Logit Kernel is a discrete choice model that has an i.i.d. extreme value (or Gumbel) additive dis... more Logit Kernel is a discrete choice model that has an i.i.d. extreme value (or Gumbel) additive disturbance à la multinomial logit as well as a flexible disturbance, which could be normal, additive, or otherwise. The result is an intuitive, practical, and powerful model that combines the flexibility of probit (and more) with the tractability of logit. For this reason, logit
Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding ... more Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs...
Proceedings of the National Academy of Sciences of the United States of America, Jan 8, 2015
To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical sa... more To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical samples spanning normalcy, increasingly severe cervical intraepithelial neoplasia (CIN1- CIN3), and cervical cancer (CxCa) from multiple perspectives, revealing a cascade of progressive changes. Compared with normal tissue, expression of many DNA replication/repair and cell proliferation genes was increased in CIN1/CIN2 lesions and further sustained in CIN3, consistent with high-risk human papillomavirus (HPV)-induced tumor suppressor inactivation. The CIN3-to-CxCa transition showed metabolic shifts, including decreased expression of mitochondrial electron transport complex components and ribosomal protein genes. Significantly, despite clinical, epidemiological, and animal model results linking estrogen and estrogen receptor alpha (ERα) to CxCa, ERα expression declined >15-fold from normalcy to cancer, showing the strongest inverse correlation of any gene with the increasing expression ...
Macbridea alba is a herbaceous perennial mint endemic to the panhandle region of Florida. We used... more Macbridea alba is a herbaceous perennial mint endemic to the panhandle region of Florida. We used starch gel electrophoresis to describe allozyme diversity and genetic structure in this federally threatened plant. Ten populations were analyzed, with an average sample size of 47 plants (range 41-48 plants) per population. Of the 22 loci analyzed, 11 (50%) were polymorphic, with an average of 36.2% of the loci polymorphic within populations. Gene diversity measures for the species (Hes = 0.121) and for the populations (Hep = 0.099) were slightly higher than means found for other surveyed endemic plants. Compared to nine previously analyzed woody mints, however, M. alba is genetically depauperate. Little genetic structure was evident within the species, with 92% of the total genetic variation found within populations. Genetic identities between population pairs were high (mean I = 0.98). The perennial life habit of M. alba and long-distance pollination by bumblebees may contribute to t...
Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable p... more Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fall...
Researchers have long been focused on enriching Random Utility Models (RUMs) for a variety of rea... more Researchers have long been focused on enriching Random Utility Models (RUMs) for a variety of reasons, including to better understand behavior, to improve the accuracy of forecasts, and to test the validity of simpler model structures. While numerous useful enhancements exist, they tend to be discussed and applied independently from one another. This paper presents a practical, generalized model that
The sustained use of cookstoves that are introduced to reduce fuel use or air pollution needs to ... more The sustained use of cookstoves that are introduced to reduce fuel use or air pollution needs to be objectively monitored to verify the sustainability of these benefits. Quantifying stove adoption requires affordable tools, scalable methods and validated metrics of usage. We quantified the longitudinal patterns of chimney-stove use of 80 households in rural Guatemala, monitored with Stove Use Monitors (SUMs) during 32 months. We counted daily meals and days in use at each monitoring period and defined metrics like the percent stove-days in use (the fraction of days in use from all stoves and days monitored). Using robust Poisson regressions we detected small seasonal variations in stove usage, with peaks in the warm-dry season at 92% stove-days (95%CI: 87%,97%) and 2.56 average daily meals (95%CI: 2.40,2.74). With respect to these values, the percent stove-days in use decreased by 3% and 4% during the warm-rainy and cold-dry periods respectively, and the daily meals by 5% and 12% re...
Objective. Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the... more Objective. Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the immediate use of chemotherapy (CT) following a complete clinical response (CR) in patients with stage III-IV ovarian cancer. We wanted to evaluate our strategy of reserving second line (2nd line) chemotherapy to the time of clinical recurrence by determining PFS intervals following first, second, and third
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for d... more Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies. The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies. In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% ...
Land-use legacies are known to shape the diversity and distribution of plant communities, but we ... more Land-use legacies are known to shape the diversity and distribution of plant communities, but we lack an understanding of whether historical land use influences community responses to contemporary disturbances. Because human-modified landscapes often bear a history of multiple land-use activities, this contingency can challenge our understanding of land-use impacts on plant diversity. We address this contingency by evaluating how beta diversity (the spatial variability of species composition), an important component of regional biodiversity, is shaped by interactions between historical agriculture and prescribed fire, two prominent disturbances that are often coincident in terrestrial ecosystems. At three study locations spanning 450 km in the southeastern United States, we surveyed longleaf pine woodland understory plant communities across 232 remnant and post-agricultural sites with differing prescribed fire regimes. Our results demonstrate that agricultural legacies are a strong predictor of beta diversity, but the direction of this land-use effect differed among the three study locations. Further, although beta diversity increased with prescribed fire frequency at each study location, this effect was influenced by agricultural land-use history, such that positive fire effects were only documented among sites that lacked a history of agriculture at two of our three study locations. Our study not only highlights the role of historical agriculture in shaping beta diversity in a fire-maintained ecosystem but also illustrates how this effect can be contingent upon fire regime and geographic location. We suggest that interactions among historical and contemporary land-use activities may help to explain dissimilarities in plant communities among sites in human-dominated landscapes.
Background/Question/Methods The determinants of large-scale patterns of alpha and beta diversity ... more Background/Question/Methods The determinants of large-scale patterns of alpha and beta diversity are still poorly understood, especially as they relate to changes in diversity caused by historical and contemporary anthropogenic disturbance. Using the highly diverse understory plant communities found in longleaf pine savannas, we evaluate the contribution of historical and current land management practices in explaining alpha and beta diversity. Our sampling regime was conducted at 279 sites spread among three locations: Fort Bragg, NC, Fort Stewart, GA, and the Savanna River Site, SC. Locations spanned over 300km in the southeastern U.S. This unique combination of large-scale spatial extent and intensive within-location sampling provides a robust way to evaluate patterns of alpha and beta diversity. For each location, we stratified our sampling efforts across environmental and degradation gradients based on land use history (historical agricultural fields vs. remnant forests) and th...
To determine the response, toxicities, and progression free survival of a regimen of temsirolimus... more To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma. Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single age...
A panel of 14 physicians practicing medicine in the United States with expertise in radiology, ob... more A panel of 14 physicians practicing medicine in the United States with expertise in radiology, obstetrics and gynecology, gynecologic oncology, hysteroscopy, epidemiology, and pathology was convened by the Society of Radiologists in Ultrasound to discuss the role of sonography in women with postmenopausal bleeding. Broad objectives of this conference were (1) to advance understanding of the utility of different diagnostic techniques for evaluating the endometrium in women with postmenopausal bleeding; (2) to formulate useful and practical guidelines for evaluation of women with postmenopausal bleeding, specifically as it relates to the use of sonography; and (3) to offer suggestions for future research projects. October 24 and 25, 2000, Washington, DC, preceding the annual Society of Radiologists in Ultrasound Advances in Sonography conference. Specific questions to the panel included the following: (1) What are the relative effectiveness and cost-effectiveness of using transvaginal sonography versus office (nondirected) endometrial biopsy as the initial examination for a woman with postmenopausal bleeding? (2) What are the sonographic standards for evaluating a woman with postmenopausal bleeding? (3) What are the abnormal sonographic findings in a woman with postmenopausal bleeding? (4) When should saline infusion sonohysterography or hysteroscopy be used in the evaluation of postmenopausal bleeding? (5) Should the diagnostic approach be modified for patients taking hormone replacement medications, tamoxifen, or other selective estrogen receptor modulators? Consensus recommendations were used to create an algorithm for evaluating women with postmenopausal bleeding. All panelists agreed that because postmenopausal bleeding is the most common presenting symptom of endometrial cancer, when postmenopausal bleeding occurs, clinical evaluation is indicated. The panelists also agreed that either transvaginal sonography or endometrial biopsy could be used safely and effectively as the first diagnostic step. Whether sonography or endometrial biopsy is used initially depends on the physician's assessment of patient risk, the nature of the physician's practice, the availability of high-quality sonography, and patient preference. Similar sensitivities for detecting endometrial carcinoma are reported for transvaginal sonography when an endometrial thickness of greater than 5 mm is considered abnormal and for endometrial biopsy when "sufficient" tissue is obtained. Currently, with respect to mortality, morbidity, and quality-of-life end points, there are insufficient data to comment as to which approach is more effective. The conference concluded by identifying several important unanswered questions and suggestions that could be addressed by future research projects.
Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers... more Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study. This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participant's mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression. Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P…
Logit Kernel is a discrete choice model that has an i.i.d. extreme value (or Gumbel) additive dis... more Logit Kernel is a discrete choice model that has an i.i.d. extreme value (or Gumbel) additive disturbance à la multinomial logit as well as a flexible disturbance, which could be normal, additive, or otherwise. The result is an intuitive, practical, and powerful model that combines the flexibility of probit (and more) with the tractability of logit. For this reason, logit
Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding ... more Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs...
Proceedings of the National Academy of Sciences of the United States of America, Jan 8, 2015
To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical sa... more To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical samples spanning normalcy, increasingly severe cervical intraepithelial neoplasia (CIN1- CIN3), and cervical cancer (CxCa) from multiple perspectives, revealing a cascade of progressive changes. Compared with normal tissue, expression of many DNA replication/repair and cell proliferation genes was increased in CIN1/CIN2 lesions and further sustained in CIN3, consistent with high-risk human papillomavirus (HPV)-induced tumor suppressor inactivation. The CIN3-to-CxCa transition showed metabolic shifts, including decreased expression of mitochondrial electron transport complex components and ribosomal protein genes. Significantly, despite clinical, epidemiological, and animal model results linking estrogen and estrogen receptor alpha (ERα) to CxCa, ERα expression declined >15-fold from normalcy to cancer, showing the strongest inverse correlation of any gene with the increasing expression ...
Macbridea alba is a herbaceous perennial mint endemic to the panhandle region of Florida. We used... more Macbridea alba is a herbaceous perennial mint endemic to the panhandle region of Florida. We used starch gel electrophoresis to describe allozyme diversity and genetic structure in this federally threatened plant. Ten populations were analyzed, with an average sample size of 47 plants (range 41-48 plants) per population. Of the 22 loci analyzed, 11 (50%) were polymorphic, with an average of 36.2% of the loci polymorphic within populations. Gene diversity measures for the species (Hes = 0.121) and for the populations (Hep = 0.099) were slightly higher than means found for other surveyed endemic plants. Compared to nine previously analyzed woody mints, however, M. alba is genetically depauperate. Little genetic structure was evident within the species, with 92% of the total genetic variation found within populations. Genetic identities between population pairs were high (mean I = 0.98). The perennial life habit of M. alba and long-distance pollination by bumblebees may contribute to t...
Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable p... more Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fall...
Researchers have long been focused on enriching Random Utility Models (RUMs) for a variety of rea... more Researchers have long been focused on enriching Random Utility Models (RUMs) for a variety of reasons, including to better understand behavior, to improve the accuracy of forecasts, and to test the validity of simpler model structures. While numerous useful enhancements exist, they tend to be discussed and applied independently from one another. This paper presents a practical, generalized model that
The sustained use of cookstoves that are introduced to reduce fuel use or air pollution needs to ... more The sustained use of cookstoves that are introduced to reduce fuel use or air pollution needs to be objectively monitored to verify the sustainability of these benefits. Quantifying stove adoption requires affordable tools, scalable methods and validated metrics of usage. We quantified the longitudinal patterns of chimney-stove use of 80 households in rural Guatemala, monitored with Stove Use Monitors (SUMs) during 32 months. We counted daily meals and days in use at each monitoring period and defined metrics like the percent stove-days in use (the fraction of days in use from all stoves and days monitored). Using robust Poisson regressions we detected small seasonal variations in stove usage, with peaks in the warm-dry season at 92% stove-days (95%CI: 87%,97%) and 2.56 average daily meals (95%CI: 2.40,2.74). With respect to these values, the percent stove-days in use decreased by 3% and 4% during the warm-rainy and cold-dry periods respectively, and the daily meals by 5% and 12% re...
Objective. Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the... more Objective. Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the immediate use of chemotherapy (CT) following a complete clinical response (CR) in patients with stage III-IV ovarian cancer. We wanted to evaluate our strategy of reserving second line (2nd line) chemotherapy to the time of clinical recurrence by determining PFS intervals following first, second, and third
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for d... more Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies. The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies. In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% ...
Land-use legacies are known to shape the diversity and distribution of plant communities, but we ... more Land-use legacies are known to shape the diversity and distribution of plant communities, but we lack an understanding of whether historical land use influences community responses to contemporary disturbances. Because human-modified landscapes often bear a history of multiple land-use activities, this contingency can challenge our understanding of land-use impacts on plant diversity. We address this contingency by evaluating how beta diversity (the spatial variability of species composition), an important component of regional biodiversity, is shaped by interactions between historical agriculture and prescribed fire, two prominent disturbances that are often coincident in terrestrial ecosystems. At three study locations spanning 450 km in the southeastern United States, we surveyed longleaf pine woodland understory plant communities across 232 remnant and post-agricultural sites with differing prescribed fire regimes. Our results demonstrate that agricultural legacies are a strong predictor of beta diversity, but the direction of this land-use effect differed among the three study locations. Further, although beta diversity increased with prescribed fire frequency at each study location, this effect was influenced by agricultural land-use history, such that positive fire effects were only documented among sites that lacked a history of agriculture at two of our three study locations. Our study not only highlights the role of historical agriculture in shaping beta diversity in a fire-maintained ecosystem but also illustrates how this effect can be contingent upon fire regime and geographic location. We suggest that interactions among historical and contemporary land-use activities may help to explain dissimilarities in plant communities among sites in human-dominated landscapes.
Background/Question/Methods The determinants of large-scale patterns of alpha and beta diversity ... more Background/Question/Methods The determinants of large-scale patterns of alpha and beta diversity are still poorly understood, especially as they relate to changes in diversity caused by historical and contemporary anthropogenic disturbance. Using the highly diverse understory plant communities found in longleaf pine savannas, we evaluate the contribution of historical and current land management practices in explaining alpha and beta diversity. Our sampling regime was conducted at 279 sites spread among three locations: Fort Bragg, NC, Fort Stewart, GA, and the Savanna River Site, SC. Locations spanned over 300km in the southeastern U.S. This unique combination of large-scale spatial extent and intensive within-location sampling provides a robust way to evaluate patterns of alpha and beta diversity. For each location, we stratified our sampling efforts across environmental and degradation gradients based on land use history (historical agricultural fields vs. remnant forests) and th...
To determine the response, toxicities, and progression free survival of a regimen of temsirolimus... more To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma. Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single age...
A panel of 14 physicians practicing medicine in the United States with expertise in radiology, ob... more A panel of 14 physicians practicing medicine in the United States with expertise in radiology, obstetrics and gynecology, gynecologic oncology, hysteroscopy, epidemiology, and pathology was convened by the Society of Radiologists in Ultrasound to discuss the role of sonography in women with postmenopausal bleeding. Broad objectives of this conference were (1) to advance understanding of the utility of different diagnostic techniques for evaluating the endometrium in women with postmenopausal bleeding; (2) to formulate useful and practical guidelines for evaluation of women with postmenopausal bleeding, specifically as it relates to the use of sonography; and (3) to offer suggestions for future research projects. October 24 and 25, 2000, Washington, DC, preceding the annual Society of Radiologists in Ultrasound Advances in Sonography conference. Specific questions to the panel included the following: (1) What are the relative effectiveness and cost-effectiveness of using transvaginal sonography versus office (nondirected) endometrial biopsy as the initial examination for a woman with postmenopausal bleeding? (2) What are the sonographic standards for evaluating a woman with postmenopausal bleeding? (3) What are the abnormal sonographic findings in a woman with postmenopausal bleeding? (4) When should saline infusion sonohysterography or hysteroscopy be used in the evaluation of postmenopausal bleeding? (5) Should the diagnostic approach be modified for patients taking hormone replacement medications, tamoxifen, or other selective estrogen receptor modulators? Consensus recommendations were used to create an algorithm for evaluating women with postmenopausal bleeding. All panelists agreed that because postmenopausal bleeding is the most common presenting symptom of endometrial cancer, when postmenopausal bleeding occurs, clinical evaluation is indicated. The panelists also agreed that either transvaginal sonography or endometrial biopsy could be used safely and effectively as the first diagnostic step. Whether sonography or endometrial biopsy is used initially depends on the physician's assessment of patient risk, the nature of the physician's practice, the availability of high-quality sonography, and patient preference. Similar sensitivities for detecting endometrial carcinoma are reported for transvaginal sonography when an endometrial thickness of greater than 5 mm is considered abnormal and for endometrial biopsy when "sufficient" tissue is obtained. Currently, with respect to mortality, morbidity, and quality-of-life end points, there are insufficient data to comment as to which approach is more effective. The conference concluded by identifying several important unanswered questions and suggestions that could be addressed by future research projects.
Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers... more Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study. This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participant's mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression. Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P…
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Papers by Joan Walker