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1.
Am J Obstet Gynecol ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31401259

RESUMO

BACKGROUND: Endometrial intraepithelial neoplasia (EIN), also known as complex atypical hyperplasia (CAH), is a precancerous lesion of the endometrium associated with a 40% risk concurrent endometrial cancer at the time of hysterectomy. While a majority of endometrial cancers (EC) diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low-risk, low-stage, approximately 10% of patients ultimately diagnosed with EC will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, little data exists regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. OBJECTIVE: (s): 1) To determine if preoperative factors can predict the presence of concurrent endometrial cancer at time of hysterectomy in patients with endometrial intraepithelial neoplasia; 2) To describe the ability of preoperative characteristics to predict which patients may be at a higher risk of lymph node involvement requiring lymph node assessment at the time of hysterectomy. STUDY DESIGN: We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically-confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring LND. Unadjusted associations between covariates and progression to endometrial cancer were estimated through two-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. RESULTS: Of the 1055 charts reviewed, 169 patients were eligible and included. Eighty-seven (51.5%) patients had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease while eighty-two (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at time of hysterectomy (15.7 mm (SD = 9.5) vs 12.5 mm (SD = 6.4), p=0.01). Endometrial stripe of ≥ 2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% CI: (1.5-10.0)), controlling for age. 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe ≥ 2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe < 2 cm. CONCLUSIONS: Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥ 2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

2.
J Clin Oncol ; 37(26): 2317-2328, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31216226

RESUMO

PURPOSE: We report the final, protocol-specified analysis of overall survival (OS) in GOG-0218, a phase III, randomized trial of bevacizumab in women with newly diagnosed ovarian, fallopian tube, or primary peritoneal carcinoma. METHODS: A total of 1,873 women with incompletely resected stage III to IV disease were randomly assigned 1:1:1 to six 21-day cycles of intravenous carboplatin (area under the concentration v time curve 6) and paclitaxel (175 mg/m2) versus chemotherapy plus concurrent bevacizumab (15 mg/kg, cycles 2 to 6) versus chemotherapy plus concurrent and maintenance bevacizumab (cycles 2 to 22). Inclusion criteria included a Gynecologic Oncology Group performance status of 0 to 2 and no history of clinically significant vascular events or evidence of intestinal obstruction. OS was analyzed in the intention-to-treat population. A total of 1,195 serum and/or tumor specimens were sequenced for BRCA1/2 and damaging mutations in homologous recombination repair (HRR) genes. Intratumoral microvessel density was studied using CD31 immunohistochemistry. RESULTS: Median follow-up was 102.9 months. Relative to control (n = 625), for patients receiving bevacizumab-concurrent (n = 625), the hazard ratio (HR) of death was 1.06 (95% CI, 0.94 to 1.20); for bevacizumab-concurrent plus maintenance (n = 623), the HR was 0.96 (95% CI, 0.85 to 1.09). Disease-specific survival was not improved in any arm. No survival advantage was observed after censoring patients who received bevacizumab at crossover or as second line. Median OS for stage IV bevacizumab-concurrent plus maintenance was 42.8 v 32.6 months for stage IV control (HR, 0.75; 95% CI, 0.59 to 0.95). Relative to wild type, the HR for death for BRCA1/2 mutated carcinomas was 0.62 (95% CI, 0.52 to 0.73), and for non-BRCA1/2 HRR, the HR was 0.65 (95% CI, 0.51 to 0.85). BRCA1/2, HRR, and CD31 were not predictive of bevacizumab activity. CONCLUSION: No survival differences were observed for patients who received bevacizumab compared with chemotherapy alone. Testing for BRCA1/2 mutations and homologous recombination deficiency is essential.

3.
Gynecol Oncol ; 153(3): 496-499, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31230614

RESUMO

OBJECTIVES: To assess the performance sentinel lymph node (SLN) biopsy and effect of ultrastaging in clinically early stage endometrial cancer. METHODS: Patients with endometrial cancer prospectively enrolled after informed consent was obtained. The cervix was injected superficially with 1 mL of ISB and 1 mL of ICG (diluted 1:25) at 3 and 9 o'clock each. SLN biopsy was followed by complete pelvic lymphadenectomy (aortic lymphadenectomy at the discretion of the surgeon). Lymph nodes (LNs) were analyzed by standard sectioning with H&E; ultrastaging of SLN was done retrospectively and blinded to treating physicians. RESULTS: 204 patients received dye injections. In 184 (90.2%) patients at least one SLN was identified. Of all patients, 138 (68%) had bilateral mapping. In the patients with successful mapping of a hemipelvis, ICG detected SLNs in 83% and ISB in 64% of cases (p < 0.0001). Median BMI (kg/m2) for patients with successful mapping was 35.7 compared to 40.1 for those who did not map (p = 0.01). Twenty-three (11.3%) patients had positive LNs. Applying the SLN algorithm, positive nodes were detected in 21/23 (91.3%). The negative predictive value (NPV) was 98.9% (95% CI: 96.01% to 99.71%). Eleven patients had positive SLN with isolated tumor cells (ITCs) or micrometastases detected on ultrastaging. Including these patients, 34 (17%) had positive LNs, increasing the NPV to 99% and sensitivity to 94%. There were no recurrences in patients with ITCs only. CONCLUSIONS: SLN assessment in endometrial cancer is feasible and safe with high NPV (99%). ICG was more effective in detecting SLN compared to ISB. Although ultrastaging detected additional positive LNs, treatment based on standard sectioning appears reasonable but further research is needed.


Assuntos
Adenocarcinoma/secundário , Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Corantes , Neoplasias do Endométrio/cirurgia , Reações Falso-Negativas , Feminino , Humanos , Histerectomia , Verde de Indocianina , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Micrometástase de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Pelve , Valor Preditivo dos Testes , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos , Corantes de Rosanilina
5.
Clin Obstet Gynecol ; 62(3): 403-404, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30950864
6.
Gynecol Oncol ; 153(2): 255-258, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30718123

RESUMO

OBJECTIVE: The impact of pathologic features of a cone biopsy on the management of women with early stage cervical cancer is understudied. Our objective was to evaluate the additive value of pathologic features of a cone biopsy toward identifying patients with high risk tumors for which adjuvant therapy may be indicated. METHODS: Patients with early stage cervical cancer undergoing a conization followed by radical hysterectomy from 1995 to 2016 were retrospectively identified. Clinical and pathologic data were abstracted from patient medical records. RESULTS: A total of 115 patients were identified. Based on final pathology, 70.5% were low risk, 10.4% intermediate risk, and 19.1% were high risk. The additive pathologic features of the conization specimen would have reclassified five patients from low into the intermediate risk group. Though depth of invasion did not correlate with final pathology results, when lymphovascular space invasion (LVSI) was present in the conization specimen, 51.2% of patients were noted to meet intermediate/high risk; compared to only 9.5% without LVSI. CONCLUSIONS: In women with early stage cervical cancer, additive pathology of the conization and hysterectomy specimen did not significantly impact risk stratification, only affecting 4.3% of patients. However, presence of LVSI in the conization was associated with intermediate risk criteria in 60% of cases and high risk criteria in 37% of cases. As patients with intermediate/high risk criteria would meet recommendations for adjuvant therapy, the evaluation of LVSI in conization specimens may influence the selection of primary treatment for women with cervical cancer.


Assuntos
Colo do Útero/patologia , Conização , Histerectomia , Seleção de Pacientes , Neoplasias do Colo do Útero/patologia , Adulto , Colo do Útero/cirurgia , Quimiorradioterapia Adjuvante/métodos , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Neoplasias do Colo do Útero/terapia
7.
Clin Cancer Res ; 25(12): 3495-3507, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30804020

RESUMO

PURPOSE: This first-in-human phase I study (NCT01417546) evaluated the safety profile, optimal immunologic/biological dose (OID/OBD), and immunogenicity of the combination of two peptide B-cell epitope vaccines engineered to represent the trastuzumab- and pertuzumab-binding sites. Although trastuzumab and pertuzumab have been approved for clinical use, patients often develop resistance to these therapies. We have advanced a new paradigm in immunotherapy that focuses on humoral responses based on conformational B-cell epitope vaccines. PATIENTS AND METHODS: The vaccine is comprised of two chimeric HER-2 B-cell peptide vaccines incorporating a "promiscuous T-cell epitope." Patients were immunized with the vaccine constructs emulsified with nor-muramyl-dipeptide adjuvant in a water-in-oil Montanide ISA 720VG vehicle. Eligible patients with metastatic and/or recurrent solid tumors received three inoculations every 3 weeks. RESULTS: Forty-nine patients with a median of 4 prior lines of chemotherapy received at least 1 vaccination. Twenty-eight patients completed the 3 vaccination regimens. Six patients received 1 six-month boost after the regimen, and one patient received 7 six-month boosts. No serious adverse reactions or dose-limiting toxicities were observed. The vaccine was well tolerated with dose level 2 as the recommended phase II dose. The most common related toxicity in all patients was injection-site reactions (24%). Two patients had a partial response, 14 had stable disease, and 19 had progressive disease. CONCLUSIONS: The study vaccine is safe, exhibits antitumor activity, and shows preliminary indication that peptide vaccination may avoid therapeutic resistance and offer a promising alternative to monoclonal antibody therapies.

8.
Gynecol Oncol ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30503265

RESUMO

OBJECTIVES: Platinum hypersensitivity reactions (HSR) affect approximately 5% of the general oncologic population. Here we report the efficacy and safety of outpatient platinum desensitization protocol (PD) in gynecologic oncology patients with moderate (high-risk) to severe platinum HSR. METHODS: This is a retrospective report of patients with gynecologic malignancies undergoing an outpatient PD for moderate (high-risk) to severe platinum HSR from 2011 to 2017. Patient demographics, chemotherapy histories, and PD outcomes were collected. Descriptive statistics were performed given the exploratory nature of the study. RESULTS: Forty-eight patients meeting inclusion criteria were identified. Most patients were being treated for ovarian cancer (56.3%) and were receiving carboplatin during their initial platinum HSR (75.0%). Patients received a mean of 10.3 platinum doses prior to their initial HSR. Transient hypertension was the most common sign of moderate (high-risk) HSR while persistent tachycardia was the most common sign of severe HSR. A total of 295 PD cycles were attempted with a successful completion rate of 96.6%. The mean number of PD cycles received by patients was 5.1. Almost 65% of patients experienced breakthrough reactions but over 58% of these breakthrough reactions were isolated to the first PD cycle. Only 8.3% of patients had severe breakthrough reactions, all of whom initially underwent shortened desensitization. Of these 4 patients, 2 successfully underwent desensitization with a prolonged protocol. CONCLUSION: Outpatient PD is safe and effective in patients with gynecologic malignancies. This may present a feasible option for institutions with multi-disciplinary teams experienced with the management of platinum HSR.

9.
J Natl Cancer Inst ; 2018 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-30312457

RESUMO

Background: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. Methods: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. Results: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. Conclusion: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.

10.
Gynecol Oncol ; 151(3): 501-505, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30282591

RESUMO

OBJECTIVE: To assess compliance with, and outcomes related to, the Society of Gynecologic Oncology quality measure in ovarian cancer to administer chemotherapy within 42 days of cytoreductive surgery in patients with epithelial ovarian/fallopian tube/peritoneal cancer. METHODS: Institutional ovarian cancer database was evaluated for compliance with the quality measure to administer chemotherapy within 42 days of cytoreductive surgery. The influence of chemotherapy timing on the risk of death was evaluated, and factors related to the timing of chemotherapy after surgery was assessed. RESULTS: Of 668 patients with epithelial ovarian/fallopian tube/peritoneal cancer who underwent surgical treatment for their disease (primary or interval), 635 met criteria for administration of adjuvant chemotherapy (with stages IA/IB, grade 2 or 3 disease; stage IC or more advanced stage disease). Compliance to administer chemotherapy within 42 days was 59.1%. The adjusted risk of death was not strongly associated with time to chemotherapy within 42 days (aHR: 0.80; 0.61, 1.05) and this did not differ by primary or interval debulking surgery. CONCLUSIONS: In this prospectively maintained database, 59.1% of patients received chemotherapy within 42 days of surgery. The time to chemotherapy interval of within 42 days was not strongly associated with improved survival, particularly when age, stage of disease, insurance enrollment and surgical characteristics were taken into account. Further, the relationship between time to chemotherapy interval of within 42 days and survival did not vary by patients who received primary versus interval debulking surgery or had no residual disease.

11.
Am J Obstet Gynecol ; 219(3): 303.e1-303.e6, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29959932

RESUMO

BACKGROUND: While many studies have documented the high prevalence of burnout in practicing physicians and medical trainees, fewer reports describe burnout in academic leaders. In 2002, we observed a moderate-high to high level of burnout in 41.4% of chairs of academic departments of obstetrics and gynecology. OBJECTIVE: The purpose of this study was to identify trends in burnout and associated factors in today's obstetrics and gynecology chairs as they face complex changes to the current health care environment. STUDY DESIGN: This was a cross-sectional study. A survey was developed based on the questionnaire used in our first investigation and sent electronically to all members of the Council of University Chairs of Obstetrics and Gynecology. Burnout was measured using an abbreviated Maslach Burnout Inventory-Human Sciences Survey. In addition to demographic data, we assessed perceived stressors, job satisfaction, spousal/partner support, self-efficacy, depression, suicidal ideation, and stress management. RESULTS: The response rate was 60% (84/139). Almost 30% of chairs were women, increased from 7.6% in 2002. Hospital and department budget deficits and loss of key faculty remain major stressors noted by participants. The Maslach Burnout Inventory results have changed dramatically over the past 15 years. Today's chairs demonstrated less burnout but with an "ineffective" profile. Subscale scores for emotional exhaustion and depersonalization were reduced but >50% reported low personal accomplishment. Spousal support remained important in preventing burnout. CONCLUSION: Chairs of academic departments of obstetrics and gynecology continue to face significant job-related stress. Burnout has decreased; however, personal accomplishment scores have also declined most likely due to administrative factors that are beyond the chairs' perceived control.

12.
Gynecol Oncol Rep ; 25: 52-55, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29998182

RESUMO

Purpose: In this study we sought to: 1) determine rates of burnout and other associated indices of psychosocial distress such as alcohol and substance abuse, 2) establish the baseline performance of gynecologic oncologists on several positive psychology metrics, 3) determine if increased hope, resilience, and flourishing are associated with decreased burnout. Methods: A survey of members of the Society of Gynecologic Oncology (SGO) was conducted in spring of 2017. Participants were sent an electronic questionnaire consisting of 82 items measuring burnout, depression, substance abuse, flourishing, resilience, hope, and psychological wellbeing. Results: A total of 1745 members were invited and 374 (21.4%) responded. Overall, 23.0% of respondents scores above clinical cutoffs indicating burnout. Almost 50.0% of participants screened positive for depression, 17.0% screened positive for alcohol abuse and 12.0% screened positive for substance abuse. Respondents meeting criteria for burnout were more likely to screen positive for depression (p < .001) and substance abuse (p < .001). Participants not meeting criteria for burnout had higher resilience, flourishing, hope, and wellbeing scores (p < .001). Male respondents had higher levels of hope, resilience, and wellbeing while married participants had higher flourishing and wellbeing scores than their unmarried counterparts. Parents had higher levels of resilience and wellbeing compared to non-parents. Conclusions: Burnout and associated indices of physiological distress continue to affect a large segment of SGO membership. Participants not meeting the criteria for burnout had higher scores on resilience, flourishing, hope, and wellbeing metrics. This suggests new targets for evidence-based interventions to mitigate burnout among members of SGO.

13.
J Robot Surg ; 12(3): 517-521, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29285654

RESUMO

The objectives of the study were to describe robotic-assisted surgery training programs currently being used by ACGME-accredited obstetrics and gynecology (OB/Gyn) residency programs and to explore residents' attitudes towards their robotic surgery training curricula to evaluate resident desire for robotics training. We conducted a cross-sectional study of OB/Gyn residents for the 2015-2016 academic year. Participants completed a 31-item online questionnaire regarding their robotic-assisted surgical training and associated perspectives. Analyses of these data were primarily descriptive. In total, 98.9% of included respondents (N = 177) reported availability of a surgical robot at their training institution, and 35.0% of participants reported not having any structured robotics training program at their institution. The most commonly used training modalities included online modules (62.2%), dual-assist console (55.1%) and virtual reality simulation (50.3%). The most commonly reported barriers to completing a robots training were a lack of personal time (56.2%) and availability of the virtual reality simulator or access to the robotic equipment (29.2%). OB/Gyn residents desire robotics training and are exposed to a wide variety of training modalities. The ACGME should consider recommending the incorporation of a standardized formal robotics training program as part of the OB/Gyn residency curriculum.

14.
Gynecol Oncol ; 148(1): 49-55, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29174555

RESUMO

OBJECTIVE: Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions. METHODS: Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets. RESULTS: Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) (p<0.001), stage (p=0.009), CA125 (p<0.001), ascites (p<0.001), and stage-age interaction (p=0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI). CONCLUSIONS: We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool.


Assuntos
Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Modelos Estatísticos , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Idoso , Antígeno Ca-125/análise , Carcinoma Epitelial do Ovário , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Análise de Regressão
15.
Gynecol Oncol ; 146(3): 588-595, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28709704

RESUMO

OBJECTIVES: To determine the relationship between mismatch repair (MMR) classification and clinicopathologic features including tumor volume, and explore outcomes by MMR class in a contemporary cohort. METHODS: Single institution cohort evaluating MMR classification for endometrial cancers (EC). MMR immunohistochemistry (IHC)±microsatellite instability (MSI) testing and reflex MLH1 methylation testing was performed. Tumors with MMR abnormalities by IHC or MSI and MLH1 methylation were classified as epigenetic MMR deficiency while those without MLH1 methylation were classified as probable MMR mutations. Clinicopathologic characteristics were analyzed. RESULTS: 466 endometrial cancers were classified; 75% as MMR proficient, 20% epigenetic MMR defects, and 5% as probable MMR mutations. Epigenetic MMR defects were associated with advanced stage, higher grade, presence of lymphovascular space invasion, and older age. MMR class was significantly associated with tumor volume, an association not previously reported. The epigenetic MMR defect tumors median volume was 10,220mm3 compared to 3321mm3 and 2,846mm3, for MMR proficient and probable MMR mutations respectively (P<0.0001). Higher tumor volume was associated with lymph node involvement. Endometrioid EC cases with epigenetic MMR defects had significantly reduced recurrence-free survival (RFS). Among advanced stage (III/IV) endometrioid EC the epigenetic MMR defect group was more likely to recur compared to the MMR proficient group (47.7% vs 3.4%) despite receiving similar adjuvant therapy. In contrast, there was no difference in the number of early stage recurrences for the different MMR classes. CONCLUSIONS: MMR testing that includes MLH1 methylation analysis defines a subset of tumors that have worse prognostic features and reduced RFS.


Assuntos
Neoplasias do Endométrio/genética , Inativação Gênica , Proteína 1 Homóloga a MutL/genética , Recidiva Local de Neoplasia/genética , Fatores Etários , Idoso , Metilação de DNA , Reparo de Erro de Pareamento de DNA/genética , Intervalo Livre de Doença , Neoplasias do Endométrio/química , Neoplasias do Endométrio/patologia , Epigênese Genética , Feminino , Humanos , Metástase Linfática , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/análise , Mutação , Gradação de Tumores , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Carga Tumoral/genética
16.
Gynecol Oncol ; 146(3): 642-646, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28655413

RESUMO

OBJECTIVE: Physician burnout is associated with mental illness, alcohol abuse, and job dissatisfaction. Our objective was to estimate the impact of burnout on productivity of gynecologic oncologists during the first half of their career. METHODS: A decision model evaluated the impact of burnout on total relative value (RVU) production during the first 15years of practice for gynecologic oncologists entering the workforce from 2011 to 2015. The SGO practice survey provided physician demographics and mean annual RVUs. Published data were used to estimate probability of burnout for male and female gynecologic oncologists, and the impact of depression, alcohol abuse, and early retirement. Academic productivity was defined as annual PubMed publications since finishing fellowship. RESULTS: Without burnout, RVU production for the cohort of 250 gynecologic oncologists was 26.2 million (M) RVUs over 15years. With burnout, RVU production decreased by 1.6 M (5.9% decrease). Disproportionate rates of burnout among females resulted in 1.1 M lost RVUs for females vs. 488 K for males. Academic production without burnout was estimated at 9277 publications for the cohort. Burnout resulted in 1383 estimated fewer publications over 15years (14.9%). CONCLUSIONS: The impact of burnout on clinical and academic productivity is substantial across all specialties. As health care systems struggle with human resource shortages, this study highlights the need for effective burnout prevention and wellness programs for gynecologic oncologists. Unless significant resources are designated to wellness programs, burnout will increasingly affect the care of our patients and the advancement of our field.


Assuntos
Esgotamento Profissional/psicologia , Eficiência , Ginecologia , Modelos Estatísticos , Oncologistas/estatística & dados numéricos , Publicações Seriadas/estatística & dados numéricos , Alcoolismo/psicologia , Técnicas de Apoio para a Decisão , Depressão/psicologia , Feminino , Humanos , Masculino , Oncologistas/psicologia , Probabilidade , Escalas de Valor Relativo , Aposentadoria , Fatores Sexuais , Inquéritos e Questionários
18.
Gynecol Oncol ; 144(2): 290-293, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27884514

RESUMO

OBJECTIVE: Radical hysterectomy for cervical cancer is associated with increased morbidity over an extrafascial hysterectomy. The goal of this study was to determine incidence of and risk factors for parametrial involvement (PI) based on conization specimen (CS) and to potentially identify candidates for less radical surgery. METHODS: Patients with FIGO IA2-IIA cervical cancer treated with radical hysterectomy and pelvic lymph node dissection (RH) from 2000 to 2010 were retrospectively identified. Data was extracted from operative and pathology reports. Statistical analyses were performed using Fisher's exact test, t-test, and asymptotic logistic regression. RESULTS: Of 267 RH patients identified, 118 (44%) had conization prior to RH. The incidence of PI was 15.7% overall and 7.5% in patients treated with conization prior to RH. There was no association between PI and histology, stage, grade, or tumor size. Conization patients with PI were more likely to have LVSI on CS (77.8% vs. 29.4%) and positive lymph nodes (LNP) (66.7% vs. 8.3%). Of patients with positive endocervical curettage, a modest 12% had PI, which was not statistically significant. Tumor size, depth of invasion, and margin status on CS were not statistically associated with PI. In logistic regression analysis, LNP alone or LNP+LVSI were predictive of PI. CONCLUSIONS: The incidence of PI in early-stage cervical cancer is significant. Only LVSI on CS and LNP were predictors of PI in the current study. While there may be select patients with early stage cervical cancer who can be spared parametrectomy, additional research is warranted.


Assuntos
Conização , Histerectomia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
19.
J Colloid Interface Sci ; 490: 703-709, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-27978455

RESUMO

Physicochemical processes that take place at the oil-water interface of an epoxy-amine emulsion polymerisation system influence the properties and structural morphology of the polymeric microparticles formed. Investigating these processes, such as the transport of monomers across the liquid/liquid interface brings new understanding which can be used to tune polymeric morphology. Two different approaches are used to provide new insights on these processes. Microelectrochemical measurements at expanding droplets (MEMED) is used to measure the transfer of amine from an organic phase comprised of epoxide and amine into an aqueous receptor phase. The rate of amine transfer across the liquid/liquid interface is characterised using MEMED and finite element method modelling and kinetic values are reported. Time lapse microscopy of epoxide droplets held in deionised water or an aqueous amine solution heated to different temperatures is further used to characterise epoxide dissolution into the aqueous phase. Mass-transport of epoxide into the aqueous phase is shown to be temperature-dependent. Epoxide homopolymerisation at the droplet-water interface is found to influence the rate of epoxide droplet dissolution. The rate of the epoxy-amine cure reaction is shown to be faster than the rate of the epoxide homopolymerisation reaction. The combination of methods used here is not limited to emulsion polymerisation and should find application in a myriad of processes at liquid/liquid interfaces.

20.
Int J Gynecol Cancer ; 26(9): 1717-1721, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27575633

RESUMO

OBJECTIVE: This study aimed to compare outcomes of endometrial cancer (EMCA) staging in elderly patients performed either robotically or via laparotomy. METHODS: A retrospective, multi-institutional chart review was conducted of all robotic and laparotomy staging surgeries for EMCA between 2003 and 2009. Charts were reviewed for intraoperative and postoperative complications and morbidities. RESULTS: Seven hundred forty-six women were identified who had undergone EMCA staging either robotically or via laparotomy; 89 and 93 patients 70 years or older underwent staging for EMCA via robotic and laparotomy, respectively. Both groups had similar age and body mass index. Among elderly patients being staged robotically, a higher incidence of pelvic lymphadenectomy, and decreased blood loss, incidence of blood transfusion, and overall complications were seen compared to laparotomy. Postoperatively, elderly patients staged robotically had a shorter median hospital stay (1 vs 4 days, P < 0.001), with no increase in readmission or return to the operating theater. No vessel, bowel, or genitourinary injuries occurred. Vaginal cuff dehiscence after robotic surgery was not significantly different, but wound and fascial complications were significantly increased in patients undergoing laparotomy. Thromboembolism rates were similar between both groups. CONCLUSIONS: Elderly patients can safely undergo robotic EMCA staging with improved outcomes compared to laparotomy. The benefits of robotic staging include higher incidence of completion of lymphadenectomy, decreased hospital stay (without an increase in readmissions or reoperations), decreased transfusions, and decreased wound and fascial complications.


Assuntos
Neoplasias do Endométrio/cirurgia , Laparotomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Florida/epidemiologia , Humanos , Ohio/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
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