Challenges in the Management of Breast Cancer in a Low Resource Setting in South East Asia.

BACKGROUND: Breast cancer is the second most common cancer in women in Cambodia, a low income country in SouthEast Asia. The Sihanouk Hospital Centre of Hope (SHCH) is a charity hospital set up by an international nongovernmental organisation, HOPE Worldwide. In 2008, SHCH partnered with AmeriCares, a global health organisation to set up and deliver a breast cancer programme to provide education, diagnosis and treatment for women with breast cancer. The objective of this study is to characterise the presentation, diagnosis, treatment and outcomes of women treated under this program. MATERIALS AND METHODS: A total of 215 women newly diagnosed with breast cancer from 1 March 2008 until 31 March 2011 were studied. Age at diagnosis, tumour size, histological type, tumour grade, ER, lymph node involvement, treatment modalities (surgery, radiotherapy, chemotherapy, hormone therapy) were recorded. Data on mortality at 3 years were obtained whenever possible. RESULTS: The median age was 47 years old. Some 77.8% were diagnosed with stage 3 and 4 lesions, and 78.5% underwent mastectomy, of which 28.4% the intent was palliative. Of those whose ER status were known, only 48.3% were ER positive. Only 6 patients could afford chemotherapy while only 1 patient had radiotherapy. Hormone therapy was provided free for those who were ER positive. The overall survival rate at 3 years was 39.1%. CONCLUSIONS: Breast cancer presents at a late stage, and because treatment is suboptimal, survival is poor in Cambodia. A more aggressive approach to early detection and treatment needs to be developed to improve outcome from this potentially curable disease.

Perceptions among adolescent girls and their mothers regarding tampon use.

STUDY OBJECTIVE: To explore the perceptions of perimenarchal females and their mothers regarding tampons and tampon use. DESIGN: Descriptive study; convenience sample survey. SETTING: Diverse pediatric practice setting. PARTICIPANTS: 139 females 11-18 years of age and 129 of their mothers/female guardians. INTERVENTION: Survey. MAIN OUTCOME MEASURES: Frequencies, chi-square tests, t-tests. RESULTS: Most adolescents (38%-55%) respond "don't know" to various attitude and knowledge items pertaining to tampon use. Adolescent-mother pairs report similar perceptions about tampon use for adolescents. Mothers and adolescents who have "ever tried" tampons (including 68% and 56% of respondents, respectively) have more favorable attitudes about tampons than those who have not tried tampons. Adolescent females list their mothers as the primary source of tampon information; 70% of adolescents and 66% of mothers report that no doctor has spoken to them about tampon use for the daughter. CONCLUSIONS: There is a vast educational deficit among both adolescent females and their mothers regarding the use of tampons among youth. Adolescents and their mothers note that few providers have educated 11- to 18-year-old females or their parents about tampons. Providers have the opportunity to influence adolescent health choices and quality of life associated with tampon use.

Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab.

BACKGROUND: We evaluated shedding of epidermal growth factor type II receptor (Her2/neu) extracellular domain (ECD) in primary uterine serous carcinoma (USC) cell lines and in the serum of USC patients and its biological effects in experiments of trastuzumab-induced cytotoxicity in vitro. METHODS: Her2/neu expression was evaluated by immunohistochemistry (IHC), real-time PCR and flow cytometry, while c-erbB2 gene amplification was assessed using fluorescent in situ hybridisation (FISH). Her2/neu ECD levels in the supernatants of USC cell lines and in the serum of 38 USC patients and 19 controls were tested using ELISA. The biologic effect of Her2/neu ECD on trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated in 5-h chromium-release assays. RESULTS: Five out of ten USC cell lines overexpressed Her2/neu by IHC and showed amplification of the c-erbB2 gene. High levels of Her2/neu ECD were found in supernatants of all FISH-positive tumours. In contrast, FISH-negative USC was negative for Her2/neu ECD shedding. Serum Her2/neu ECD levels in patients harbouring 3+Her2/neu tumours were higher than those found in healthy women (P=0.02) or USC patients with 2+ or 1+/negative Her2/neu expression (P=0.02). In cytotoxicity experiments, trastuzumab-mediated ADCC was significantly decreased by the addition of Her2/neu ECD-containing supernatants (P=0.01). CONCLUSION: FISH-positive c-erbB2 USC cell lines shed high levels of Her2/neu ECD. High levels of Her2/neu ECD in USC patients may reduce trastuzumab-mediated ADCC in vitro and potentially neutralise its therapeutic effect in vivo.

Analysis of vestibular schwannoma size in multiple dimensions: a comparative cohort study of different measurement techniques.

OBJECTIVES: In this volumetric study of the vestibular schwannoma, we evaluated the accuracy and reliability of several approximation methods that are in use, and determined the minimum volume difference that needs to be measured for it to be attributable to an actual difference rather than a retest error. We also found empirical proportionality coefficients for the different methods. DESIGN/SETTING AND PARTICIPANTS: Methodological study with investigation of three different VS measurement methods compared to a reference method that was based on serial slice volume estimates. These volume estimates were based on: (i) one single diameter, (ii) three orthogonal diameters or (iii) the maximal slice area. Altogether 252 T1-weighted MRI images with gadolinium contrast, from 139 VS patients, were examined. MAIN OUTCOME MEASURES: The retest errors, in terms of relative percentages, were determined by undertaking repeated measurements on 63 scans for each method. Intraclass correlation coefficients were used to assess the agreement between each of the approximation methods and the reference method. The tendency for approximation methods to systematically overestimate/underestimate different-sized tumours was also assessed, with the help of Bland-Altman plots. RESULTS: The most commonly used approximation method, the maximum diameter, was the least reliable measurement method and has inherent weaknesses that need to be considered. This includes greater retest errors than area-based measurements (25% and 15%, respectively), and that it was the only approximation method that could not easily be converted into volumetric units. Area-based measurements can furthermore be more reliable for smaller volume differences than diameter-based measurements. CONCLUSIONS: All our findings suggest that the maximum diameter should not be used as an approximation method. We propose the use of measurement modalities that take into account growth in multiple dimensions instead.

Experience with epidural anaesthesia in pregnant women with von Willebrand disease.

The use of epidural anaesthesia (EA) in women with von Willebrand disease (vWD) is limited secondary to fears of complications. Currently, there are no standard recommendations for the use of EA in women with vWD. A retrospective chart review was performed of women with vWD who received EA at the time of term pregnancy. EA was administered to 15 women at the time of 17 deliveries, four by caesarian section and 13 by normal spontaneous vaginal delivery. Ninety-three per cent of these women had type 1 vWD. None of the women received DDAVP or clotting factor concentrates prior to the administration of EA. There were no complications directly related to EA. Postpartum haemorrhage did occur in 47% of the deliveries, with three women requiring blood transfusion. In this small series, EA appears to be safely administered to pregnant type 1 vWD patients at the time of term delivery.

Increased Tie2 expression, enhanced response to angiopoietin-1, and dysregulated angiopoietin-2 expression in hemangioma-derived endothelial cells.

Infantile hemangiomas are endothelial tumors that grow rapidly in the first year of life and regress slowly during early childhood. Although hemangiomas are well-known vascular lesions, little is known about the mechanisms that cause the excessive endothelial cell proliferation in these most common tumors of infancy. To investigate the molecular basis of hemangioma, we isolated endothelial cells from several proliferative-phase lesions and showed that these cells are clonal and exhibit abnormal properties in vitro (E. Boye, Y. Yu, G. Paranya, J. B. Mulliken, B. R. Olsen, J. Bischoff: Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 2001, 107:745-752). Here, we analyzed mRNA expression patterns of genes required for angiogenesis, including members of the vascular endothelial growth factor (VEGF)/VEGF receptor family and the angiopoietin/Tie family, in hemangioma-derived and normal endothelial cells. KDR, Flt-1, Tie1, Tie2, and angiopoietin-2 (Ang2) were strongly expressed in cultured hemangioma-derived endothelial cells and in hemangioma tissue. In contrast, there was little expression of angiopoietin-1 (Ang1) or VEGF. We found Tie2 mRNA and protein up-regulated with a concomitant increase in cellular responsiveness to Ang1 in most hemangioma-derived endothelial cells. Ang2 mRNA was down-regulated in response to serum in hemangioma-derived endothelial cells, but not in normal endothelial cells, suggesting altered regulation. These findings implicate Tie2 and its ligands Ang1 and Ang2 in the pathogenesis of hemangioma.

Fatal accidents following changes in daylight savings time: the American experience.

Objective: This study examines specific hypotheses that both sleep loss and behavioral changes occurring with the time shifts for Daylight Savings Time (DST) significantly effect the number of fatal traffic accidents in the United States of America.Background: It has been reported that there is a significant increase in the number of automobile accidents in the spring shift to DST due to the loss of 1 h of sleep. But the extra hour gained at night with the shift from DST in the fall has been variably reported to be associated with increases and decreases in the number of automobile accidents which may reflect either behavioral anticipation with an extended late night prior to the change or the benefit of extra sleep after the change.Methods: Data from 21 years of United States' fatal automobile accidents were gathered. The mean number of accidents on the days at the time of the shifts (Saturday, Sunday and Monday) was compared to the average of the corresponding mean number of accidents on the matching day of the weeks preceding and following the shift. This was repeated for each DST shift. The number of accidents for a particular shift was also correlated with the year of the accidents.Results: There was a significant increase in accidents for the Monday immediately following the spring shift to DST (t=1.92, P=0.034). There was also a significant increase in number of accidents on the Sunday of the fall shift from DST (P<0.002). No significant changes were observed for the other days. A significant negative correlation with the year was found between the number of accidents on the Saturdays and Sundays but not Mondays.Conclusions: The sleep deprivation on the Monday following shift to DST in the spring results in a small increase in fatal accidents. The behavioral adaptation anticipating the longer day on Sunday of the shift from DST in the fall leads to an increased number of accidents suggesting an increase in late night (early Sunday morning) driving when traffic related fatalities are high possibly related to alcohol consumption and driving while sleepy. Public health educators should probably consider issuing warnings both about the effects of sleep loss in the spring shift and possible behaviors such as staying out later, particularly when consuming alcohol in the fall shift. Sleep clinicians should be aware that health consequences from forced changes in the circadian patterns resulting from DST come not only from physiological adjustments but also from behavioral responses to forced circadian changes.

Aspirin in heart disease, transient ischemic attacks, and stroke.

The link between acetylsalicylic acid and the reduction of incidence in myocardial infarction has generated a great deal of interest among physicians and the general public. The author reviews recent literature on the use of ASA and describes the complex pharmacologic mechanism that may be responsible for the beneficial effects of ASA in such diverse situations as toothaches and heart attacks.