Female Circumcision

It\u27s easy for us to be self-righteous and rant about the cruelty of female circumcision. However, people in first world countries are often just as destructive, if not more so, to their bodies

A retrospective cohort study of the influence of lifestyle factors on survival of patients undergoing surgery for colorectal cancer.

Aim: Several modifiable and non-modifiable health related behaviours are associated with the incidence of Colorectal Cancer (CRC), but there is little research on their association with survival. The project aimed to investigate possible relationships between modifiable behavioural factors and outcomes on a study cohort of CRC patients undergoing potentially curative surgery. Method: A retrospective cohort study was carried out of patients diagnosed with non-metastatic CRC undergoing elective curative surgery (January 2011 - December 2012), residing in the NHS Greater Glasgow & Clyde (NHSGGC) area, UK. Data were obtained from the Scottish Cancer Registry, National Scottish Death Records. Pre-operative assessment of smoking, alcohol consumption, nurse-measured body mass index (BMI) and exercise levels were recorded and patients were followed until death or censorship. Survival analysis was carried out and proportional hazards assumptions were assessed graphically using plots and were then formally tested using the PHTEST procedure in STATA. Results: Of the initial 527 patients, 181 (34%) satisfied the inclusion criteria. The total duration of follow up was 480 person-years. At the pre-operative assessment, 75% were overweight or obese, 10.6% were current smokers, 13.1% recorded excess alcohol consumption and 8.5% had physical difficulty climbing stairs. Age, BMI, histopathological stage and physical capacity all independently affected survival (P<0.05). Overweight patients (HR 2.81) and those who had difficulty climbing stairs (HR 3.31) had a significantly poorer survival. Conclusion: The study found evidence that pre-operative exercise capacity and BMI are important independent prognostic factors of survival in patients undergoing curative surgery for CRC

Age-related differences in exercise and quality of life among breast cancer survivors

Purpose: Physical activity has become a focus of cancer recovery research as it has the potential to reduce treatment-related burden and optimize health-related quality of life (HRQoL). However, the potential for physical activity to influence recovery may be age-dependent. This paper describes physical activity levels and HRQoL among younger and older women after surgery for breast cancer and explores the correlates of physical inactivity. Methods: A population-based sample of breast cancer patients diagnosed in South-East Queensland, Australia, (n=287) were assessed once every three months, from 6 to 18 months post-surgery. The Functional Assessment of Cancer Therapy-Breast questionnaire (FACTB+4) and items from the Behavioral Risk Factor Surveillance System (BRFSS) questionnaire were used to measure HRQoL and physical activity, respectively. Physical activity was assigned metabolic equivalent task (MET) values, and categorized as 3, p<0.05). Conclusions: Age influences the potential to observe HRQoL benefits related to physical activity participation. These results also provide relevant information for the design of exercise interventions for breast cancer survivors and highlights that some groups of women are at greater risk of long-term sedentary behavior

Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials

Metastatic Colorectal Cancer; OutcomesCáncer colorrectal metastásico; ResultadosCàncer colorrectal metastàtic; ResultatsBackground We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials. Methods Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first- and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum. All statistical tests were 2-sided. Results Older adults comprised 16.4% of patients on first-line trials (870 total older adults aged >70 years; 4419 total younger adults aged ≤70 years, on first-line trials). Older adults and those with Eastern Cooperative Oncology Group Performance Status >0 were less likely to receive second-line therapy than younger adults. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariable analysis (odds ratio = 1.11, 95% confidence interval = 1.02 to 1.21, P = .01). Older and younger adults enrolled in second-line trials experienced similar median TTP and median OS (median TTP = 5.1 vs 5.2 months, respectively; median OS = 11.6 vs 12.4 months, respectively). Conclusions Older adults were less likely to receive second-line therapy for metastatic colorectal cancer, though we did not observe a statistical difference in survival outcomes vs younger adults following second-line therapy. Further study should examine factors affecting decisions to treat older adults with second-line therapy. Inclusion of geriatric assessment may provide better criteria regarding the risks and benefits of second-line therapy.The National Cancer Institute Gastrointestinal Cancer Center Specialized Programs of Research Excellence (SPORE) Career Development Award (5P50CA127003-08) funded Dr McCleary’s effort. The ARCAD Foundation funded data collection and analysis

Duration of adjuvant chemotherapy for stage III colon cancer

BACKGROUND Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.

Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plamsa membrane

Hemochromatosis type 2 gene (HFE2) is highly expressed in skeletal muscle and liver hepatocytes. Its encoded protein, hemojuvelin (HJV), is a co-receptor for the bone morphogenetic proteins 2 and 4 (BMP2 and BMP4) and enhances the BMP-induced hepcidin expression. Hepcidin is a central iron regulatory hormone predominantly secreted from hepatocytes. HJV also binds neogenin, a membrane protein widely expressed in many tissues. Neogenin is required for the processing and release of HJV from cells. The role that neogenin plays in HJV trafficking was investigated, using HepG2 cells, a human hepatoma cell line. Knockdown of endogenous neogenin markedly suppresses HJV release, but has no evident effect on HJV trafficking to the plasma membrane. Addition of a soluble neogenin ectodomain to cells markedly inhibits HJV release, indicating that the HJV shedding is not processed before trafficking to the cell surface. At the plasma membrane it undergoes endocytosis in a dynamin-independent but cholesterol-dependent manner. The additional findings that HJV release is coupled to lysosomal degradation of neogenin, that HJV undergoes endocytosis, and that cholesterol depletion by filipin blocks both HJV endocytosis and HJV release, suggest that neogenin-mediated HJV release occurs after the HJV-neogenin complex is internalized from the cell surface

Dietary Patterns and Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue

Importance—Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of host immune response to tumor. Evidence also suggests that diet influences intestinal F. nucleatum. However, the role of F. nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown. Objective—To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F. nucleatum in tumor tissue. Design—Prospective cohort study. Setting—The Nurses’ Health Study (1980–2012) and the Health Professionals Follow-up Study (1986–2012). Participants—121,700 US female nurses and 51,529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively, at enrollment. Exposures—Prudent and Western dietary patterns. Main Outcomes and Measures—Incidence of colorectal carcinoma subclassified by F. nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction. Results—We documented 1,019 incident colon and rectal cancer cases with available F. nucleatum data among predominantly white 137,217 individuals over 26–32 years of follow-up encompassing 3,643,562 person-years. The association of prudent diet with colorectal cancer significantly differed by tissue F. nucleatum status (Pheterogeneity = .01). Prudent diet score was associated with a lower risk of F. nucleatum-positive cancers [Ptrend = .003; multivariable hazard ratio of 0.43 (95% confidence interval 0.25–0.72) for the highest vs. the lowest prudent score quartile], but not with F. nucleatum-negative cancers (Ptrend = .47). Dietary component analyses suggested possible differential associations for the cancer subgroups according to intakes of dietary fiber (Pheterogeneity = .02). There was no significant heterogeneity between the subgroups according to Western dietary pattern scores (Pheterogeneity = .23). Conclusions and Relevance—Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F. nucleatum-positive colorectal cancer but not F. nucleatum-negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms