Extracapsular Extension in Positive Axillary Lymph Nodes in Female Breast Cancer Patients

BACKGROUND AND PURPOSE: There has been little information regarding lymph node-positive breast cancer patients with extracapsular extension (ECE). The aim of this study was to evaluate the role of ECE in predicting survival and relapse rates. PATIENTS AND METHODS: From 1994-2002, 1,078 lymph node-positive women with breast carcinoma were treated at our institution, whereas 301 patients (27.9%) presented with ECE. 91 patients (30.2%) were identified as having three or less lymph nodes involved, 27.9% patients four to six, 15.6% patients seven to nine, and 26.2% patients ten or more nodes, respectively. The median age was 58.4 years (range: 28-84 years) and the median follow-up 34 months (range: 2-99 months). Nodal irradiation was given to patients with four or more positive lymph nodes. Chemotherapy was administered to 69.8%, hormonal therapy to 53.2%, and combined systemic treatment to 26% of patients. RESULTS: The 1-, 3-, and 5-year overall survival (OS) was 98%, 84%, and 73%, the 1-, 3-, and 5-year disease-free survival (DFS) 95%, 69%, and 58%, and the 1-, 3-, and 5-year metastasis-free survival (MFS) 96%, 73%, and 60%. The relapse rates were 6.6% (local), 0.3% (supraclavicular), 0.7% (isolated axillary), 1% (local + axillary), and 0.7% (local + supraclavicular), respectively. 81 patients (27%) developed distant metastases. In December 2002, 245 patients (81.4%) were alive, 202/245 without progression, 32/245 with distant metastases, 5/245 with local/locoregional recurrence, and 6/245 patients with local and distant failure. CONCLUSION: Isolated axillary nodal failure remains low in lymph node-positive patients with ECE. Balancing the risks and benefits of irradiation, we continue to recommend that complete axillary irradiation is not routinely indicated after adequate axillary dissection.     

Issues of Establishment, Consolidation, and Reorganization in Biobehavioral Adaptation

Two strains of male mice have bred over fortygenerations, starting with the work of RobertCairns and his colleagues, one strain with ahigh level of intra-species aggression, theother a low level of aggression. Thehigh-aggression mice tend to establishdominance hierarchies and particularly fight inthe presence of female mice. Thelow-aggression mice tend, in groups of theirown, to have a high degree of low-intensity,peaceful social contact, and to be more timidin initiating action than the high-aggressionmice. Biochemical differences have beenobserved between the two strains, and confirmedby the present data: the high-aggression micehave greater dopamine concentrations (in thecaudate nucleus and nucleus accumbens), lowerlevels of the stress hormone corticosterone,and higher levels of testosterone than thelow-aggression mice. The current experimentswere designed to answer questions about theflexibility of adaptive behaviors:specifically, what is the effect of early dailymaternal separation on adult stress response ineach strain? What are the behavioral andhormonal mechanisms by which, as has beenobserved, low-aggression mice achieve adominant status when brought into situationswhere they compete for territory withhigh-aggression mice? Finally, what are thesocial and neurochemical mechanisms by whichhigh-aggression mice can develop low-aggressionbehavior if brought out of isolation and intogroups?Maternal separation was found to lead todecreases in stress levels, as measured bycorticosterone, in the low-aggression but notthe high-aggression, mice – presumably becauseof the surplus of maternal care the pupsreceive on returning to the nest. When alow-aggression mouse became dominant and ahigh-aggression mouse became submissive, theirusual pattern of corticosterone andtestosterone levels was found to be reversed. The change to low-aggression behavior inhigh-aggression mice switching from anisolation condition to a group condition, wasmediated by a decrease in D₁ dopaminereceptor densities.These results, like the ones on which theybuild, argue for substantial developmentalinfluences in expressions of the genesinfluencing aggressive or cooperative behavior. In this approach to evolution, epigenesis istreated not as a set of traits and behaviorspredetermined by the genome, but as a set ofprobabilistic tendencies toward certain traitsand behaviors.     

African American bereaved family members' perceptions of the quality of hospice care: lessened disparities, but opportunities to improve remain

Previous research has documented striking disparities in bereaved family members' perceptions of the quality of end-of-life care between African American and white decedents. Using data from the 2005 repository of the Family Evaluation of Hospice Care survey, we examined whether this disparity in quality of end-of-life care persists once an African American is enrolled in hospice. Of the 121,817 decedents whose proxies were surveyed, 4,095 were non-Hispanic black (African American), and 97,525 were non-Hispanic white. There were no statistically significant differences with regard to decedents' gender. Length of stay on hospice was similar across racial groups. Although previous research has demonstrated striking disparities in the perceived quality of end-of-life care, we found that there were either no differences (quality ratings scores) or less of a disparity in perceptions of concerns with the quality of end-of-life care when compared to the results of a previously reported national mortality follow-back survey, suggesting that though disparities in perceptions of care at end of life persist, on hospice they improve to some degree.     

Adoption of Expansion Margins to Reduce the Dose Received by the Coronary Arteries and the Risk of Cardiovascular Events in Lymphoma Patients

PurposeMediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit.Methods and MaterialsForty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (D_max), median (D_med), and mean (D_mean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications.ResultsPlan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in D_max, D_med, and D_mean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV.ConclusionsIntegration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.     

Dimethylarginines in patients with intracerebral hemorrhage: association with outcome,hematoma enlargement,and edema

Background

Asymmetric dimethylarginine (ADMA)––the most potent endogenous NO-synthase inhibitor, has been regarded as mediator of endothelial dysfunction and oxidative stress. Considering experimental data, levels of ADMA and its structural isomer symmetric dimethylarginine (SDMA) might be elevated after intracerebral hemorrhage (ICH) and associated with clinical outcome and secondary brain injury.

Methods

Blood samples from 20 patients with acute ICH were taken at?≤?24 h and 3 and 7 days after the event. Nine patients had favorable (modified Rankin Scale (mRS) at 90 days 0–2) outcome, and 11 patients unfavorable outcome (mRS 3–6). Patients’ serum ADMA, SDMA, and L-arginine levels were determined by high-performance liquid chromatography–tandem mass spectrometry. Levels were compared to those of 30 control subjects without ICH. For further analysis, patients were grouped according to outcome, hematoma and perihematomal edema volumes, occurrence of hematoma enlargement, and cytotoxic edema as measured by computed tomography and serial magnetic resonance imaging.

Results

Levels of ADMA––but not SDMA and L-arginine––were elevated in ICH patients compared to controls (binary logistic regression analysis: ADMA?≤?24 h, p?=?0.003; 3 days p?=?0.005; 7 days p?=?0.004). If patients were grouped according to outcome, dimethylarginines were increased in patients with unfavorable outcome. The binary logistic regression analysis confirmed an association of SDMA levels?≤?24 h (p?=?0.048) and at 3 days (p?=?0.028) with unfavorable outcome. ADMA?≤?24 h was increased in patients with hematoma enlargement (p?=?0.003), while SDMA?≤?24 h was increased in patients with large hematoma (p?=?0.029) and perihematomal edema volume (p?=?0.023).

Conclusions

Our data demonstrate an association between dimethylarginines and outcome of ICH. However, further studies are needed to confirm this relationship and elucidate the mechanisms behind.