6 research outputs found
Head-and-neck paragangliomas are associated with sleep-related complaints, especially in the presence of carotid body tumors
Item does not contain fulltextOBJECTIVES: The carotid body functions as a chemoreceptor. We hypothesized that head-and-neck paragangliomas (HNP) may disturb the function of these peripheral chemoreceptors and play a role in sleep-disordered breathing. DESIGN: This is a case-control study. SETTING: This study was conducted in a tertiary referral center. PARTICIPANTS AND MAIN OUTCOME MEASURES: We assessed fatigue, sleep, and exercise capacity in 74 HNP patients using three questionnaires (Epworth Sleepiness Scale, St. George Respiratory Questionnaire, and a standard clinical sleep assessment questionnaire). Outcomes were compared to those of age- and sex-matched controls. RESULTS AND CONCLUSIONS: Activity, disturbance of psychosocial function, and total score were worse compared to controls (15.4 +/- 18.5 vs. 7.2 +/- 9.9, P = 0.007; 5.3 +/- 10.5 vs. 1.2 +/- 2.6, P = 0.008; and 10.4 +/- 12.9 vs. 5.0 +/- 4.8, P = 0.006, respectively). Patients reported more daytime fatigue, concentration difficulties, and depression (51% vs. 24%, P = 0.006; 31% vs. 10%, P = 0.010; and 19% vs. 2%, P = 0.012). Waking up was reported to be less refreshing in HNP patients (53% vs. 73%, P = 0.038). Dysphonia was a predictor of symptoms, activity, disturbance of psychosocial function, and total scores. Remarkably, the presence of a carotid body tumor was an independent predictor of increased daytime sleepiness (beta = 0.287, P = 0.029). In conclusion, patients with HNP have remarkable sleep-related complaints. Especially the presence of carotid body tumors appears to be associated with increased daytime somnolence.1 juni 201
Psychological distress and use of psychosocial support in familial adenomatous polyposis
OBJECTIVE: Familial adenomatous polyposis (FAP) is characterized by multiple adenomas in the colorectum with a high risk to develop colorectal cancer. It is unclear whether individuals at risk of FAP experience distress due to this potentially life-threatening disease. This nationwide study assessed: (1) the prevalence of psychological distress; and (2) the need for and use of specialized professional psychosocial support. METHODS: In this cross-sectional study, all individuals from families at high risk for FAP registered at the Netherlands Foundation for the Detection of Hereditary Tumours were invited to complete a questionnaire assessing, among other issues, generalized, cancer-specific and FAP-specific distress. RESULTS: In total, 525 individuals completed the questionnaire. Approximately 20% of the respondents had moderate to severe levels of FAP-specific distress. Levels of generalized distress were comparable to the general Dutch population. Significantly more individuals with a FAP diagnosis had frequent cancer worries than those at risk of FAP or non-carriers (p=0.02). Distress levels were more strongly associated with psychosocial variables (e.g. perceived cancer risk), than with sociodemographic or clinical variables. Up to 43% of the variance in distress could be explained by all variables combined. Of those moderately to severely distressed, 26% had received specialized professional psychosocial support, while 30% of those did not receive the support they wanted. CONCLUSIONS: A substantial minority of individuals reported moderate to severe distress levels associated with FAP. However, only one-third of those received specialized professional psychosocial support. We recommend the use of a screening questionnaire to identify individuals in need of such suppor
Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer
Immunohistochemistry (IHC) and microsatellite instability (MSI) analysis can be used to identify patients with a possible DNA mismatch repair defect [hereditary nonpolyposis colorectal carcinoma (HNPCC)]. The Bethesda criteria have been proposed to select families for determination of MSI. The aims of this study were to assess the yield of MSI analysis in families suspected for HNPCC, to compare the results of immunohistochemical staining and MSI analysis, and to assess the additional value of PMS2 staining. Clinical data and tumors were collected from 725 individuals from 631 families with suspected HNPCC. MSI analysis was performed using eight markers including the 5 National Cancer Institute markers. Four immunohistochemical staining antibodies were used (MLH1, MSH2, MSH6 and PMS2). A MSI-H (tumors with instability for >30% of the markers) phenotype in colorectal cancers (CRCs) was observed in 21-49% of families that met the various Bethesda criteria. In families with three cases of CRC diagnosed at age > 50 years, families with a solitary case of CRC diagnosed between ages 45 and 50 years, and families with one CRC case and a first-degree relative with a HNPCC-related cancer, one diagnosed between ages 45 and 50 years (all Bethesda-negative families), the yield of MSI-H was 10-26%. Immunohistochemical staining confirmed the MSI results in 93% of the cases. With IHC, adding PMS2 staining led to the identification of an additional 23% of subjects with an hMLH1 germ-line mutation (35 carriers were tested). The Bethesda guidelines for MSI analysis should include families with three or more cases of CRC diagnosed at age > 50 years. The age at diagnosis of CRC in the original guidelines should be raised to 50 years. Routine IHC diagnostics for HNPCC should include PMS2 stainin
Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers
Background: Germline mutations in MSH6 account for 10%–20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain. Methods: We identified 113 families of MSH6 mutation carriers from five countries that we ascertained through family cancer clinics and population-based cancer registries. Mutation status, sex, age, and histories of cancer, polypectomy, and hysterectomy were sought from 3104 of their relatives. Age-specific cumulative risks for carriers and hazard ratios (HRs) for cancer risks of carriers, compared with those of the general population of the same country, were estimated by use of a modified segregation analysis with appropriate conditioning depending on ascertainment. Results: For MSH6 mutation carriers, the estimated cumulative risks to ages 70 and 80 years, respectively, were as follows: for colorectal cancer, 22% (95% confidence interval [CI] = 14% to 32%) and 44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%) and 20% (95% CI = 11% to 35%) for women; for endometrial cancer, 26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); and for any cancer associated with Lynch syndrome, 24% (95% CI = 16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95% CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Compared with incidence for the general population, MSH6 mutation carriers had an eightfold increased incidence of colorectal cancer (HR = 7.6, 95% CI = 5.4 to 10.8), which was independent of sex and age. Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7) and a sixfold increased incidence of other cancers associated with Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7). Conclusion: We have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers.Laura Baglietto... Dutch Lynch Syndrome Study Group... Graeme Suthers... et al