Factors influencing patient decision-making between simple mastectomy and surgical alternatives.

Background: Despite similar survival rates, breast-conserving therapy (BCT) remains a distant second choice after simple mastectomy for patients with early-stage breast cancer in Singapore. Uptake of reconstruction after mastectomy is also low (18 per cent). The aim of this study was to explore the factors influencing a patient's choice for mastectomy when eligible for BCT, and why patients decline reconstruction after mastectomy. Methods: Patients from the National Cancer Centre Singapore, who were eligible for BCT but chose mastectomy without reconstruction, between December 2014 and December 2015 were included. An interviewer-administered questionnaire focusing on patients' reasons for choosing mastectomy over BCT and not opting for immediate breast reconstruction after mastectomy was used. Tumour characteristics were retrieved from medical records. Spearman's rank correlation coefficient, Mann-Whitney U and Kruskal-Wallis tests were used to analyse the correlation between the patient's self-rated influential factors and variables. Statistical significance was taken as P < 0·050. Results: Ninety-one patients were included (90·1 per cent response rate). The main reasons for choosing mastectomy over BCT were: fear of cancer recurrence (considered very important in 74 per cent), the perception that health outweighs breast retention (49 per cent) and the possibility of second surgery for margins (40 per cent). Key factors for rejecting immediate reconstruction after mastectomy were: patient-perceived 'old age' (very important in 53 per cent), concern about two sites of surgery (42 per cent) and financial cost (29 per cent). Given a second chance, 19·8 per cent of patients would undergo BCT instead of mastectomy. Conclusion: This study has identified the considerations that women in Singapore have when deciding on breast cancer surgery. Some perceptions need to be addressed for women to make a fully informed decision, especially as one-fifth regret their initial choice.

Arginase II inhibition prevents nitrate tolerance.

BACKGROUND AND PURPOSE: Nitrate tolerance, the loss of vascular responsiveness with continued use of nitrates, remains incompletely understood and is a limitation of these therapeutic agents. Vascular superoxide, generated by uncoupled endothelial NOS (eNOS), may play a role. As arginase competes with eNOS for L-arginine and may exacerbate the production of reactive oxygen species (ROS), we hypothesized that arginase inhibition might reduce nitrate tolerance. EXPERIMENTAL APPROACH: Vasodilator responses were measured in aorta from C57Bl/6 and arginase II knockout (argII -/-) mice using myography. Uncoupling of eNOS, determined as eNOS monomer : dimer ratio, was assessed using low-temperature SDS-PAGE and ROS levels were measured using L-012 and lucigenin-enhanced chemiluminescence. KEY RESULTS: Repeated application of glyceryl trinitrate (GTN) on aorta isolated from C57Bl/6 mice produced a 32-fold rightward shift of the concentration-response curve. However this rightward shift (or resultant tolerance) was not observed in the presence of the arginase inhibitor (s)-(2-boronethyl)-L-cysteine HCl (BEC; 100 µM) nor in aorta isolated from argII -/- mice. Similar findings were obtained after inducing nitrate tolerance in vivo. Repeated administration of GTN in human umbilical vein endothelial cells induced uncoupling of eNOS from its dimeric state and increased ROS levels, which were reduced with arginase inhibition and exogenous L-arginine. Aortae from GTN tolerant C57Bl/6 mice exhibited increased arginase activity and ROS production, whereas vessels from argII -/- mice did not. CONCLUSION AND IMPLICATIONS: Arginase II removal prevents nitrate tolerance. This may be due to decreased uncoupling of eNOS and consequent ROS production.

Hormone replacement therapy in women with spinal cord injury - a survey with literature review.

STUDY DESIGN: Postal questionnaire survey. OBJECTIVE: To examine the current use of hormone replacement therapy (HRT) in a sample of menopausal women with spinal cord injury (SCI). SETTING: National Spinal Injuries Centre (NSIC), Stoke Mandeville Hospital, Aylesbury, UK. METHOD: A postal questionnaire was sent to 94 women from the NSIC patient database who met the study inclusion criteria (wheelchair dependent, aged 49 years and above, last seen or heard from within the last 3 years). RESULTS: A total of 59 valid questionnaires were analysed. At the time of the survey, 50 women were menopausal and 11 of them were using HRT, six for menopausal symptoms and five for osteoporosis prevention. Another 11 had used HRT, eight for menopausal symptoms and three for osteoporosis prevention, but had discontinued it. The main reasons for stopping HRT were side effects. Of the 28 women who had never been on HRT, 20 had either enquired about it, or had been offered HRT, but decided against it. Of the nine women who were still premenopausal at the time of the survey, four would consider using HRT. CONCLUSIONS: Results show that 44% of the menopausal women in our sample have used HRT at some point and 22% still do, mostly for treatment of menopausal symptoms and for osteoporosis prevention. In view of the latest literature findings in able-bodied women, use of HRT for osteoporosis prevention in women with SCI may have to be reconsidered.