Climate variability and Aedes vector indices in the southern Philippines: An empirical analysis.

BACKGROUND: Vector surveillance is an essential public health tool to aid in the prediction and prevention of mosquito borne diseases. This study compared spatial and temporal trends of vector surveillance indices for Aedes vectors in the southern Philippines, and assessed potential links between vector indices and climate factors. METHODS: We analysed routinely collected larval and pupal surveillance data from residential areas of 14 cities and 51 municipalities during 2013-2018 (House, Container, Breteau and Pupal Indices), and used linear regression to explore potential relationships between vector indices and climate variables (minimum temperature, maximum temperature and precipitation). RESULTS: We found substantial spatial and temporal variation in monthly Aedes vector indices between cities during the study period, and no seasonal trend apparent. The House (HI), Container (CI) and Breteau (BI) Indices remained at comparable levels across most surveys (mean HI = 15, mean CI = 16, mean BI = 24), while the Pupal Productivity Index (PPI) was relatively lower in most months (usually below 5) except for two main peak periods (mean = 49 overall). A small proportion of locations recorded high values across all entomological indices in multiple surveys. Each of the vector indices were significantly correlated with one or more climate variables when matched to data from the same month or the previous 1 or 2 months, although the effect sizes were small. Significant associations were identified between minimum temperature and HI, CI and BI in the same month (R2 = 0.038, p = 0.007; R2 = 0.029, p = 0.018; and R2 = 0.034, p = 0.011, respectively), maximum temperature and PPI with a 2-month lag (R2 = 0.031, p = 0.032), and precipitation and HI in the same month (R2 = 0.023, p = 0.04). CONCLUSIONS: Our findings indicated that larval and pupal surveillance indices were highly variable, were regularly above the threshold for triggering vector control responses, and that vector indices based on household surveys were weakly yet significantly correlated with city-level climate variables. We suggest that more detailed spatial and temporal analyses of entomological, climate, socio-environmental and Aedes-borne disease incidence data are necessary to ascertain the most effective use of entomological indices in guiding vector control responses, and reduction of human disease risk.

Elevated levels of perfluoroalkyl substances in breast cancer patients within the Greater Manila Area.

Several studies have reported exposure of humans to various endocrine disrupting chemicals (EDCs) worldwide. However, there is a lack of data regarding EDC exposures in humans living in Southeast Asian countries, such as the Philippines. Hence, this study measured levels of 41 EDCs in women residing in the Greater Manila Area, home to the second largest city in Southeast Asia. Urine samples from women with versus without breast cancer were analyzed for 11 phthalate metabolites, 8 environmental phenols, and 10 bisphenols, while serum samples were analyzed for 12 perfluoroalkyl substances (PFAS). Out of the four groups of EDCs analyzed, PFAS were significantly associated with breast cancer (adjusted OR = 13.63, 95% CI: 3.24-94.88 p-trend = 0.001 for PFDoA; adjusted OR = 9.26, 95% CI 2.54-45.10, p-trend = 0.002 for PFDA; and adjusted OR = 2.66, 95% CI: 0.95-7.66, p-trend = 0.004 for PFHxA). Long-chain PFAS levels were positively correlated with age and were significantly higher in women from Region IV-A, a heavily industrialized region, than from the National Capital Region. Overall, this study showed baseline information regarding the level of EDCs in Filipinas, providing a glimpse of EDC exposure in women living in a megalopolis city in Southeast Asia.

A Pilot Cancer-Phenome Biobanking System in a Low-Resource Southeast Asian Setting: The Philippine General Hospital Biobank Experience.

Biobanking has become an indispensable tool for translational research and health innovations. While the field of biobanking has progressed and evolved globally, biobanking in developing Association of Southeast Asian Nations (ASEAN) countries such as the Philippines remains underrepresented because of several challenges often encountered in these low- and middle-income countries. Recently, the Philippine government has undertaken enormous efforts to advancing research and development in the country, and one of the current research pursuits is the establishment of biobanks, with the hope of attaining more discoveries and innovations in the future. Given that cancer remains a leading cause of death in the Philippines, the Philippine government supported the establishment of a cancer biobank at the Philippine General Hospital (PGH). In this study, we present a specific use case of biobanking activity at the PGH Biobank, to build a cohort of biospecimens from Filipino patients with breast, endometrial, and ovarian cancer. This initiative is part of a biomonitoring study (1) to assess environmental exposures and possible risk factors in the Philippine population and (2) to develop a system of culturing human cells from Filipino patients for subsequent in vitro studies. We discuss issues faced and the solutions developed during the implementation of the biobank. Strong research collaboration, a funding source, basic infrastructure, and appropriate technology helped initiate this pilot biobank in the Philippines. Overall, the experiences of establishing the PGH Biobank may help other institutions in low-resource countries to set up cancer biobanks.

Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population.

Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)-negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial.Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic.Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score.Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422-31. ©2017 AACR.

Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer.

PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes. METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase. RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%. CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

BACKGROUND: For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. METHODS: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. RESULTS: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. CONCLUSIONS: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer.

BACKGROUND: In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first 12 months (P < .0001) and then began to stabilize. CONCLUSIONS: Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck.

CYP2D6 genotypes, endoxifen levels, and disease recurrence in 224 Filipino and Vietnamese women receiving adjuvant tamoxifen for operable breast cancer.

BACKGROUND: While tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results. FINDINGS: In an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case-control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease. We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control. CONCLUSIONS: This exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.

A randomized, double-blinded placebo-controlled clinical trial of the routine use of preoperative antibiotic prophylaxis in modified radical mastectomy.

BACKGROUND: The effectiveness of antibiotic prophylaxis for prevention of surgical site infection (SSI) following specific types of breast cancer surgery remains uncertain. This study assessed the effectiveness of prophylaxis in modified radical mastectomy (MRM). METHODS: Women undergoing MRM for breast cancer were recruited. Women were excluded who had diabetes mellitus, severe malnutrition or known allergy to cephalosporins; were receiving corticosteroid therapy or were treated with antibiotics within one week prior to surgery; were scheduled for simultaneous breast reconstruction or bilateral oophorectomy; had existing local infection. Participants were randomized to receive either intravenous cefazolin 1 g or placebo within 30 min prior to skin incision. Standard skin preparation and operative technique for MRM were carried out. Wounds were assessed for SSI and other complications weekly for 30 days. RESULTS: A total of 254 women were recruited. Age, clinical stage, prior chemotherapy, and operative time were similar for antibiotic and placebo groups. The overall incidence of SSI was 14.2 %. There were no significant differences in the infection rate over the 30-day follow-up period between the placebo and antibiotic groups (15 % vs 13.4 %; p = 0.719) or at each week. The majority of SSI were either cellulitis or superficial infection for both groups. There were no significant differences between groups in treatments required for SSI, incidence of hematoma or seroma. CONCLUSIONS: The findings of this study, alone and when meta-analyzed with data from studies in similar surgical populations, do not support the use of antibiotic prophylaxis in MRM.

Cancer incidence and survival in Metro Manila and Rizal province, Philippines.

The database of two population-based cancer registries (Philippine Cancer Society-Manila Cancer Registry and Department of Health-Rizal Cancer Registry) was used to generate age-standardized incidence rates of cancer during 1980-2002. Five-year relative survival rates were obtained for incident cases from 1993 to 2002 using a period analysis method. Overall incidence had increased in both males and females. Among males, lung cancer was the leading cancer and reached a peak in 1988-92. Colorectal and prostate cancers showed rising trends and became more common than liver cancer, with stable incidence over time. Stomach cancer incidence fell steeply. Among females, there was a steady increase in incidence of breast cancer. There was a slight decrease in the incidence of the second common cancer, cervical cancer, and colorectal cancer became equally common. Lung cancer incidence in females also reached a peak by 1998-2002 and then slightly decreased. Oral cavity cancer decreased strongly in the last period. In general, survival rates among Philippine residents were one-third lower than among Filipino-Americans and Whites in the USA especially in cancer sites wherein effective early detection methods may be available such as breast, cervix, colorectal and thyroid cancers. Survival was also lower in Philippine leukemia cases, a disease wherein effective treatment is proven in some types but is quite expensive. Lifestyle factors such as smoking, unhealthy diet, physical inactivity, and human papillomavirus and hepatitis B virus infections were associated with some incidence patterns. Late stage at diagnosis was largely responsible for low survival.

Inter-country and ethnic variation in colorectal cancer survival: comparisons between a Philippine population, Filipino-Americans and Caucasians.

BACKGROUND: Previous population-based studies showed differences in international and within country colorectal cancer survival estimates, but few investigated the role of prognostic factors. Using a "high resolution approach", we aimed to determine the effect of ethnicity and health care by comparing Filipino-Americans with Philippine residents, who have the same ethnicity, and with Caucasians living in the US, who have the same health care system. METHODS: Using databases from the Manila and Rizal Cancer Registries and the United States Surveillance, Epidemiology and End Results, age-adjusted five-year absolute and relative survival estimates were computed and compared between Filipino-American colorectal cancer patients, cancer patients from the Philippines and Caucasian patients. Cox proportional hazards modelling was used to determine factors affecting survival differences. RESULTS: Much lower 5-year relative survival estimates were obtained for Philippine residents (37%) as compared to those in Filipino-Americans (60.3%) and Caucasians (62.4%). Differences in age, stage and receipt of surgery explained a large proportion of the survival differences between Philippine residents and Filipino-Americans. However, strong excess risk of death for Philippine residents remained after controlling for these and other variables (relative risk, RR, 2.03, 95% confidence interval, 95% CI, 1.83-2.25). CONCLUSIONS: Strong survival disadvantages of Philippine residents compared to Filipino-American patients were disclosed, which most likely reflect differences in access to and utilization of health care. Health education and advocacy, for both patients and health practitioners, should likewise be given priority.

Breast cancer hormone receptor assay results of core needle biopsy and modified radical mastectomy specimens from the same patients.

BACKGROUND: Hormone receptor (HR) expression is the most important biomarker and is the cornerstone in the management of breast cancer. Therefore, the accuracy of its testing is critical in treatment decisions. PATIENTS AND METHODS: A total of 160 consecutive patients accrued to an adjuvant hormonal therapy clinical trial between March 2003 and May 2008 were studied. Estrogen receptor (ER) and progesterone receptor (PgR) protein assays of tissues from modified radical mastectomy (MRM) specimens were compared with their previous core needle biopsy (CNB) ER and PgR immunohistochemical assay results. RESULTS: The tumors of 146 (91.2%) out of the 160 patients with CNB HR-positive disease remained HR positive in MRM specimen assays. Estrogen receptor positivity decreased from 95% in the CNB to 81.9% in MRM specimens and PgR positivity from 93.8% to 86.9%. The overall agreement between CNB and MRM specimens was 81.9% for ER and 85.6% for PgR. The mean Allred scores were significantly higher in CNB than in MRM specimens: ER, 6.6 (SD, 2.02) versus 4.71 (SD, 2.62); PgR, 6.68 (SD, 2.16) versus 5.99 (SD, 2.68); P < .001 and P = .001, respectively. CONCLUSION: Core needle biopsy specimens are associated with the identification of more frequent and higher levels of tumoral hormonal receptor proteins than MRM specimens. Delayed fixation of MRM tissues likely accounted for this finding. Optimal selection of patients for hormonal therapies is dependent on tissue management strategies before formal hormonal receptor protein testing procedures.

Breast cancer survival in different country settings: comparisons between a Filipino resident population, Filipino-Americans and Caucasians.

Various international comparisons of breast cancer survival have shown discrepancies which may reflect the impact of ethnicity or health care. Using databases from SEER 13 and from the Manila and Rizal Cancer Registries, age adjusted five-year absolute and relative survival estimates were computed and compared between Filipino-American breast cancer patients, Philippine residents and Caucasians in the US. Determinants of survival differences were examined using Cox proportional hazards modelling. Age adjusted five-year relative survival was almost identical in Filipino-Americans (89.1%) and Caucasians (87.7%), but much lower in the Philippine residents (58.4%). Large tumor size, lymph node involvement, distant metastasis, and the large proportion of women not receiving surgery explained a substantial portion of the excess mortality in Philippine residents. The moderate excess risk of Caucasians compared to Filipino-Americans was explained by age differences. Access to, utilization and affordability of cancer care facilities are important for reducing breast cancer deaths in developing countries.

Ovarian cancer survival population differences: a "high resolution study" comparing Philippine residents, and Filipino-Americans and Caucasians living in the US.

BACKGROUND: In contrast to most other forms of cancer, data from some developing and developed countries show surprisingly similar survival rates for ovarian cancer. We aimed to compare ovarian cancer survival in Philippine residents, Filipino-Americans and Caucasians living in the US, using a high resolution approach, taking potential differences in prognostic factors into account. METHODS: Using databases from the SEER 13 and from the Manila and Rizal Cancer Registries, age-adjusted five-year absolute and relative survival estimates were computed using the period analysis method and compared between Filipino-American ovarian cancer patients with cancer patients from the Philippines and Caucasians in the US. Cox proportional hazards modelling was used to determine factors affecting survival differences. RESULTS: Despite more favorable distribution of age and cancer morphology and similar stage distribution, 5-year absolute and relative survival were lower in Philippine residents (Absolute survival, AS, 44%, Standard Error, SE, 2.9 and Relative survival, RS, 49.7%, SE, 3.7) than in Filipino-Americans (AS, 51.3%, SE, 3.1 and RS, 54.1%, SE, 3.4). After adjustment for these and additional covariates, strong excess risk of death for Philippine residents was found (Relative Risk, RR, 2.45, 95% confidence interval, 95% CI, 1.99-3.01). In contrast, no significant differences were found between Filipino-Americans and Caucasians living in the US. CONCLUSION: Multivariate analyses disclosed strong survival disadvantages of Philippine residents compared to Filipino-American patients, for which differences in access to health care might have played an important role. Survival is no worse among Filipino-Americans than among Caucasians living in the US.

Ethnicity and health care in cervical cancer survival: comparisons between a Filipino resident population, Filipino-Americans, and Caucasians.

Few studies have assessed and compared cervical cancer survival between developed and developing countries, or between ethnic groups within a country. Fewer still have addressed how much of the international or interracial survival differences can be attributed to ethnicity or health care. To determine the role of ethnicity and health care, 5-year survival of patients with cervical cancer was compared between patients in the Philippines and Filipino-Americans, who have the same ethnicity, and between Filipino-Americans and Caucasians, who have the same health care system. Cervical cancer databases from the Manila and Rizal Cancer Registries and Surveillance, Epidemiology, and End Results 13 were used. Age-adjusted 5-year survival estimates were computed and compared between the three patient groups. Using Cox proportional hazards modeling, potential determinants of survival differences were examined. Overall 5-year relative survival was similar in Filipino-Americans (68.8%) and Caucasians (66.6%), but was lower for Philippine residents (42.9%). Although late stage at diagnosis explained a large proportion of the survival differences between Philippine residents and Filipino-Americans, excess mortality prevailed after adjustment for stage, age, and morphology in multivariate analysis [relative risk (RR), 2.07; 95% confidence interval (CI), 1.68-2.55]. Excess mortality decreased, but persisted, when treatments were included in the multivariate models (RR, 1.78; 95% CI, 1.41-2.23). A moderate, marginally significant excess mortality was found among Caucasians compared with Filipino-Americans (adjusted RR, 1.22; 95% CI, 1.01-1.47). The differences in cervical cancer survival between patients in the Philippines and in the United States highlight the importance of enhanced health care and access to diagnostic and treatment facilities in the Philippines.

Epidemiology and clinicopathology of breast cancer in metro Manila and Rizal Province, Philippines.

The breast cancer incidence in the Philippines is among the highest in Asia. Age-standardized incidence rates (ASR) in Metro Manila and Rizal Province derived from the Philippine Cancer Society-Manila Cancer Registry and the Department of Health-Rizal Cancer Registry showed increase from 1980 to 2002, and were significantly higher in 7 cities in Metro Manila and significantly lower in 14 cities/municipalities mostly in Rizal Province. The AJCC Clinical Stage did not change from 1993 to 2002 among incident cases, the average distribution being: I= 5%, IIA= 20%, IIB= 18%, IIIA= 9%, IIIB= 10%, IV= 11%, Unknown= 28%. The International Agency for Research on Cancer attempted to run a randomized screening trial in 1995-1997 in the Philippines based on clinical breast examination by trained nurses and midwives. Unfortunately, even after home visits by a team equipped to perform needle biopsy, only 35% of screen-positive cases eventually had a diagnostic test. The estimated prevalence of BRCA mutations among unselected patients in the Philippine General Hospital (PGH) in 1998 was 5.1%, with a prevalence of 4.1% for BRCA2 mutations alone. There is a continuing effort at improving IHC hormone receptor testing at PGH, particularly on early fixation in buffered formalin. It was observed that hormone receptor-positive proportions tended to be higher in core needle biopsy specimens (72%) compared to mastectomy specimens (65%). During the years 1991, 1994 and 1997, 97% of incident cases of early breast cancer underwent modified radical mastectomy, 18% had postoperative radiotherapy, 51% had adjuvant hormone treatment and 47% received adjuvant chemotherapy. Survival of incident cases in 1993 to 2002 was compared to that of Filipino-Americans and Caucasians in the SEER 13 database. The age-adjusted 5-year relative survival, using period analysis, of Metro Manila residents, Filipino-Americans and Caucasians were 58.6%, 89.6% and 88.3% respectively.

Surgical oophorectomy for breast cancer: back to the future.

While the preponderance of current scientific presentations on breast cancer therapies has focused on chemotherapeutic strategies, targeted therapy with tyrosine kinase inhibitors and hormonal therapies for postmenopausal women, the majority of worldwide cases of breast cancer occur in premenopausal women, for whom practical inexpensive hormonal therapy, surgical oophorectomy, is the most common attainable treatment. In hormone-receptor-positive breast cancer, meta-analysis data from older trials, and more specific recent trial data have made clearer the chronic natural history of this broad subtype of disease and the central role of hormonal therapy in its control. Greater understanding of the critical variables in pathology procedures for breast tumor tissue hormonal receptor testing is leading to better definitions of the specific patients for whom hormonal therapies are indicated. Closer examination of outcomes following surgical oophorectomy has suggested that more than just downregulation of estrogen stimulated breast cancer growth; the reduction of systemic estrogen levels also occurs with this procedure. When combined with antiestrogen treatment using tamoxifen in patients who are active metabolizers of this drug, surgical oophorectomy is a remarkably effective and cost-effective treatment. This combination of circumstances suggests that this first hormonal therapy for breast cancer may once again, have a much greater role globally.

Clinical and molecular biologic characteristics of early-onset versus late-onset colorectal carcinoma in Filipinos.

A case-control study of Filipino patients who underwent surgical resection for colorectal cancer (CRC) during a 1-year period was undertaken. Thirty-five patients under age 40 years were identified. Paraffin blocks of these and 35 randomly selected patients over age 40 underwent histologic and immunohistochemical evaluation. Markers chosen for evaluation included the apoptosis-associated gene products (p53 and bcl-2), a tumor proliferation activity-related factor (Ki-67), and the markers (MLH1 and MSH2) of DNA microsatellite instability (MSI). Results were correlated with age and the stage and location of the tumor. The average age of the early-onset group was 30.7 years compared to the late-onset group at 67.0 years; and the male/female ratio was equivalent. The younger patients had a significantly higher Dukes' stage, the tumors were more poorly differentiated, and they were more frequently of the mucinous and signet ring cell histopathologic type. Expression of p53 was higher in the younger patients ( p < 0.001) and was independent of the degree of differentiation or the stage of the tumor. No differences of expression were noted for the other markers measured. The increased frequency of CRC in Filipino patients less than 40 years of age offers a unique opportunity to gain a better understanding of carcinogenesis, which might be exploited during diagnosis and management. The differences noted between the early- and late-onset CRC are provocative and provide an impetus for increased screening in Filipinos.

Comparative analysis of hemostatic agents in a swine model of lethal groin injury.

BACKGROUND: Techniques for better hemorrhage control after injury could change outcome. A large-animal model of lethal, uncontrolled hemorrhage was developed to test whether the use of various hemostatic agents would decrease bleeding and improve early survival. METHODS: A complex groin injury was created in 30 Yorkshire swine (42-55 kg) to produce uncontrolled hemorrhage. This injury included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 5 minutes, the animals were randomized to (n = 6 animals per group) no dressing (ND), standard dressing (SD), SD and Rapid Deployment Hemostat (RDH) bandage, SD and QuikClot hemostatic agent (QC), or SD and TraumaDEX (TDEX). Limited volume 0.9% saline (1,000 mL over 30 minutes) resuscitation was started 30 minutes after injury. We measured blood loss, early mortality (180 minutes), and physiologic markers of hemorrhagic shock (e.g., cardiac output, blood pressure, hemoglobin, metabolic acidosis). RESULTS: Application of wound dressing decreased mortality in all groups compared with the ND group (83% mortality). However, this difference was significant (p < 0.05) only for the QuikClot hemostatic agent (0% mortality). Before the application of dressing (first 5 minutes), there were no differences in blood loss between the groups. After application of dressings, the QC group had the lowest blood loss (4.4 +/- 1.4 mL/kg). CONCLUSION: Of the hemostatic agents tested, QuikClot improved survival and decreased bleeding in a swine model of lethal vascular and soft tissue injury.