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC. Archived specimens were retrieved and tested for microsatellite instability (MSI), CpG island methylation, and mutations in KRAS and BRAF. There were 2659 cases of CRC diagnosed within the study window; 6% of these (n = 159) were defined as PCCRCs; 84 of these cases had tissue available and were matched to 84 subjects with detected CRC. RESULTS: Higher proportions of PCCRCs than detected CRCs formed in the proximal colon (64% vs 44%; P = .016) and were of an early stage (86% vs 69%; P = .040). MSI was observed in 32% of PCCRCs compared with 13% of detected CRCs (P = .005). The other molecular features were found in similar proportions of PCCRCs and detected CRCs. In a multivariable logistic regression, MSI (odds ratio, 4.20; 95% CI, 1.58-11.14) was associated with PCCRC. There was no difference in 5-year survival between patients with PCCRCs vs detected CRCs. CONCLUSION: In this population-based cross-sectional study of incident CRC cases in Utah, we found PCCRCs to be more likely to arise in the proximal colon and demonstrate MSI, so PCCRCs and detected CRC appear to have different features or processes of tumorigenesis. Additional studies are needed to determine if post-colonoscopy cancers arise through a specific genetic pathway.

Family History Associates With Increased Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing colorectal cancer (CRC). Although family history of CRC is a well-established risk factor in healthy individuals, its role in patients with IBD is less clear. We aimed to estimate the risk of CRC in a cohort of patients with IBD from Utah and the significance of family history of CRC in a first-degree relative (FDR). METHODS: We identified Utah residents with IBD, using the Intermountain Healthcare and University of Utah Health Sciences databases, from January 1, 1996, through December 31, 2011. CRCs were identified using the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. CRC incidence was compared with that of the state population by standardized incidence ratios (SIRs). RESULTS: A cohort of 9505 individuals with IBD was identified and 101 developed CRC during the study period. The SIR for CRC in patients with Crohn's disease was 3.4 (95% CI, 2.3-4.4), and in patients with ulcerative colitis was 5.2 (95% CI, 3.9-6.6). Patients with IBD and a concurrent diagnosis of primary sclerosing cholangitis had the greatest risk of CRC (SIR, 14.8; 95% CI, 8.3-21.2). A history of CRC in a FDR was associated with a nearly 8-fold increase in risk of CRC in patients with IBD (SIR, 7.9; 95% CI, 1.6-14.3), compared with the state population. CONCLUSIONS: Patients with IBD have a 3- to 5-fold increase in risk of CRC, and those with CRC in a FDR have an almost 8-fold increase in risk. Family history may act as a simple measure to identify individuals with IBD at highest risk for CRC and indicates the need for enhanced surveillance in this population.

Prognostic factors for rural endometrial cancer patients in a population-based cohort.

BACKGROUND: Endometrial cancer is the second most common cancer among female cancer survivors in the US and is increasing in incidence. Rural endometrial cancer patients experience lower survival rates but the reasons for the lower survival are not known. The aim of this study is to examine whether prognostic factors are different for rural and urban patients in a population-based cohort. METHODS: Endometrial cancer patients diagnosed 1997-2012 were identified through the Utah Cancer Registry and Utah Population Database. The address at cancer diagnosis was used to classify patients in rural or urban residences. Demographic and cancer-specific characteristics were examined as prognostic factors for both all-cause and endometrial cancer-specific mortality using Cox proportional hazards models. RESULTS: There were 2,994 endometrial cancer patients and 14.1% of these patients lived in rural areas at diagnosis. Rural endometrial cancer patients were older at cancer diagnosis and did not appear to be different in terms of obesity or overweight at cancer diagnosis. There were no differences for treatment or stage at diagnosis although rural patients had higher proportions of higher grade. Age at diagnosis, poverty, education, and histology were significant prognostic factors for all-cause death. Rural patients with more advanced stages of cancer had significantly increased risks of all-cause and endometrial cancer-specific death than urban patients. Rural endometrial cancer patients diagnosed at advanced stage had a 17-fold increase in the risk of all-cause death compared to an 8-fold increase in death for urban patients. CONCLUSIONS: Rural endometrial cancer patients in Utah were older at diagnosis, had higher grade and higher comorbidities. While urban and rural endometrial cancer patients shared many prognostic factors, the risk of mortality is greater among rural patients with advanced stage endometrial cancer. Future studies should examine where patients are receiving treatment and how that impacts their survival and how to reduce the mortality rates of high risk patients.

Significant Linkage Evidence for Interstitial Cystitis/Painful Bladder Syndrome on Chromosome 3.

PURPOSE: Interstitial cystitis/painful bladder syndrome is a chronic pelvic pain condition of unknown etiology. We hypothesized that related interstitial cystitis/painful bladder syndrome cases were more likely to have a genetic etiology. The purpose of this study was to perform a genetic linkage analysis. MATERIALS AND METHODS: We identified interstitial cystitis/painful bladder syndrome cases using diagnostic codes linked to the Utah Population Database genealogy resource and to electronic medical records. For this analysis we used 13 high risk pedigrees, defined as having a statistical excess number of interstitial cystitis/painful bladder syndrome cases among descendants compared to matched hospital population rates. Case status was confirmed in medical records using natural language processing. DNA was obtained from stored, nonneoplastic, formalin fixed, paraffin embedded tissue blocks. Each pedigree had at least 2 cases with DNA available. Parametric linkage analysis was performed. RESULTS: Pedigrees ranged in size from 2 to 12 genotyped cases for a total of 48 cases. Significant genome wide linkage evidence was found under a dominant model on chromosome 3p13-p12.3 (maximum heterogeneity θ logarithm of odds 3.56). Two pedigrees showed at least nominal linkage evidence in this region (logarithm of odds greater than 0.59). The most informative pedigree included 12 interstitial cystitis/painful bladder syndrome cases (pedigree θ logarithm of odds 2.1). Other regions with suggestive linkage evidence included 1p21-q25, 3p21.1-p14.3, 4q12-q13, 9p24-p22 and 14q24-q31, all under a dominant model. CONCLUSIONS: While the etiology of interstitial cystitis/painful bladder syndrome is unknown, this study provides evidence that a genetic variant(s) on chromosome 3 and possibly on chromosomes 1, 4, 9 and 14 contribute to an interstitial cystitis/painful bladder syndrome predisposition. Sequence analysis of affected cases in identified pedigrees may provide insight into genes contributing to interstitial cystitis/painful bladder syndrome.

Long-term, adverse genitourinary outcomes among endometrial cancer survivors in a large, population-based cohort study.

OBJECTIVE: With the increasing incidence of endometrial cancer, the high survival rate, and the large number of endometrial cancer survivors, investigations of long-term genitourinary outcomes are important for the management of these outcomes among endometrial cancer survivors. METHODS: Cohorts of 2648 endometrial cancer survivors diagnosed in the state of Utah between 1997 and 2012 and 10,503 general population women were identified. All ICD-9 diagnosis codes were collected from the state's two largest healthcare systems and statewide databases. Multivariate Cox regression models were used to estimate hazard ratios at 1-5years and >5-10years after endometrial cancer diagnosis for genitourinary outcomes. RESULTS: Endometrial cancer survivors were at elevated risk for urinary system disorders between 1 and 5years (HR: 1.64, 95% CI: 1.50-1.78) and >5-10years (HR: 1.40, 95% CI: 1.26-1.56) and genital organ disorders between 1 and 5years (HR: 1.71, 95% CI: 1.58-2.03) and >5-10years (HR: 1.33, 95% CI: 1.19-1.49). Significantly elevated risk was observed among endometrial cancer survivors for renal failure, chronic kidney disease, urinary tract infections, and nonmalignant breast conditions, persisting between >5-10years. Between 1 and 5years after cancer diagnosis, those with higher stage, higher grade, older age and treated with radiation or chemotherapy were at higher risk for urinary disorders. CONCLUSIONS: Endometrial cancer survivors were at higher risk for many genitourinary outcomes compared to women from the general population. This study presents evidence suggesting the necessity of increased monitoring and counseling for genitourinary disorders for endometrial cancer patients both immediately after treatment cessation and for years afterwards.

Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah.

BACKGROUND AND AIMS: The molecular, endoscopic, and histological features of IBD-associated CRC differ from sporadic CRC. The objective of this study was to describe the prevalence, clinical features, and prognosis of IBD-associated CRC compared to patients with sporadic CRC in a US statewide population-based cohort. METHODS: All newly diagnosed cases of CRC between 1996 and 2011 were obtained from Utah Cancer Registry. IBD was identified using a previously validated algorithm, from statewide databases of Intermountain Healthcare, University of Utah Health Sciences, and the Utah Population Database. Logistic regression was performed to identify risk factors associated with IBD-associated cancer and Cox regression for differences in survival. RESULTS: Among 12,578 patients diagnosed with CRC, 101 (0.8%) had a prior history of IBD (61 ulcerative colitis and 40 Crohn's disease). The mean age at CRC diagnosis was greater for patients without IBD than those with IBD (67.1 vs 52.8 years, P < 0.001). Individuals with IBD-associated CRC were more likely to be men (odds ratio [OR] 1.90, 95% CI 1.23-2.92), aged less than 65 years (OR 6.77, 95% CI 4.06-11.27), and have CRC located in the proximal colon (OR 2.79, 95% CI 1.85-4.20) than those with sporadic CRC. Nearly 20% of the IBD-associated CRCs had evidence of primary sclerosing cholangitis. After adjustment for age, gender, and stage at diagnosis, the excess hazard of death after CRC diagnosis was 1.7 times higher in IBD than in non-IBD patients (95% CI 1.27-2.33). CONCLUSIONS: The features of patients with CRC and IBD differ significantly from those without IBD and may be associated with increased mortality.

Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah.

BACKGROUND & AIMS: Colorectal cancer (CRC) frequently develops in multiple members of the same families, but more data are needed to prepare effective screening guidelines. We quantified the risk of CRC and adenomas in first-degree relatives (FDRs) and second-degree relatives and first cousins of individuals with CRC, and stratified risk based on age at cancer diagnosis. METHODS: We performed a case-control study of Utah residents, 50-80 years old, who underwent colonoscopy from 1995 through 2009. Index cases (exposed to colonoscopy) were colonoscopy patients with a CRC diagnosis. Age- and sex-matched individuals, unexposed to colonoscopy (controls) were selected to form the comparison groups for determining risk in relatives. Colonoscopy results were linked to cancer and pedigree information from the Utah Population Database to investigate familial aggregation of colorectal neoplasia using Cox regression analysis. RESULTS: Of 126,936 patients who underwent a colonoscopy, 3804 were diagnosed with CRC and defined the index cases. FDRs had an increased risk of CRC (hazard rate ratio [HRR], 1.79; 95% confidence interval [CI],1.59-2.03), as did second-degree relatives (HRR, 1.32; 95% CI, 1.19-1.47) and first cousins (HRR, 1.15; 95% CI, 1.07-1.25), compared with relatives of controls. This risk was greater for FDRs when index patients developed CRC at younger than age 60 years (HRR, 2.11; 95% CI, 1.70-2.63), compared with older than age 60 years (HRR, 1.77; 95% CI, 1.58-1.99). The risk of adenomas (HRR, 1.82; 95% CI, 1.66-2.00) and adenomas with villous histology (HRR, 2.43; 95% CI, 1.96-3.01) also were increased in FDRs. Three percent of CRCs in FDRs would have been missed if the current guidelines, which stratify screening recommendations by the age of the proband, were strictly followed. CONCLUSIONS: FDRs, second-degree relatives, and first cousins of patients who undergo colonoscopy and are found to have CRC have a significant increase in the risk of colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and families.

Characteristics of missed or interval colorectal cancer and patient survival: a population-based study.

BACKGROUND & AIMS: Colorectal cancers (CRCs) diagnosed within a few years after an index colonoscopy can arise from missed lesions or the development of a new tumor. We investigated the proportion, characteristics, and factors that predict interval CRCs that develop within 6-60 months of colonoscopy. METHODS: We performed a population-based cohort study of Utah residents who underwent colonoscopy examinations from 1995 through 2009 at Intermountain Healthcare or the University of Utah Health System, which provide care to more than 85% of state residents. Colonoscopy results were linked with cancer histories from the Utah Population Database to identify patients who underwent colonoscopy 6-60 months before a diagnosis of CRC (interval cancer). Logistic regression was performed to identify risk factors associated with interval cancers. RESULTS: Of 126,851 patients who underwent colonoscopies, 2659 were diagnosed with CRC; 6% of these CRCs (159 of 2659) developed within 6 to 60 months of a colonoscopy. Sex and age were not associated with interval CRCs. A higher percentage of patients with interval CRC were found to have adenomas at their index colonoscopy (57.2%), compared with patients found to have CRC detected at colonoscopy (36%) or patients who did not develop cancer (26%) (P < .001). Interval CRCs tended to be earlier-stage tumors than those detected at index colonoscopy, and to be proximally located (odds ratio, 2.24; P < .001). Patients with interval CRC were more likely to have a family history of CRC (odds ratio, 2.27; P = .008) and had a lower risk of death than patients found to have CRC at their index colonoscopy (hazard ratio, 0.63; P < .001). CONCLUSIONS: In a population-based study in Utah, 6% of all patients with CRC had interval cancers (cancer that developed within 6 to 60 months of a colonoscopy). Interval CRCs were associated with the proximal colon, earlier-stage cancer, lower risk of death, higher rate of adenoma, and family history of CRC. These findings indicate that interval colorectal tumors may arise as the result of distinct biologic features and/or suboptimal management of polyps at colonoscopy.

Risk of colorectal cancer and adenomas in the families of patients with adenomas: a population-based study in Utah.

BACKGROUND: Guidelines recommend that individuals with a first-degree relative (FDR) diagnosed with colorectal cancer (CRC) or advanced adenoma before age 60 years should undergo colonoscopy starting at age 40 years. The authors quantified the risk of adenomas and CRC in FDRs, second-degree relatives (SDRs), and third-degree relatives (TDRs) of patients diagnosed with adenomas and advanced adenomas. METHODS: A population-based, retrospective, case-control study was performed of residents of the state of Utah aged 50 years to 80 years who underwent colonoscopy between 1995 and 2009 at Intermountain Healthcare or the University of Utah. Controls were selected from the population of colonoscopy patients who were free of adenomas or CRC and matched to each case based on sex and birth year. Colonoscopy results were linked with cancer and pedigree information from the Utah Population Database to investigate the familial aggregation of adenomas and CRC using Cox regression analysis. The unit of analysis was the relatives of cases and controls. RESULTS: Of 126,936 patients who underwent colonoscopy, 43,189 had adenomas and 5563 had advanced adenomas and defined the case population. An elevated risk of CRC was found in FDRs (relative risk [RR], 1.35; 95% confidence interval [95% CI], 1.25-1.46), SDRs (RR, 1.15; 95% CI, 1.07-1.23) of adenoma cases, and in FDRs of advanced adenoma cases (RR, 1.68; 95% CI, 1.29-2.18) compared with controls. Approximately 10% of CRCs diagnosed in relatives would have been missed if the current screening guidelines were strictly adhered to. CONCLUSIONS: Relatives of colonoscopy patients with adenomas and advanced adenomas appear to have a significantly elevated risk of developing colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and their families.