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1.
Gynecol Oncol ; 181: 54-59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134754

RESUMO

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos
2.
Obstet Gynecol ; 142(3): 708-724, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37543740

RESUMO

The Centers for Disease Control and Prevention sponsored a project conducted by the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. For this final module, focusing on the cancers of the lower anogenital tract (vulva, vagina, and anus), a panel of experts in evidence assessment from the Society for Academic Specialists in General Obstetrics and Gynecology, ASCCP, and the Society of Gynecologic Oncology reviewed relevant literature and current guidelines. Panel members conducted structured literature reviews, which were then reviewed by other panel members. Representatives from stakeholder professional and patient advocacy organizations met virtually in September 2022 to review and provide comment. This article is the executive summary of the review. It covers prevention, early diagnosis, and special considerations of lower anogenital tract cancer. Knowledge gaps are summarized to provide guidance for future research.


Assuntos
Neoplasias dos Genitais Femininos , Feminino , Humanos , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/prevenção & controle , Ginecologia , Obstetrícia , Especialização , Vulva , Literatura de Revisão como Assunto
3.
Gynecol Oncol ; 167(3): 429-435, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36244828

RESUMO

OBJECTIVES: To determine the clinical and prognostic significance of CA-125 trends prior to, during, and after chemotherapy in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients were enrolled in a phase III randomized trial (GOG 157) following upfront surgery for grade 3 stage IA/IB, stage IC, or stage II disease, and had been treated with either three or six cycles of carboplatin/paclitaxel. Kaplan-Meier method and Cox proportional hazards model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 350 patients, the median pre-chemotherapy CA-125 was 65 (IQR: 31-129). 71% of Whites had an elevated CA-125 compared to 47% of non-Whites (p = 0.006). Following the first cycle of chemotherapy, 74% of those with elevated CA-125 had normalization. Those who had normalization of CA-125 after 1 cycle had significantly better 5-year RFS (81% vs. 65%, p = 0.003) and OS (87% vs. 75%, p = 0.009) compared to those who did not normalize (defined as ≤35 U/mL). The pattern of CA-125 change following chemotherapy cycle 1, from normal to normal vs. elevated to normal vs. elevated to elevated had corresponding RFS of 87% vs. 80% vs. 68% (p = 0.013), and OS of 92% vs. 88% vs. 77% (p = 0.009). However, the percent decline (p = 0.993) and absolute nadir normal value of CA-125 (0-10 vs. 11-35 U/mL) were not predictive of outcome (p = 0.4). CONCLUSIONS: Normal baseline CA125 and normalization of this biomarker after the first cycle of chemotherapy were associated with better survival in high-risk early-stage epithelial ovarian cancer patients.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Antígeno Ca-125 , Carboplatina , Paclitaxel
5.
Obstet Gynecol ; 139(2): 157-162, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991145

RESUMO

OBJECTIVE: To assess the presentation, characteristics, and prognostic significance of symptoms in patients with high-risk early-stage epithelial ovarian cancer. METHODS: A retrospective chart review was performed on all patients enrolled in a phase III clinical trial (GOG 157). All patients had surgically staged, high-risk early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II). Chi-square and Kaplan-Meier estimates and Cox proportional hazards models were used for statistical analyses. RESULTS: Of 419 patients evaluated for symptoms, 301 (72%) presented with one or more symptoms, and 118 (28%) were asymptomatic but had a mass found on examination. Forty percent had only one symptom, and 32% had more than one symptom. Among those with at least one symptom, the most common were abdominal and pelvic pain (31%), and increased girth or fullness (26%). Overall, 23% of patients with tumors 10 cm or smaller, 27% of patients with tumors larger than 10 cm to 15 cm, and 46% of patients with tumors larger than 15 cm had multiple symptoms (P<.001). There was no significant difference in presentation of symptoms based on age, stage, or histologic subtype. Symptoms at diagnosis were not associated with recurrence or survival. CONCLUSION: More than 70% of patients with high-risk early-stage, epithelial ovarian cancer present with one or more symptoms, with the most common being abdominal or pelvic pain. The proportion of women with symptoms and the number of symptoms increase with enlarging tumor size.


Assuntos
Neoplasias Ovarianas/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
6.
Appl Immunohistochem Mol Morphol ; 30(1): 27-35, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34224438

RESUMO

We performed a pilot study in anticipation of using long-aged precut formalin-fixed paraffin-embedded tissue sections stored in real-world conditions for translational biomarker studies of topoisomerase 2A (TOP2A), Ki67, and human epidermal growth factor receptor 2 (HER2) in endometrial cancer. Formalin-fixed paraffin-embedded tissue blocks or unstained slides or both from GOG-0177 were collected centrally (1999-2000) and stored at room temperature. During 2004 to 2011 specimens were stored at 4°C. Matched pairs of stored slides and freshly cut slides from stored blocks were analyzed for TOP2A (KiS1), Ki67 (MIB1), and HER2 (HercepTest) proteins. To assess DNA stability (HER2 PathVision), fluorescence in situ hybridization (FISH) was repeated on stored slides from 21 cases previously shown to be HER2 amplified. Immunohistochemistry (IHC) staining intensity and extent, mean FISH copies/cell, and copy number ratios were compared using the κ statistic for concordance or signed rank test for differences in old cut versus new cut slides. IHC results reflected some protein degradation in stored slides. The proportion of cells with TOP2A staining was lower on average by 12% in older sections (P=0.03). The proportion of Ki67-positive cells was lower in stored slides by an average of 10% (P<0.01). Too few cases in the IHC cohort were FISH positive for any conclusions. HER2 amplification by FISH was unaffected by slide storage. We conclude that use of aged stored slides for proliferation markers TOP2A and Ki67 is feasible but may modestly underestimate true values in endometrial cancer. Pilot studies for particular storage conditions/durations/antigens to be used in translational studies are warranted.


Assuntos
Neoplasias da Mama , Neoplasias do Endométrio , Idoso , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Projetos Piloto , Receptor ErbB-2/metabolismo
7.
Gynecol Oncol Rep ; 38: 100889, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34926769

RESUMO

•We present an isolated skull metastasis in stage IB2 squamous cell carcinoma of the cervix.•Providers should have high index of suspicion for skull mass following cervical carcinoma diagnosis.•Adding denosumab to treatment regimen for bony metastasis should be considered due to its bone stabilizing properties.

8.
Am J Clin Pathol ; 155(6): 887-894, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33367493

RESUMO

OBJECTIVES: The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience. METHODS: Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute). RESULTS: Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as much as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients. CONCLUSIONS: Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.


Assuntos
Neoplasias/terapia , Satisfação do Paciente , Melhoria de Qualidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comunicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Patologistas , Encaminhamento e Consulta , Inquéritos e Questionários , Adulto Jovem
10.
Gynecol Oncol ; 158(2): 256-261, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32482336

RESUMO

OBJECTIVE: We aim to define national practice patterns to assess current clinical practice, anticipated delays and areas of concern that potentially could lead to deviations from the normal standard of care. METHODS: Anonymous surveys were emailed to members of the Society of Gynecologic Oncology (SGO). The spread of COVID-19 and its impact on gynecologic oncology care in terms of alterations to normal treatment patterns and anticipated challenges were assessed. The Wilcoxon rank sum test was performed to determine risk factors for COVID-19 infection. RESULTS: We analyzed the responses of 331 gynecologic oncology providers. COVID-19 is present in 99.1% of surveyed communities with 99.7% reporting mitigation efforts in effect. The infection rate differs significantly between regions (p≪0.001) with the Northeast reporting the highest number of COVID-19 cases. Practice volume has dropped by 61.6% since the start of the pandemic with most cancellations being provider initiated. A majority of responders (52.8%) believed that ovarian cancer will be the most affected cancer by COVID-19. >94% of responders are proceeding with gynecologic cancer surgeries with exception of grade 1, endometrioid endometrial adenocarcinoma (36.3%). Surgical backlog (58.6%), delayed cancer diagnosis (43.2%) and re-establishing normal care with delayed patient (37.8%) were identified as the top 3 challenges after COVID-19 has abated. CONCLUSIONS: COVID-19 is widespread and has radically altered normal practice patterns. Despite COVID-19 related concerns, most gynecologic oncology care is proceeding. However, the steep decline in clinical volume shows there is a large group of patients who are not being diagnosed or are deferring care.


Assuntos
Infecções por Coronavirus/epidemiologia , Neoplasias dos Genitais Femininos/terapia , Neoplasias dos Genitais Femininos/virologia , Pneumonia Viral/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Feminino , Humanos , Oncologia/métodos , Oncologia/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , SARS-CoV-2 , Oncologia Cirúrgica/métodos , Oncologia Cirúrgica/estatística & dados numéricos , Inquéritos e Questionários
11.
Gynecol Oncol ; 158(2): 236-243, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32532460

RESUMO

The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed.


Assuntos
Infecções por Coronavirus/prevenção & controle , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/virologia , Procedimentos Cirúrgicos em Ginecologia/métodos , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Oncologia Cirúrgica/métodos , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Tomada de Decisões , Feminino , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Controle de Infecções/normas , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , SARS-CoV-2 , Oncologia Cirúrgica/normas
12.
Gynecol Oncol ; 158(1): 16-24, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32386911

RESUMO

OBJECTIVES: The COVID-19 pandemic has consumed considerable resources and has impacted the delivery of cancer care. Patients with cancer may have factors which place them at high risk for COVID 19 morbidity or mortality. Highly immunosuppressive chemotherapy regimens and possible exposure to COVID-19 during treatment may put patients at additional risk. The Society of Gynecologic Oncology convened an expert panel to address recommendations for best practices during this crisis to minimize risk to patients from deviations in cancer care and from COVID-19 morbidity. METHODS: An expert panel convened to develop initial consensus guidelines regarding anti-neoplastic therapy during the COVID-19 pandemic with respect to gynecologic cancer care and clinical trials. RESULTS: COVID-19 poses special risks to patients who are older, have medical co-morbidities, and cancer. In addition, this pandemic will likely strain resources, making delivery of cancer care or conduct of clinical trials unpredictable. Recommendations are to limit visits and contact with health care facilities by using telemedicine when appropriate, and choosing regimens which require less frequent visits and which are less immunosuppressive. Deviations will occur in clinical trials as a result of limited resources, and it is important to understand regulatory obligations to trial sponsors as well as to the IRB to ensure that clinical trial and patient safety oversight are maintained. CONCLUSIONS: The ongoing crisis will strain resources needed to deliver cancer care. When alterations to the delivery of care are mandated, efforts should be taken to minimize risks and maximize safety while approximating standard practice.


Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/prevenção & controle , Neoplasias dos Genitais Femininos/terapia , Oncologia/métodos , Oncologia/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , COVID-19 , Infecções por Coronavirus/transmissão , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/virologia , Humanos , Pneumonia Viral/transmissão , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
13.
Cancer ; 126(12): 2775-2783, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32187665

RESUMO

BACKGROUND: Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression. METHODS: Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients: 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC. RESULTS: Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases. Mutations included those in PTEN, PIK3CA, and FGFR2, genes commonly mutated in EMC. Mutations in ARID1A and MYC were seen only in progressing hyperplasia, although these were uncommon; this limited diagnostic sensitivity. Progressing hyperplasia demonstrated an accumulation of mutations in oncogenic signaling pathways similarly to endometrial carcinoma. CONCLUSIONS: Because of mutational differences between progressing and nonprogressing hyperplasia, mutational analysis may predict the risk of progression from endometrial hyperplasia to EMC.


Assuntos
Carcinoma Endometrioide/genética , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/genética , Mutação , Adulto , Idoso , Carcinoma Endometrioide/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Estudos Retrospectivos , Fatores de Transcrição/genética , Adulto Jovem
14.
Gynecol Oncol ; 155(2): 283-286, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31519318

RESUMO

PURPOSE: The aim of our review was to ascertain factors associated with the successful completion of a randomized controlled trial in gynecological oncology. MATERIALS AND METHODS: This retrospective cohort study utilized data collected from the National Institutes of Health's US National Library of Medicine database on ClinicalTrials.gov. Data was collected over a five year period (2009-2013). Utilizing the search terms under the National Institutes of Health recommended "Studies by Topics" gynecological oncology studies were identified. Randomized controlled trials were selected for based on intervention and randomization criteria. Elements were then compared with statistical analysis performed using SASS. RESULTS: As of September 1st 2018, 149 of the 318 identified randomized controlled trials were successfully completed over a median length of 44 months (IQR 30.0-55.0). Completed randomized controlled trials were more likely to be performed at single centers (p < 0.005). Interventional, drug and device trials were not significantly more likely to be completed. There was no difference in funding sources for completed or not completed randomized controlled trials. CONCLUSIONS: Prospective randomized trials are essential for establishing the standard of care in clinical medicine. They are, however, time and resource intensive. Herein we have attempted to identify factors associated with successful and timely completion of gynecologic oncology randomized controlled trials including site of origin, number of participating sites, funding source, intervention type, enrollment size, and study length; however, none of these factors were observed to have an association with increased rates of trial publication.


Assuntos
Neoplasias dos Genitais Femininos/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Feminino , Neoplasias dos Genitais Femininos/economia , Humanos , Estudos Multicêntricos como Assunto/economia , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Estudos Prospectivos , Editoração/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Apoio à Pesquisa como Assunto , Estudos Retrospectivos
15.
Transl Oncol ; 12(10): 1289-1295, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325765

RESUMO

Nearly all cases of cervical cancer are initiated by persistent infection with high-risk strains of human papillomavirus (hr-HPV). When hr-HPV integrates into the host genome, the constitutive expression of oncogenic HPV proteins E6 and E7 function to disrupt p53 and retinoblastoma regulation of cell cycle, respectively, to favor malignant transformation. HPV E6 and E7 are oncogenes found in over 99% of cervical cancer, they are also expressed in pre-neoplastic stages making these viral oncoproteins attractive therapeutic targets. Monoclonal antibodies (mAbs) represent a novel potential approach against the actions of hr-HPV E6 and E7 oncoproteins. In this report, we describe the utilization of anti-HPV E6 and HPV E7 mAbs in an experimental murine model of human cervical cancer tumors. We used differential dosing strategies of mAbs C1P5 (anti-HPV 16 E6) and TVG701Y (anti-HPV E7) administered via intraperitoneal or intratumoral injections. We compared mAbs to the action of chemotherapeutic agent Cisplatin and demonstrated the capacity of mAbs to significantly inhibit tumor growth. Furthermore, we investigated the contribution of the immune system and found increased complement deposition in both C1P5 and TVG701Y treated tumors compared to irrelevant mAb therapy. Taken together, the results suggest that anti-HPV E6 and E7 mAbs exert inhibition of tumor growth in a viral-specific manner and stimulate an immune response that could be exploited for an additional treatment options for patients.

16.
Gynecol Oncol ; 154(1): 3-7, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30995961

RESUMO

George Papanicolaou, a Greek immigrant and cytopathologist, was responsible for what is now colloquially known as the "Pap smear"-undoubtedly one of the greatest advances in medicine and public health of the last century. However, his landmark research on the development of cervical cytology for the detection of precancerous lesions of the cervix ("New Cancer Diagnosis," 1928) made a rather inauspicious debut in an unlikely venue: John Harvey Kellogg's Third Race Betterment Conference-a meeting devoted to the furtherance of the concept and implementation of eugenics. Herein, we discuss the stark juxtaposition of Papanicolaou's landmark discovery amid the pseudoscience of the third Race Betterment Conference. We discuss the latency of Papnicolaou's discovery-its potential implications unrealized-until co-publication with Herbert Traut, which catapulted Papanicolaou's research to the scientific foreground. This gave rise to public health initiatives aimed at establishing the Pap smear as a screening tool. We further delineate the progress made in recent decades with the identification of HPV as the etiological agent for cervical cancer, and the subsequent development of the HPV vaccine, and discuss ongoing research in the present day. In this way, we hope to provide a background and historical context for the development of the Pap smear.


Assuntos
Teste de Papanicolaou/história , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal/história , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , História do Século XX , História do Século XXI , Humanos , Programas de Rastreamento/história , Programas de Rastreamento/tendências , Teste de Papanicolaou/tendências , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Estados Unidos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/tendências , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
17.
Gynecol Oncol ; 153(2): 335-342, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30827726

RESUMO

OBJECTIVES: The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients. METHODS: Surgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated. RESULTS: 361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables. CONCLUSION: SNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Endométrio/genética , Metástase Linfática/genética , Nucleosídeo NM23 Difosfato Quinases/genética , Idoso , Estudos de Casos e Controles , Progressão da Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Endométrio/patologia , Receptores ErbB/genética , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Prognóstico , Intervalo Livre de Progressão , Medição de Risco/métodos
18.
Redox Biol ; 25: 101051, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30509602

RESUMO

Ovarian cancer remains the most lethal gynecologic malignancy, and is primarily diagnosed at late stage when considerable metastasis has occurred in the peritoneal cavity. At late stage abdominal cavity ascites accumulation provides a tumor-supporting medium in which cancer cells gain access to growth factors and cytokines that promote survival and metastasis. However, little is known about the redox status of ascites, or whether antioxidant enzymes are required to support ovarian cancer survival during transcoelomic metastasis in this medium. Gene expression cluster analysis of antioxidant enzymes identified two distinct populations of high-grade serous adenocarcinomas (HGSA), the most common ovarian cancer subtype, which specifically separated into clusters based on glutathione peroxidase 3 (GPx3) expression. High GPx3 expression was associated with poorer overall patient survival and increased tumor stage. GPx3 is an extracellular glutathione peroxidase with reported dichotomous roles in cancer. To further examine a potential pro-tumorigenic role of GPx3 in HGSA, stable OVCAR3 GPx3 knock-down cell lines were generated using lentiviral shRNA constructs. Decreased GPx3 expression inhibited clonogenicity and anchorage-independent cell survival. Moreover, GPx3 was necessary for protecting cells from exogenous oxidant insult, as demonstrated by treatment with high dose ascorbate. This cytoprotective effect was shown to be due to GPx3-dependent removal of extracellular H2O2. Importantly, GPx3 was necessary for clonogenic survival when cells were cultured in patient-derived ascites fluid. While oxidation reduction potential (ORP) of malignant ascites was heterogeneous in our patient cohort, and correlated positively with ascites iron content, GPx3 was required for optimal survival regardless of ORP or iron content. Collectively, our data suggest that HGSA ovarian cancers cluster into distinct groups of high and low GPx3 expression. GPx3 is necessary for HGSA ovarian cancer cellular survival in the ascites tumor environment and protects against extracellular sources of oxidative stress, implicating GPx3 as an important adaptation for transcoelomic metastasis.


Assuntos
Progressão da Doença , Espaço Extracelular/metabolismo , Glutationa Peroxidase/metabolismo , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Antioxidantes/metabolismo , Ascite/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Células Clonais , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Estadiamento de Neoplasias , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
19.
Oncol Rev ; 12(1): 346, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29983902

RESUMO

Ovarian cancer is the leading cause of mortality among gynecologic malignancies, with most cases diagnosed at an advanced stage. Despite an initial response, most develop a recurrence and subsequent resistance to standard therapies. Pemetrexed (AlimtaTM) is a new generation multi-targeted antifolate initially approved for the treatment of malignant pleural mesothelioma. In recent years, it has shown promise in the treatment of recurrent epithelial ovarian cancer. In this review, we outline the current literature and discuss the future of pemetrexed in the setting of recurrent epithelial ovarian cancer.

20.
J Cancer Educ ; 33(1): 141-146, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27125832

RESUMO

The purpose of this study is to determine the association between gynecologic oncology fellowship training factors, including fellowship length, and a career in academic medicine. A survey was sent to all 980 gynecologic oncologists identified via the SGO membership directory. The survey questions focused on demographics, fellowship training, practice- type, and research involvement. Demographics of the study population and survey responses were reported using frequencies and percentages. Chi-squared tests were used to test for associations between selected survey responses and length of fellowship. The authors received 410 (42 %) responses. Most respondents (60 %) graduated from a 3-year fellowship, while 27 and 13 % attended 2- and 4-year fellowships, respectively. Practice descriptions included academic/university (52 %), community/private practice (21 %), private practice with academic appointment (20 %), and other (7 %). A majority (64 %) reported current involvement in research as a principal investigator (PI); however, 54 % reported spending 10 % or less of their time in research-related activities. Approximately half reported that their fellowship research experience contributed to their current practice. Graduates of 3- and 4-year fellowships had similar rates of employment in academic/university settings (58 and 52 %, respectively). Graduates of 4-year fellowships were more likely to hold an advanced degree and 11 or more publications at completion of fellowship. A majority of graduates of a gynecologic oncology fellowship practice in an academic/university setting and are involved in research. Fellowship length does not correlate with a current academic medicine appointment. Graduates of 4-year fellowships are more likely to hold additional advanced degrees and more publications.


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Pesquisa Biomédica , Escolha da Profissão , Bolsas de Estudo/estatística & dados numéricos , Ginecologia/educação , Oncologia/educação , Feminino , Humanos , Inquéritos e Questionários
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