Pouch-Related Symptoms and Quality of Life in Patients with Ileal Pouch-Anal Anastomosis

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the standard surgical treatment for the majority of patients with inflammatory bowel disease (IBD) who require colectomy. We evaluated the prevalence of pouch-related symptoms among the Crohn's and Colitis Foundation of America Partners cohort and the effect of pouch-related symptoms on Patient-Reported Outcome Measurement Information System measures. Methods: We performed analyses nested in the Crohn's and Colitis Foundation of America Partners cohort. We used bivariate analyses to compare demographics and medication use among patients with ulcerative colitis or indeterminate colitis and pouch-related symptoms and those with IPAA without symptoms. We also compared Patient-Reported Outcome Measurement Information System domains (measured in T-scores) and short IBD questionnaire quality of life scales between symptomatic pouch patients (over the past 6 mo) and those without symptoms. Results: Among 243 patients reporting a history of IPAA, 199 (82%) reported a history of pouch symptoms. Patients with recent pouch symptoms demonstrated higher mean T-scores in pain interference (53.0 versus 45.3; P < 0.001), depression (51.0 versus 46.4; P = 0.002), and fatigue (56.3 versus 47.0; P < 0.001). Symptomatic pouch patients reported lower mean scores in social role satisfaction (47.4 versus 54.6) and short IBD questionnaire (4.8 versus 5.8) (both P < 0.001). These differences were all clinically meaningful. Conclusions: In a large sample of patients with IBD, nearly all patients with IPAA reported a history of pouch symptoms. Patients experiencing symptoms within the 6 months before the survey assessment demonstrated clinically meaningful decrements in patient-reported outcomes in multiple domains of physical and psychosocial functioning

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer

Targeted therapies in small cell lung cancer: A review

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is characterized by a rapid doubling time, early onset of dissemination and high sensitivity to chemotherapy. Despite the potential for cure in patients with limited disease with concurrent chemoradiation and an initial good response to chemotherapy in extensive disease, there is a high chance of disease relapse with an overall poor median survival for both stages. With increasing translational research and a better understanding of the molecular basis of cancer, a number of molecular targets have been identified in various preclinical studies. This review summarizes potentially viable targets and new agents that have been developed and employed in recent, ongoing and future clinical trials to attempt to improve clinical outcomes in this disease

Male breast cancer

The earliest reference to breast cancer (BC) in men dates from 3000-2500 BCE, on an Egyptian papyrus [11], and the first clinical report was described in the 14th century by John of Arderne [71]. Carcinoma of the male breast is a relatively rare disease that accounts for less than 1% of all cases of cancer in men. Therefore, BC in men has largely taken a back seat to the worldwide effort to control this disease in women. Similarly, the literature regarding male BC consists mainly of case-control and retrospective studies involving small numbers of patients [28]. The statistical accuracy of the clinical characteristics of male BC is not fully established and knowledge relevant to specific aspects of the disease in men is still limited. Consequently, treatment strategies have been largely guided by extrapolation from experience in women. In this chapter, the available information on risk, prognostic factors, clinical features, and treatment modalities of male BC has been summarized. Tailored prospective clinical trials in this disease, through large Intergroup networks, should be initiated. © Springer-Verlag Berlin Heidelberg 2006.SCOPUS: ch.binfo:eu-repo/semantics/publishe

Rare germline copy number variants (CNVs) and breast cancer risk

Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs.Genome Instability and Cance