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1.
J Natl Compr Canc Netw ; 22(3)2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38498974

RESUMO

BACKGROUND: The objective of this study was to evaluate the impact of Medicaid expansion on breast cancer treatment and survival among Medicaid-insured women in Ohio, accounting for the timing of enrollment in Medicaid relative to their cancer diagnosis and post-expansion heterogeneous Medicaid eligibility criteria, thus addressing important limitations in previous studies. METHODS: Using 2011-2017 Ohio Cancer Incidence Surveillance System data linked with Medicaid claims data, we identified women aged 18 to 64 years diagnosed with local-stage or regional-stage breast cancer (n=876 and n=1,957 pre-expansion and post-expansion, respectively). We accounted for women's timing of enrollment in Medicaid relative to their cancer diagnosis, and flagged women post-expansion as Affordable Care Act (ACA) versus non-ACA, based on their income eligibility threshold. Study outcomes included standard treatment based on cancer stage and receipt of lumpectomy, mastectomy, chemotherapy, radiation, hormonal treatment, and/or treatment for HER2-positive tumors; time to treatment initiation (TTI); and overall survival. We conducted multivariable robust Poisson and Cox proportional hazards regression analysis to evaluate the independent associations between Medicaid expansion and our outcomes of interest, adjusting for patient-level and area-level characteristics. RESULTS: Receipt of standard treatment increased from 52.6% pre-expansion to 61.0% post-expansion (63.0% and 59.9% post-expansion in the ACA and non-ACA groups, respectively). Adjusting for potential confounders, including timing of enrollment in Medicaid, being diagnosed in the post-expansion period was associated with a higher probability of receiving standard treatment (adjusted risk ratio, 1.14 [95% CI, 1.06-1.22]) and shorter TTI (adjusted hazard ratio, 1.14 [95% CI, 1.04-1.24]), but not with survival benefits (adjusted hazard ratio, 1.00 [0.80-1.26]). CONCLUSIONS: Medicaid expansion in Ohio was associated with improvements in receipt of standard treatment of breast cancer and shorter TTI but not with improved survival outcomes. Future studies should elucidate the mechanisms at play.


Assuntos
Neoplasias da Mama , Medicaid , Estados Unidos/epidemiologia , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Patient Protection and Affordable Care Act , Mastectomia , Ohio , Cobertura do Seguro
2.
J Natl Compr Canc Netw ; 22(2): 117-135, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38503056

RESUMO

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.


Assuntos
Neoplasias Vulvares , Feminino , Humanos , Adenocarcinoma/patologia , Neoplasias dos Genitais Femininos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/etiologia , Doença de Paget Extramamária/terapia , Neoplasias Cutâneas , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/etiologia
3.
Gynecol Oncol ; 178: 138-144, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37862793

RESUMO

OBJECTIVE: To analyze the impact of the early COVID-19 pandemic on the diagnosis and initiation of treatment for patients with gynecologic cancer. METHODS: Patients diagnosed with gynecologic cancer in the National Cancer Database during 2017-2020 were included. For the first aim, incidence rate ratios were calculated to compare gynecologic cancer diagnosis in the first year of the COVID-19 pandemic to the three years prior, and factors associated with a reduction in diagnosis were identified. For the second aim, patients who experienced an 8-week delay in cancer treatment were compared to those who did not. Multivariate logistic regression was used to identify factors associated with treatment delay. Propensity score analysis was utilized to compare the rate of cancer treatment delay in patients who were diagnosed with COVID-19 to those who were not. RESULTS: The incidence rate ratio of being diagnosed with gynecologic cancer in 2020 versus 2017-2019 was 0.90 (95%CI 0.90-0.91). Factors associated with increased risk of missed or delayed diagnosis in 2020 included cervical cancer, earlier cancer stage, younger age, lower levels of medical comorbidity, and lack of health insurance. In 2020, factors associated with treatment delay included COVID-19 diagnosis (aOR 1.50, 95%CI 1.35-1.67), in addition to race and ethnicity, insurance type, comorbidity, cancer stage, and primary site. The risk of treatment delay remained significantly elevated in patients diagnosed with COVID-19 after propensity-score matching. CONCLUSIONS: Gynecologic cancer diagnosis and timely provision of care were negatively impacted during the first year of the COVID-19 pandemic, with certain subgroups at elevated risk.


Assuntos
COVID-19 , Neoplasias dos Genitais Femininos , Neoplasias do Colo do Útero , Humanos , Feminino , COVID-19/epidemiologia , Pandemias , Teste para COVID-19 , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/terapia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia
4.
Cancer ; 129(24): 3915-3927, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37489821

RESUMO

BACKGROUND: Many studies compare state-level outcomes to estimate changes attributable to Medicaid expansion. However, it is imperative to conduct more granular, demographic-level analyses to inform current efforts on cancer prevention among low-income adults. Therefore, the authors compared the volume of patients with cancer and disease stage at diagnosis in Ohio, which expanded its Medicaid coverage in 2014, with those in Georgia, a nonexpansion state, by cancer site and health insurance status. METHODS: The authors used state cancer registries from 2010 to 2017 to identify adults younger than 64 years who had incident female breast cancer, cervical cancer, or colorectal cancer. Multivariable Poisson regression was conducted by cancer type, health insurance, and state to examine the risk of late-stage disease, adjusting for individual-level and area-level covariates. A difference-in-differences framework was then used to estimate the differences in risks of late-stage diagnosis in Ohio versus Georgia. RESULTS: In Ohio, the largest increase in all three cancer types was observed in the Medicaid group after Medicaid expansion. In addition, significantly reduced risks of late-stage disease were observed among patients with breast cancer on Medicaid in Ohio by approximately 7% and among patients with colorectal cancer on Medicaid in Ohio and Georgia after expansion by approximately 6%. Notably, the authors observed significantly reduced risks of late-stage diagnosis among all patients with colorectal cancer in Georgia after expansion. CONCLUSIONS: More early stage cancers in the Medicaid-insured and/or uninsured groups after expansion suggest that the reduced cancer burden in these vulnerable population subgroups may be attributed to Medicaid expansion. Heterogeneous risks of late-stage disease by cancer type highlight the need for comprehensive evaluation frameworks, including local cancer prevention efforts and federal health policy reforms. PLAIN LANGUAGE SUMMARY: This study looked at how Medicaid expansion affected cancer diagnosis and treatment in two states, Ohio and Georgia. The researchers found that, after Ohio expanded their Medicaid program, there were more patients with cancer among low-income adults on Medicaid. The study also found that, among people on Medicaid, there were lower rates of advanced cancer at the time of diagnosis for breast cancer and colon cancer in Ohio and for colon cancer in Georgia. These findings suggest that Medicaid expansion may be effective in reducing the cancer burden among low-income adults.


Assuntos
Neoplasias da Mama , Neoplasias do Colo , Adulto , Humanos , Feminino , Estados Unidos/epidemiologia , Medicaid , Patient Protection and Affordable Care Act , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Ohio/epidemiologia , Cobertura do Seguro , Políticas
5.
J Natl Compr Canc Netw ; 21(2): 181-209, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36791750

RESUMO

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Neoplasias Uterinas , Feminino , Humanos , Carcinoma Endometrioide/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patologia
6.
Mol Cancer Ther ; 22(5): 599-615, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36788429

RESUMO

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.


Assuntos
Proteína BRCA1 , Neoplasias Ovarianas , Feminino , Humanos , Proteína BRCA1/genética , Proteína Fosfatase 2/genética , Proteína BRCA2/genética , Dano ao DNA , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Recombinação Homóloga , Morte Celular
7.
Surg Endosc ; 37(5): 4000-4004, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36071261

RESUMO

BACKGROUND: Malignant bowel obstruction (MBO) is a sequela of advanced intraabdominal cancer and has a profound impact on quality of life. Common therapy is endoscopic decompressive gastrostomy tube placement. Standard gastrostomy tubes are poorly designed to completely evacuate the dependent portions of the stomach due to their location on the anterior gastric wall. In our institution we have begun placing the ASPIRE Assist gastrostomy tube (ASPIRE Bariatrics, Exton, PA) which includes a 15 cm long, 30Fr fenestrated gastric tube extension for enhanced gastric decompression. This tube is FDA indicated for gastric decompression and marketed for endoscopic weight loss. The purpose of this study is to review our experience managing MBO utilizing the ASPIRE Assist tube. METHODS: This is a retrospective analysis of outcomes at a single institution. All decompressive endoscopic gastrostomy tubes placed by two surgeons between November 2019 and July 2021 were reviewed. Endoscopic placement was performed utilizing standard safe tract and Ponsky pull techniques. RESULTS: Fourteen patients were identified (10F:4 M), mean age 70 (range 35-89). Primary cancer diagnoses included gynecologic (8), colorectal (3), bladder (1), small bowel (1), peritoneal serous (1). During the 12 months before decompressive gastrostomy tube placement, mean number of hospital admissions for MBO was 1.6 (range 1-3). Following tube placement, twelve patients had no further hospital admissions for MBO over their lifespan of mean 270 days (range 8-679 days). One patient had 1 admission for MBO in the 12 months before tube placement and 3 admissions in the 4 months after placement. A second patient had 2 admissions in the 12 months before tube placement and 1 admission in their 54-day lifespan after placement. There were no major complications. CONCLUSIONS: Endoscopic placement of the ASPIRE Assist gastrostomy tube is safe for palliation of MBO and may improve gastric decompression compared with standard endoscopic gastrostomy tubes. Enhanced gastric decompression can better manage symptoms, reduce hospital encounters, and improve quality of life. Further study is needed, however, our initial data appears promising.


Assuntos
Obstrução Intestinal , Neoplasias , Humanos , Feminino , Idoso , Estudos Retrospectivos , Qualidade de Vida , Estômago/cirurgia , Gastrostomia/métodos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Descompressão/efeitos adversos
8.
Cancer Med ; 12(4): 4773-4785, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36207994

RESUMO

BACKGROUND: The aim of this study is to evaluate the extent and associations with patient-reported disruptions to cancer treatment and cancer-related care during the COVID-19 pandemic utilizing nationally representative data. METHODS: This analysis uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults (age >18) who reported requiring current cancer treatment or other cancer-related medical care in the second half of 2020 were included. Estimated proportions of patients with self-reported changes, delays, or cancelations to cancer treatment or other cancer care due to the COVID-19 pandemic were calculated using sampling weights and associations with sociodemographic and other health-related variables were analyzed. RESULTS: In total, 574 (sample-weighted estimate of 2,867,326) adults reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. An estimated 32.1% reported any change, delay, or cancelation. On sample-weighted univariable analysis, patients who were younger, female, had one or fewer comorbidities, and uninsured were significantly more likely to report disruptions. On sample-weighted, multivariable analysis, patients who were younger and female remained significant predictors. Nearly 90% of patients included in the study reported virtual appointment use. Patients reporting disruptions were also significantly more likely to report feelings of anxiety. CONCLUSIONS: An estimated 1/3 of patients experienced disruptions to cancer care due to the COVID-19 pandemic. Patients experiencing disruptions in care were more likely to be female or younger which may reflect risk stratification strategies in the early stages of the pandemic, and also had higher rates of anxiety. The longitudinal impact of these disruptions on outcomes merits further study.


Assuntos
COVID-19 , Neoplasias , Adulto , Humanos , Feminino , Masculino , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Ansiedade/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Neoplasias/epidemiologia , Neoplasias/terapia
9.
Med Care ; 60(11): 821-830, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36098269

RESUMO

BACKGROUND: The mechanisms underlying improvements in early-stage cancer at diagnosis following Medicaid expansion remain unknown. We hypothesized that Medicaid expansion allowed for low-income adults to enroll in Medicaid before cancer diagnosis, thus increasing the number of stably-enrolled relative to those who enroll in Medicaid only after diagnosis (emergently-enrolled). METHODS: Using data from the 2011-2017 Ohio Cancer Incidence Surveillance System and Medicaid enrollment files, we identified individuals diagnosed with incident invasive breast (n=4850), cervical (n=1023), and colorectal (n=3363) cancer. We conducted causal mediation analysis to estimate the direct effect of pre- (vs. post-) expansion on being diagnosed with early-stage (-vs. regional-stage and distant-stage) disease, and indirect (mediation) effect through being in the stably- (vs. emergently-) enrolled group, controlling for individual-level and area-level characteristics. RESULTS: The percentage of stably-enrolled patients increased from 63.3% to 73.9% post-expansion, while that of the emergently-enrolled decreased from 36.7% to 26.1%. The percentage of patients with early-stage diagnosis remained 1.3-2.9 times higher among the stably-than the emergently-enrolled group, both pre-expansion and post-expansion. Results from the causal mediation analysis showed that there was an indirect effect of Medicaid expansion through being in the stably- (vs. emergently-) enrolled group [risk ratios with 95% confidence interval: 1.018 (1.010-1.027) for breast cancer, 1.115 (1.064-1.167) for cervical cancer, and 1.090 (1.062-1.118) for colorectal cancer. CONCLUSION: We provide the first evidence that post-expansion improvements in cancer stage were caused by an increased reliance on Medicaid as a source of stable insurance coverage.


Assuntos
Patient Protection and Affordable Care Act , Neoplasias do Colo do Útero , Adulto , Feminino , Humanos , Cobertura do Seguro , Medicaid , Ohio , Estados Unidos , Neoplasias do Colo do Útero/diagnóstico
10.
JCO Oncol Pract ; 18(5): e721-e730, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34995104

RESUMO

PURPOSE: To address challenges promoting tobacco cessation in oncology settings, it is important to understand characteristics associated with patient engagement in tobacco cessation treatment. This analysis examined predictors of participating in at least one tobacco cessation counseling session among patients referred to a comprehensive cancer center's Tobacco Intervention and Psychosocial Support (TIPS) service. METHODS: Patients with cancer who reported current smoking or recently quitting and referred to TIPS between June 2017 and February 2020 were included in the analysis. Independent variables included sex, race and ethnicity, insurance type, cancer diagnosis (tobacco-related or not), age, nicotine dependence, and cigarettes smoked per day at baseline. The outcome variable was completion of at least one tobacco cessation counseling session among those assessed by the TIPS program. Unadjusted and adjusted analyses tested associations between the independent variables and tobacco cessation counseling engagement. RESULTS: Of 360 oncology patients referred to the TIPS program, 224 (62.2%) were assessed and 120 (33%) engaged in at least one counseling session. After controlling for sociodemographics and tobacco use, the results demonstrated that patients diagnosed with tobacco-related cancers were 45.3% less likely to engage in the tobacco cessation program compared with those with non-tobacco-related cancers (P = .041). CONCLUSION: Patients diagnosed with tobacco-related cancers were less likely to engage in TIPS. Additional therapeutic resources may be needed to engage these patients to address potential explanatory factors, such as stigma, guilt, and fatalism. More research is needed to explore the impact of a tobacco-related cancer diagnosis on treatment engagement.


Assuntos
Neoplasias , Abandono do Hábito de Fumar , Abandono do Uso de Tabaco , Tabagismo , Aconselhamento/métodos , Demografia , Humanos , Neoplasias/epidemiologia , Neoplasias/psicologia , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , Tabagismo/terapia
13.
Support Care Cancer ; 28(5): 2311-2319, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31478164

RESUMO

PURPOSE: Incidence and mortality rates of uterine cancer are increasing and, obesity, which is also rising, has been associated with uterine cancer development and mortality. A recent study found that poor sleep quality is common among endometrial cancer survivors and those with obesity had more sleep disturbances than those having normal weight. However, it is unclear if higher levels of obesity (Class III, BMI ≥ 40 kg/m2), which are rising rapidly, are differentially associated with sleep as well as depression and quality of life in endometrial cancer survivors. METHODS: We evaluated sleep, depression, and quality of life in 100 Stage I endometrial cancer survivors with obesity seeking weight loss enrolled in a lifestyle intervention (NCT01870947) at baseline. RESULTS: The average age was 60 years and mean BMI was 42.1 kg/m2 with 58% having a BMI ≥ 40 kg/m2. Most survivors (72.3%) had poor sleep quality and most (71.2%) reported sleeping < 7 h/night. Survivors with class III compared with class I obesity had significantly more sleep disturbances and daytime dysfunction; and, those with poor sleep had higher depression and lower quality of life. Survivors with a BMI ≥ 50 kg/m2 (~ 25%) had the highest levels of depression and lowest physical and emotional well-being. CONCLUSIONS: Our results reveal that endometrial cancer survivors with class III compared with class I obesity have poorer sleep quality, higher depression, and lower quality of life. Given the rising rates of obesity and uterine cancer mortality, interventions to combat both obesity and poor sleep are needed.


Assuntos
Sobreviventes de Câncer/psicologia , Neoplasias do Endométrio/psicologia , Obesidade/psicologia , Obesidade/terapia , Sono/fisiologia , Índice de Massa Corporal , Depressão , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/complicações , Obesidade/fisiopatologia , Qualidade de Vida , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Redução de Peso , Programas de Redução de Peso
14.
J Grad Med Educ ; 11(6): 668-673, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31871567

RESUMO

BACKGROUND: Most value-based care educational interventions teach knowledge of cost but fail to recognize the interrelatedness of the Accreditation Council for Graduate Medical Education (ACGME) competencies of medical knowledge, patient care, practice-based learning and improvement, and systems-based practice. OBJECTIVE: We analyzed the impact on clinical decision-making of an educational curriculum that incorporated the spectrum of ACGME competencies. METHODS: Five didactic sessions for a gynecologic oncology fellowship were modified to incorporate cost- and value-based care considerations for each clinical topic addressed. After discussion, the group of fellows identified 1 high-value and 5 low-value practices to target for improvement. The fellows then undertook a chart audit of clinical decisions occurring for patients seen in the outpatient clinics. The frequency of low- and high-value practices was compared before and after the educational intervention. RESULTS: A total of 126 patients with a cervical cancer diagnosis were seen by participants in the outpatient setting during the entire observation period. After the intervention, the occurrence of 3 identified low-value practices was reduced by 13% to 33%, demonstrating modest effect sizes (effect size ϕ = 0.2-0.3). One high-value practice (smoking cessation counseling) increased 100% after a fellow-initiated quality improvement project was undertaken. Two low-value practices, including routine surveillance imaging, remained unchanged. CONCLUSIONS: Overlaying value-based concepts in didactic conference teaching resulted in measurable changes in decision-making behavior. Engaging learners in a subsequent, focused quality practice review served as a vital part of their educational experience and allowed us to assess learner competency in its practical application.


Assuntos
Bolsas de Estudo/métodos , Oncologia/educação , Abandono do Hábito de Fumar , Neoplasias do Colo do Útero/terapia , Assistência Ambulatorial/organização & administração , Tomada de Decisão Clínica , Aconselhamento , Currículo , Atenção à Saúde/economia , Educação de Pós-Graduação em Medicina/métodos , Feminino , Humanos , Oncologia/economia , Neoplasias do Colo do Útero/diagnóstico por imagem
15.
Cancer Res ; 79(16): 4242-4257, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31142515

RESUMO

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma-specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule-mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations. SIGNIFICANCE: This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development.See related commentary by Haines and Huang, p. 4009.


Assuntos
Neoplasias do Endométrio , Proteína Fosfatase 2/genética , Carcinogênese , Feminino , Humanos , Mutação , Recidiva Local de Neoplasia
16.
Gynecol Oncol ; 151(2): 202-207, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30174176

RESUMO

BACKGROUND: Chemo-radiation (chemoRT) has improved the overall survival for locally advanced cervical cancer (LACC) though women whose disease involves the para-aortic nodes (PAN) experience recurrence rates and worse survival outcomes compared to those without PAN involvement. This Phase I study determined if additional cycles of systemic chemotherapy could be safely added to extended field chemoRT in this population of patients. METHODS: Women with LACC and documented positive PAN were eligible for treatment. All women were treated with extended field radiation and brachytherapy and concurrent cisplatin 40 mg/m2 weekly for six weeks. Four to six weeks after completion of chemoRT, patients were treated with four cycles of paclitaxel 135 mg/m2 and escalating doses of carboplatin (Dose Level (DL) 1 = AUC 4, DL2 = AUC 5). RESULTS: Eleven women were entered on study and 9 were evaluable for dose limiting toxicities (DLT). Two women (1 in each of 2 DLs) did not complete chemoRT and so were not evaluable for DLT. Three women completed all 10 cycles at DL 1 with no DLTs. Six women were then treated at DL 2. For the 10 patients evaluable for response, the ORR was 60% (CR + PR). PFS and OS at 12 months were 60% and 90%, respectively. The predominant grade 3 or 4 acute toxicities were hematologic. There were no grade 5 events. CONCLUSION: Extended field chemoRT followed by paclitaxel 135 mg/m2 and carboplatin AUC 5 is feasible in women with LACC and positive PAN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
17.
Gynecol Obstet Invest ; 83(6): 546-551, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29705775

RESUMO

BACKGROUND: Minimally invasive surgery is the preferred approach for performing many gynecologic procedures. Occasionally, supraumbilical port placement may be preferable to optimize visibility and maneuverability although the risks of complications are less well characterized compared to umbilical entry. METHODS: We conducted a retrospective review of computed tomograms from 92 patients to evaluate the anatomic considerations for umbilical and supraumbilical port entry based on patient age, body mass index (BMI), parity, abdominal wall thickness, and distance to the great vessels. RESULTS: Supraumbilical entry was not associated with differences in distance to the great vessels compared to the umbilicus. However, supraumbilical location and BMI were associated with greater abdominal wall thickness. Age and BMI were associated with greater distance to the great vessels, while age was associated with thinner abdominal wall. Multiple linear regression confirmed independent effects of age and BMI. No association between parity and distance to retroperitoneal vessels was observed. CONCLUSION: Younger patients may be at increased risk for great vessel injury and pre-peritoneal insufflation. Obese patients may be at risk for pre-peritoneal insufflation, while patients with BMI < 30, particularly with a skin-to-aorta distance < 7 cm, may be at an increased risk for great vessel injury. Surgeons should consider these factors when considering supraumbilical port entry.


Assuntos
Fatores Etários , Índice de Massa Corporal , Complicações Intraoperatórias/etiologia , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Umbigo/anatomia & histologia , Parede Abdominal/anatomia & histologia , Parede Abdominal/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Paridade , Espaço Retroperitoneal , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Umbigo/cirurgia
18.
J Obstet Gynaecol Can ; 40(3): 304-309, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29032066

RESUMO

OBJECTIVE: No standardization of quality of operative reporting currently exists, and this represents a missed opportunity for communication among health care providers. This study proposed a method to improve operative notes by structuring the findings by six anatomical zones of the pelvis. Objective I was to validate the method of documenting six zones of the pelvis by using intraoperative photography. Objective II was to compare this method with dictations from operative reports created before introducing this method. METHODS: This retrospective cohort study evaluated pre- and post-intervention results of using six zones to guide operative reporting. Reports were collected from participating surgeons and were scored using a validated scoring tool. Each participant was taught to photograph six zones and use the zones in the operative report. Pre- and post-intervention cases were compared using generalized linear mixed models. RESULTS: Scores of study participants using the zones were significantly higher than those without (P <0.0001). Surgeons showed an ability to improve their reporting. The detail illustrated in the cases was qualitatively richer, and the anatomy within the six zones was referenced more frequently. CONCLUSION: Compared with reports without the technique, incorporating the six zones greatly enhances operative reporting and likely would improve communication among care providers. More reliable communication of intraoperative findings has the potential to enhance the value of laparoscopy greatly as a diagnostic tool across gynaecological subspecialties.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/normas , Laparoscopia/normas , Relatório de Pesquisa/normas , Comunicação , Feminino , Humanos , Pelve/patologia , Pelve/cirurgia , Estudos Retrospectivos
19.
Obstet Gynecol Int ; 2017: 1945801, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28203253

RESUMO

Background. The objective of this study was to determine whether female surgical residents underestimate their surgical abilities relative to males on a standardized test of laparoscopic skill. Methods. Twenty-six male and female general surgery residents and 25 female obstetrics and gynecology residents at two academic centers were asked to predict their score prior to undergoing the Fundamentals of Laparoscopic Surgery standardized skills exam. Actual and predicted score as well as delta values (predicted score minus actual score) were compared between residents. Multivariate linear regression was used to determine variables associated with predicted score, actual score, and delta scores. Results. There was no difference in actual score based on residency or gender. Predicted scores, however, were significantly lower in female versus male general surgery residents (25.8 ± 13.3 versus 56.0 ± 16.0; p < 0.01) and in female obstetrics and gynecology residents versus male general surgery residents (mean difference 20.9, 95% CI 11.6-34.8; p < 0.01). Male residents more accurately predicted their scores while female residents significantly underestimated their scores. Conclusion. Gender differences in estimating surgical ability exist that do not reflect actual differences in performance. This finding needs to be considered when structuring mentorship in surgical training programs.

20.
J Minim Invasive Gynecol ; 23(7): 1075-1082, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27449691

RESUMO

STUDY OBJECTIVES: To identify morphometric characteristics of obese patients that best predict pulmonary intolerance to robotic pelvic surgery using a novel method for quantifying adipose distribution. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Fifty-nine patients with endometrial cancer who underwent robotic hysterectomy and lymphadenectomy between April 2008 and May 2014 and also underwent perioperative computed tomography (CT) imaging within 1 year. INTERVENTION: Visceral fat volume (VFV) and subcutaneous fat volume (SFV) were quantified through waist circumference measurements along with average volume estimation of slices taken at 3 levels: mid-waist, L2-L3, and L4-L5. Mean and maximum values were obtained for intraoperative physiological data. MEASUREMENTS AND MAIN RESULTS: The patients' mean body mass index (BMI) was 34 (range, 20-59). Along with waist circumference, VFV and SFV quantified by CT at the mid-waist, L2-L3, and L4-L5 levels were all significant independent predictors for peak airway pressure (PAP; average and maximum) and plateau airway pressure (Pplat; average and maximum) on multivariate regression analysis after adjustment for age, ethnicity, diabetes, hypertension, pulmonary disease, smoking, obstructive sleep apnea, American Society of Anesthesiologists classification, and duration of anesthesia. Compared with the other CT parameters, L2-L3 VFV was the best predictor of average PAP (ß = 0.398; p = .002), maximum PAP (ß = 0.493; p < .001), average Pplat (ß = 0.536; p < .001), and maximum Pplat (ß = 0.573; p < .001). CONCLUSION: These novel CT morphometric measurements represent valid predictors of pulmonary intolerance to robotic surgery in obese patients. Of the measures analyzed, VFV at L2-L3 best predicts pulmonary tolerance in obese patients.


Assuntos
Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/cirurgia , Obesidade Abdominal , Procedimentos Cirúrgicos Robóticos , Tecido Adiposo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Carcinoma Endometrioide/diagnóstico por imagem , Estudos de Coortes , Neoplasias do Endométrio/diagnóstico por imagem , Feminino , Hospitais Universitários , Humanos , Histerectomia/métodos , Excisão de Linfonodo , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
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