Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries.

In cerebral arteries, alterations of vascular reactivity have been observed but not well molecularly characterized. Therefore, we have hypothesized that cerebrovascular reactivity could be modified by aging via a modification of Ca(2+) signaling in smooth muscle cells. Ca(2+) signals and gene expression implicated in contraction have been measured in posterior and middle cerebral arteries from young (2-3 months) and old (20-22 months) C57Bl6/J mice. Aging induced a decrease of KCl- and caffeine-induced contraction as well as a decrease of the amplitudes and an increase of the durations of KCl- and caffeine-induced Ca(2+) signals. These results could be linked with the decrease of gene expression coding for Cav1.2, RyR2, SERCA2, PLB, STIM1, TRIC-B, and the increase of FKBP12.6 and TPCN1 gene expression. Finally, aging induced a modification of InsP3 subtype expression pattern responsible for a modification of the InsP3 affinity to activate Ca(2+) signals. These results show that aging induces a decrease of contractility correlated with modifications of the expression of genes encoding Ca(2+) signaling toolkit. Globally, the amplitude of Ca(2+) signals was decreased, whereas their duration was increased by a defection of Ca(2+) store refilling.

Factors Associated with End-of-Life Health Service Use in Patients Dying of Cancer.

This study describes acute care hospital death, physician house calls and home care near the end of life among patients who died of cancer and the factors that are associated with these events and services. It is a population-based retrospective study that uses linked administrative healthcare data. The cohort includes all patients who died of cancer between 2000 and 2004 in Ontario, Canada.Fifty-five per cent of patients died in acute care hospital, 68% received home care in the last 6 months of life and 24% received at least one physician house call in the last 2 weeks of life. Increased age was associated with a decreased likelihood of each event or service. Women were less likely to die in acute care and more likely to receive home care. Residents in low-income neighbourhoods were less likely to receive house calls or home care. Patients who received home care or house calls were less likely to die in acute care.Our observations add to those in the literature, suggesting a need to increase the use of supportive care services at the end of life in hopes of decreasing the need for acute care. They also serve as a baseline for future comparison, which is of particular interest since new government policies directed at end-of-life care were recently introduced.

Tolerance and acceptance results of a palladium-103 permanent breast seed implant Phase I/II study.

PURPOSE: To test, in a prospective Phase I/II trial, a partial breast irradiation technique using a 103Pd permanent breast seed implant (PBSI) realized in a single 1-h procedure under sedation and local freezing. METHODS AND MATERIALS: Eligible patients had infiltrating ductal carcinoma < or = 3 cm in diameter, surgical margin > or = 2 mm, no extensive intraductal component, no lymphovascular invasion, and negative lymph nodes. Patients received a permanent seed implant, and a minimal peripheral dose of 90 Gy was prescribed to the clinical target volume, with a margin of 1.5 cm. RESULTS: From May 2004 to April 2007, 67 patients received the PBSI treatment. The procedure was well tolerated, with 17% of patients having significant pain after the procedure. Only 1 patient (1.5%) had an acute skin reaction (Grade 3 according to the National Cancer Institute Common Toxicity Criteria). The rates of acute moist desquamation, erythema, and indurations were 10.4%, 42%, and 27%, respectively. At 1 year the rate of Grade 1 telangiectasia was 14%. The rate of skin reaction decreased from 65% to 28% when skin received less than the 85% isodose. According to a Radiation Therapy Oncology Group questionnaire, 80-90% of patients were very satisfied with their treatment, and the remainder were satisfied. One patient (1.5%) developed an abscess, which resolved after the use of antibiotics. There was no recurrence after a median follow-up of 32 months (range, 11-49 months). CONCLUSIONS: The feasibility, safety, and tolerability of PBSI compares favorably with that of external beam and other partial breast irradiation techniques.

Significance of multifocality in ductal carcinoma in situ: outcomes of women treated with breast-conserving therapy.

PURPOSE: There is concern that women with multifocal ductal carcinoma in situ (DCIS; confined to one quadrant) who are treated with breast-conserving surgery face a high risk of local recurrence; therefore, many are treated with mastectomy. The objective of this study is to evaluate the significance of multifocality and the outcomes of women with multifocal DCIS treated with breast-conserving therapy. METHODS: The records of patients treated with breast-conserving surgery for DCIS between 1982 and 2000 were reviewed. Multivariate analyses were performed to evaluate the effects of multifocality and other prognostic factors on the rate of local recurrence. RESULTS: Of 615 cases of DCIS reviewed, 310 (41%) received breast-conserving surgery and 305 (40%) received breast-conserving surgery plus radiation (n = 260 with multifocality, n = 314 without multifocality, and n = 31 focality unreported). On multivariate analysis, multifocality (hazard ratio [HR] = 1.80; 95% CI, 1.15 to 2.80; P = .01), radiation treatment (HR = 0.46; 95% CI, 0.29 to 0.74; P = .001), margin width 4 mm or smaller (HR = 1.74; 95% CI, 1.03 to 2.92; P = .04), and high nuclear grade (HR = 1.65; 95% CI, 1.02 to 2.65; P = .04) were associated with risk of local recurrence. The detrimental effect of multifocality was limited to women who did not receive radiotherapy; the local recurrence-free survival rate at 10 years was 59% for women with multifocal disease and 80% for women without multifocality (P = .02). Among women treated with breast-conserving surgery plus radiation, there was no difference in 10-year local recurrence-free survival (80% v 87%; P = .35). There was no association between multifocality and the development of invasive recurrence. CONCLUSION: Multifocality is a significant predictor of local recurrence in women who receive breast-conserving surgery for DCIS without radiotherapy; however, low recurrence rates can be achieved if adjuvant radiation is administered.

The management of ductal carcinoma in situ of the breast: a screened population-based analysis.

BACKGROUND: A recent SEER study identified significant variations in the care of women with DCIS, yet several potential confounding variables were not included. We report a patterns of care study of women with DCIS to better understand the gap between evidence-based knowledge and the management of DCIS. METHODS: We studied all cases of DCIS diagnosed through the Ontario Breast Screening Program from 1991 to 2000. Data was obtained by database linkage and chart abstraction. A logistic regression model using generalized estimating equations to adjust for clustering was used. RESULTS: About 320,236 women were screened and 727 individuals were diagnosed with DCIS. The rate of mastectomy was 30% and was associated with multifocality (OR: 3.5 [1.7, 7.1], P = 0.0005), tumor size (OR: >2 cm vs. 1 cm (OR: 2.4 [1.3, 4.4], P = 0.006). Half of cases with margins <1 cm did not receive XRT. CONCLUSIONS: Our study corroborates previous reports on the persistent rates of mastectomy and axillary nodal dissection and the limited use of XRT in the treatment of DCIS.

Indicators of poor quality end-of-life cancer care in Ontario.

This study measures the proportion of cancer patients in Ontario, Canada, with intensive care unit (ICU) admissions, emergency room (ER) visits, or chemotherapy in the last two weeks of life. We used the Ontario Cancer Registry to identify a cohort of cancer patients who died in 2001. These cases were then linked to administrative sources of data to measure each indicator, and to describe the associated clinical and health service factors. In the cohort, 27% had at least one ER visit and 5% had an ICU visit in the last two weeks of life. Of those who received chemotherapy in the last six months, 16% received chemotherapy in the last two weeks of life. Receiving a home care visit in the last six months of life, or a physician house call or a palliative care assessment in the last two weeks of life was consistently associated with decreased odds of each of the indicators. Our results indicate that a significant proportion of Ontario cancer patients have indicators of poor quality end-of-life care. Certain health care factors may influence these indicators.

Complementary and alternative medicine use is associated with an increased perception of breast cancer risk and death.

PURPOSE: Complementary and alternative medicines (CAMS) are frequently used by patients with breast cancer and their use may be related to the presence of psychosocial distress. The objective of this study is to assess the presence of anxiety and depression in breast cancer patients who use CAM and assess how they perceive their risks of recurrence and dying from breast cancer compared to non-users. METHODS: Breast cancer patients attending ambulatory clinics at a single cancer center were approached by their oncologist. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM, views of their risks of developing recurrent cancer, and of dying of breast cancer. The presence of anxiety and depression was scored using the Hospital Anxiety and Depression Scale (HADS). Responses were scored and compared between CAM users and non-users. RESULTS: A total of 251 patients completed the survey. CAM usage was reported by 43% of patients. Individuals who used CAM were younger [53.1 versus 63.0 year (p < 0.001)], had higher education (p < 0.001), were more likely to have full time employment [25.7 versus 16.3% (p < 0.001)] and have private insurance for medications (76 versus 60%, p = 0.007) compared to non-users. CAM users perceived their risk of recurrence (p = 0.011) and death from breast cancer (p = 0.0001) as being significantly greater than non-users. There were no significant differences in anxiety or depression scores between CAM and non-users. CONCLUSION: CAM use is associated with an increased perception of breast cancer recurrence and of breast cancer-related death. There was no association between the presence of anxiety or depression and CAM use. Improved patient understanding of actual risks of recurrence and death are required such that women will be able to make more informed decisions about using CAMs.

Is expert breast pathology assessment necessary for the management of ductal carcinoma in situ ?

BACKGROUND: Current guidelines include a recommendation that a pathologist with expertise in breast disease review all ductal carcinoma in situ (DCIS) specimens due to the presence of significant variability in pathologic reporting of DCIS. The objective of this study was to evaluate the completeness and accuracy of pathologic reporting of DCIS over the past decade and to determine the current impact of expert breast pathology assessment on the management of DCIS. METHODS: All patients with a diagnosis of DCIS referred to a single regional cancer centre between 1982 and 2000 have been reviewed. Inter-observer variability between initial and secondary reports has been evaluated using kappa statistics. For each case, the Van Nuys Prognostic Index (VNPI) using pathologic data obtained from the initial and reviewed pathology reports were compared. The impact of expert breast pathology on risk assessment and treatment was determined. RESULTS: 481 individuals with DCIS were referred and pathology review was performed on 350 patients (73%). Inter-observer agreement was high for the main pathologic features of DCIS. From 1996 to 2000, secondary pathology assessments lead to a change in the assessment of local recurrence risk in 100 cases (29%) and contributed to a change in treatment recommendation in 93 (43%) cases. CONCLUSION: Expert breast pathology assessments continue to be necessary in the management of DCIS.