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1.
Gynecol Oncol ; 189: 1-8, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38971004

RESUMEN

OBJECTIVES: Tissue banking procedures have evolved to keep pace with precision medicine, technology, emerging understanding of racial disparities, and regulatory requirements. However, there is little published guidance regarding strategies to create and maintain a successful biorepository. Our objective is to describe the infrastructure and protocols used by our Gynecologic Oncology Tissue Bank. METHODS: Our Tissue Bank was founded in 1992. In August 2022, internal funding was used to modernize the Tissue Bank. We hired three full-time employees, implemented universal screening of patients treated by gynecologic oncology faculty, updated consenting protocols, and standardized communication with providers. Tumor tissue, blood derivatives, ascites, and pleural fluid were collected from eligible, consenting patients and processed. Patient-derived cell lines and organoids were generated. For quality control purposes, one formalin-fixed, paraffin-embedded (FFPE) sample per tissue site was analyzed by a board-certified pathologist. All samples were labeled and tracked in an OpenSpecimen collection protocol and clinically annotated in a secure database. RESULTS: From August 2022 to October 2023, 227 patients (83% white, 15% Black, 1% Asian) were enrolled and 4249 specimens were collected. Adherent cell lines were generated from 15 patients with ovarian cancer and cell suspensions for organoid generation were collected from 46 patients with ovarian cancer. A recharge center was established to self-sustain the Tissue Bank. Samples have been shared with academic and commercial collaborators. CONCLUSIONS: Our Tissue Bank has enrolled a large number of diverse patients, collected numerous specimen types, and collaborated widely. The procedures described here provide guidance for other institutions establishing similar resources.

3.
Mol Cancer Res ; 21(11): 1234-1248, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37527178

RESUMEN

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The propensity for metastasis within the peritoneal cavity is a driving factor for the poor outcomes associated with this disease, but there is currently no effective therapy targeting metastasis. In this study, we investigate the contribution of stromal cells to ovarian cancer metastasis and identify normal stromal cell expression of the collagen receptor, discoidin domain receptor 2 (DDR2), that acts to facilitate ovarian cancer metastasis. In vivo, global genetic inactivation of Ddr2 impairs the ability of Ddr2-expressing syngeneic ovarian cancer cells to spread throughout the peritoneal cavity. Specifically, DDR2 expression in mesothelial cells lining the peritoneal cavity facilitates tumor cell attachment and clearance. Subsequently, omentum fibroblast expression of DDR2 promotes tumor cell invasion. Mechanistically, we find DDR2-expressing fibroblasts are more energetically active, such that DDR2 regulates glycolysis through AKT/SNAI1 leading to suppressed fructose-1,6-bisphosphatase and increased hexokinase activity, a key glycolytic enzyme. Upon inhibition of DDR2, we find decreased protein synthesis and secretion. Consequently, when DDR2 is inhibited, there is reduction in secreted extracellular matrix proteins important for metastasis. Specifically, we find that fibroblast DDR2 inhibition leads to decreased secretion of the collagen crosslinker, LOXL2. Adding back LOXL2 to DDR2 deficient fibroblasts rescues the ability of tumor cells to invade. Overall, our results suggest that stromal cell expression of DDR2 is an important mediator of ovarian cancer metastasis. IMPLICATIONS: DDR2 is highly expressed by stromal cells in ovarian cancer that can mediate metastasis and is a potential therapeutic target in ovarian cancer.


Asunto(s)
Receptor con Dominio Discoidina 2 , Neoplasias Ováricas , Femenino , Humanos , Receptor con Dominio Discoidina 2/genética , Receptor con Dominio Discoidina 2/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Fosforilación , Colágeno/metabolismo , Matriz Extracelular/metabolismo
4.
Commun Biol ; 6(1): 688, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37400526

RESUMEN

High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) < 3.5 years) and 16 were long-term (LT) survivors (OS > 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development.


Asunto(s)
Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Pronóstico , Variaciones en el Número de Copia de ADN
5.
Clin Cancer Res ; 29(13): 2466-2479, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37097615

RESUMEN

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status. CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.


Asunto(s)
Neoplasias Ováricas , Platino (Metal) , Humanos , Femenino , Platino (Metal)/uso terapéutico , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , Biomarcadores de Tumor/uso terapéutico
6.
Gynecol Oncol Rep ; 44: 101075, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36217326

RESUMEN

Objective: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients. Methods: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses were used to analyze differences between patients from PC-shortage vs not PC-shortage areas. Results: Among 217 ovarian cancer patients, 54.4 % lived in PC-shortage areas. They were more likely to have Medicaid or no insurance and live in rural areas with higher poverty rates, significantly further from the treating cancer center and its affiliated hospital. Nevertheless, 49.2 % of patients from PC-shortage areas lived in urban communities. Residing in a PC-shortage area was not associated with increased surgical or medical complications, ICU admission, or hospital readmission, but was linked to more frequent prolonged hospitalization (26.3 % vs 14.1 %, p = 0.04). PC-shortage did not impact progression-free or overall survival. Conclusions: Patients from PC-shortage areas may require longer inpatient perioperative care in order to achieve the same 30-day postoperative outcomes as patients who live in non-PC shortage areas. Community access to PC is a critical factor to better understanding and reducing disparities among ovarian cancer patients.

7.
Gynecol Oncol ; 167(3): 496-501, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36180305

RESUMEN

OBJECTIVES: Visceral adiposity has been established as a predictor of outcomes in various cancers. We aimed to determine the association of radiographic measurements of visceral fat with clinical outcomes in patients with endometrial cancer. METHODS: A retrospective review of patients with stage III-IV endometrial cancer who underwent surgery between 2004 and 2014 was performed. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT;VAT+SAT) were assessed on preoperative computed tomography (CT) scans. Exploratory analysis was performed to establish the optimal cut-off values for VAT, SAT, and TAT to identify patients with poor prognostic body composition. Survival rates were analyzed using Kaplan-Meier analysis, log-rank tests, and cox-regression. RESULTS: Eighty-three patients were included. Forty-two (51%) patients had a low VAT/SAT ratio (<0.45) and 41 (49.4%) had a high VAT/SAT ratio (>0.45). There were no significant differences in demographics between the groups. The mean VAT, SAT, and TAT were 176.3 cm2, 379.3 cm2, and 555.3 cm2 respectively. Compared to patients with low VAT/SAT ratios, patients with high VAT/SAT ratios had a shorter recurrence-free survival (median 29.6 vs 32.3 months, P = 0.01) and shorter overall survival (median 56 vs 93.7 months, P = 0.03). CONCLUSIONS: Visceral fat measurements are predictive of outcomes in patients with advanced stage endometrial cancer. Specifically, VAT to SAT ratios are predictive of overall survival. Future studies should be pursued to identify potential therapeutic targets and biological mechanisms that underlie obesity's relationship with endometrial cancer.


Asunto(s)
Neoplasias Endometriales , Grasa Intraabdominal , Humanos , Femenino , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/metabolismo , Grasa Subcutánea/diagnóstico por imagen , Composición Corporal , Tomografía Computarizada por Rayos X , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/metabolismo
8.
Mol Cancer Ther ; 21(8): 1348-1359, 2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35588308

RESUMEN

Chemotherapy is often ineffective in advanced-stage and aggressive histologic subtypes of endometrial cancer. Overexpression of the receptor tyrosine kinase AXL has been found to be associated with therapeutic resistance, metastasis, and poor prognosis. However, the mechanism of how inhibition of AXL improves response to chemotherapy is still largely unknown. Thus, we aimed to determine whether treatment with AVB-500, a selective inhibitor of GAS6-AXL, improves endometrial cancer cell sensitivity to chemotherapy particularly through metabolic changes. We found that both GAS6 and AXL expression were higher by immunohistochemistry in patient tumors with a poor response to chemotherapy compared with tumors with a good response to chemotherapy. We showed that chemotherapy-resistant endometrial cancer cells (ARK1, uterine serous carcinoma and PUC198, grade 3 endometrioid adenocarcinoma) had improved sensitivity and synergy with paclitaxel and carboplatin when treated in combination with AVB-500. We also found that in vivo intraperitoneal models with ARK1 and PUC198 cells had decreased tumor burden when treated with AVB-500 + paclitaxel compared with paclitaxel alone. Treatment with AVB-500 + paclitaxel decreased AKT signaling, which resulted in a decrease in basal glycolysis. Finally, multiple glycolytic metabolites were lower in the tumors treated with AVB-500 + paclitaxel than in tumors treated with paclitaxel alone. Our study provides strong preclinical rationale for combining AVB-500 with paclitaxel in aggressive endometrial cancer models.


Asunto(s)
Antineoplásicos , Neoplasias Endometriales , Antineoplásicos/farmacología , Neoplasias Endometriales/metabolismo , Femenino , Glucólisis , Humanos , Paclitaxel , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo
9.
Gynecol Oncol Rep ; 39: 100928, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35024405

RESUMEN

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on referral to and delivery of gynecologic oncology care at a National Cancer Institute-designated Comprehensive Cancer Center. METHODS: We conducted a retrospective cohort study of patients referred for evaluation by a gynecologic oncologist at Washington University in St. Louis from October 2019 - February 2020 (pre-COVID-19), and April - August 2020 (COVID-19). The primary outcome, time from referral to evaluation by a gynecologic oncologist, was compared between the two time periods. Secondary outcomes included time from initial evaluation to treatment and delays/interruptions in care due to the pandemic. Sub-group analyses were performed on patients with a cancer diagnosis to evaluate the impact of COVID-19 on treatment decision making. RESULTS: 884 patients were referred during the study period. Total referrals fell by 32% (526 to 358 patients, p < 0.001) and referrals for cancer fell by 18% (228 to 188 patients, p = 0.049). The pandemic did not impact time from referral to initial gynecologic oncology appointment overall (pre-COVID-19: 19.1 vs. COVID-19: 17.4 days, p = 0.315) or among patients with cancer (14.4 vs. 13.9 days, p = 0.662). Time from initial appointment to cancer treatment decreased by 9 days (34 days to 25 days, p = 0.001). CONCLUSION: Referrals to gynecologic oncology decreased significantly during the early months of COVID-19. Though time from referral to evaluation was not impacted by the pandemic, time to treatment initiation decreased despite institutional changes related to COVID-19.

10.
Mol Cancer Res ; 20(2): 265-279, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34670865

RESUMEN

Over 80% of women with high-grade serous ovarian cancer (HGSOC) develop tumor resistance to chemotherapy and die of their disease. There are currently no FDA-approved agents to improve sensitivity to first-line platinum- and taxane-based chemotherapy or to PARP inhibitors. Here, we tested the hypothesis that expression of growth arrest-specific 6 (GAS6), the ligand of receptor tyrosine kinase AXL, is associated with chemotherapy response and that sequestration of GAS6 with AVB-S6-500 (AVB-500) could improve tumor response to chemotherapy and PARP inhibitors. We found that GAS6 levels in patient tumor and serum samples collected before chemotherapy correlated with ovarian cancer chemoresponse and patient survival. Compared with chemotherapy alone, AVB-500 plus carboplatin and/or paclitaxel led to decreased ovarian cancer-cell survival in vitro and tumor burden in vivo. Cells treated with AVB-500 plus carboplatin had more DNA damage, slower DNA replication fork progression, and fewer RAD51 foci than cells treated with carboplatin alone, indicating AVB-500 impaired homologous recombination (HR). Finally, treatment with the PARP inhibitor olaparib plus AVB-500 led to decreased ovarian cancer-cell survival in vitro and less tumor burden in vivo. Importantly, this effect was seen in HR-proficient and HR-deficient ovarian cancer cells. Collectively, our findings suggest that GAS6 levels could be used to predict response to carboplatin and AVB-500 could be used to treat platinum-resistant, HR-proficient HGSOC. IMPLICATIONS: GAS6/AXL is a novel target to sensitize ovarian cancers to carboplatin and olaparib. Additionally, GAS6 levels can be associated with response to carboplatin treatment.


Asunto(s)
Daño del ADN/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Clasificación del Tumor , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología
11.
Cancers (Basel) ; 13(23)2021 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-34884986

RESUMEN

Endometrial cancer remains the most prevalent gynecologic cancer with continued rising incidence. A less common form of this cancer is uterine serous cancer, which represents 10% of endometrial cancer cases. However, this is the most aggressive cancer. The objective was to assess whether inhibiting the receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve response in uterine serous cancer. To prove this, we conducted multiple angiogenesis assays including tube formation assays and angiogenesis invasion assays. In addition, we utilized mouse models with multiple cells lines and subsequently analyzed harvested tissue through immunohistochemistry CD31 staining to assess microvessel density. The combination treatment arms demonstrated decreased angiogenic potential in each assay. In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis.

12.
Gynecol Oncol ; 161(3): 700-704, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33648746

RESUMEN

OBJECTIVE: To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients. METHODS: A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancers between 1998 and 2015. The impact of frailty status at cancer diagnosis on overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: In this cohort (n = 1336) the median age at diagnosis was 74 (range 65-97). Nine hundred sixty-two (72%) women were Caucasian and 132 (10%) were African-American. Overall, 651(49%) of patients were considered frail. On multivariate analysis, frail patients had a 48% increased risk for death (aHR 1.48; 95% CI 1.29-1.69; P < 0.0001). Each 10% increase in frailty index was associated with a 16% increased risk of death (aHR, 1.16; 95% CI, 1.11 to 1.21; P < 0.0001). In subgroup analyses of the varying cancer types, the association of frailty status with prognosis was fairly consistent (aHR 1.15-2.24). The DAFI was more prognostic in endometrial (aHR 1.76; 95% CI 1.41-2.18, P < 0.0001) and vaginal/vulvar (aHR 1.94; 95% CI 1.34-2.81, P = 0.0005) cancers as well as patients with loco-regional disease (aHR 1.94; 95% CI 1.62-2.33, P < 0.0001). CONCLUSIONS: Frailty appears to be a significant predictor of mortality in gynecologic cancer patients regardless of chronological age. This measure of functional age may be of particular utility in women with loco-regional disease only who otherwise would have a favorable prognosis.


Asunto(s)
Anciano Frágil , Fragilidad , Neoplasias de los Genitales Femeninos/mortalidad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Etnicidad , Femenino , Neoplasias de los Genitales Femeninos/etnología , Humanos , Medicare , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Programa de VERF , Análisis de Supervivencia , Estados Unidos
13.
Gynecol Oncol Rep ; 35: 100694, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33490354

RESUMEN

It is unclear if surveillance for postmenopausal women with medically inoperable stage 1 endometrial cancer (EC) should differ depending on their management strategy. Thus, we investigated the utility of surveillance endometrial sampling among 53 postmenopausal women with medically inoperable, clinical stage I, grade 1 endometrioid EC who received either progestin therapy or radiation between 2009 and 2018, at a single academic institution. Frequency and results of endometrial sampling, as well as recurrence and survival rates were studied. Of 53 patients, 18 (34.0%) received progestin therapy and 35 (66.0%) radiation. Medically managed patients were treated with megestrol acetate (27.7%), a levonorgestrel intrauterine device (27.7%), or both (44.4%). Radiated patients were mostly treated with high-dose rate brachytherapy only (77.1%). Surveillance endometrial sampling (median procedures = 4, range 1-10) was strictly adhered to among all patients who received progestin therapy, but infrequently (6/35, 17.1%) performed among radiated patients, yielding no positive results. Three recurrences occurred over the median follow-up of 38 months. Two (11%) women in the progestin therapy group recurred locally and were diagnosed by endometrial sampling. One (3%) patient in the radiation group recurred distally in the lung 25.3 months after completing brachytherapy. We conclude that appropriate surveillance for women with medically inoperable, clinical stage I, grade 1 EC depends on the management strategy. For those treated with progestins, surveillance with endometrial sampling every 3-6 months can reveal local recurrence. However, given the excellent local control after radiation, endometrial sampling may not be warranted for women treated with definitive radiation.

14.
Gynecol Oncol ; 160(1): 312-321, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33257014

RESUMEN

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in women with gynecologic malignancies. This practice statement provides clinical data and overall quality of evidence regarding the use of direct oral anticoagulants (DOACs) in this patient population. Specifically, it reviews patient selection, safety measures, and nuances of perioperative use of these medications. The scope of this document is limited to DOAC use in gynecologic oncology rather than a broad discussion of VTE prophylaxis and management in general. The following recommendations and examination of extant data are based on DOAC trials conducted primarily in mixed populations with different cancer subtypes. Many of these trials include few, or no, women with gynecologic cancer. However, because there is very limited data in gynecologic cancer-specific populations, the results of these studies represent the best available evidence to support treatment recommendations in our patients. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee believe that the results of these studies may be extrapolated, with caution, to VTE treatment and prophylaxis for patients with gynecologic cancer.


Asunto(s)
Anticoagulantes/administración & dosificación , Neoplasias de los Genitales Femeninos/sangre , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Ginecología/normas , Oncología Médica/normas , Tromboembolia Venosa/tratamiento farmacológico , Femenino , Neoplasias de los Genitales Femeninos/patología , Ginecología/métodos , Humanos , Oncología Médica/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia Venosa/patología
15.
Gynecol Oncol ; 157(1): 287-292, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32001077

RESUMEN

OBJECTIVES: There are limited methods to identify which obese patients will experience wound complications after undergoing gynecologic surgery. We sought to determine the association between frailty and postoperative wound complications and to develop a prediction model for wound complications in this patient population. METHODS: We reviewed prospectively collected data of obese patients undergoing laparotomy though midline vertical incisions from 7/2013-3/2016. Modified frailty index (mFI) was calculated using 11 comorbidities previously validated. The primary outcome was the composite rate of postoperative wound complication. Data was analyzed using Fisher exact test or Chi-square and t-tests or Kruskal-Wallis tests. Poisson regression models were used to generate relative risks. Prediction models were created with receiver-operator characteristic curve analysis. RESULTS: Of 163 patients included, 56 (34%) were considered frail. Wound complications occurred in 52 patients (31.9%): 28 (50%) frail and 24 (22.4%) non-frail patients (RR 2.23, 95%CI 1.29-3.85). Frail patients had significantly greater frequencies of wound breakdown (37.5% vs 15%, RR 2.51, 95%CI 1.31-4.81). After controlling for BMI, tobacco use, and maximum postoperative glucose, frailty remained an independent predictor of wound complication (aRR 1.88, 95%CI 1.04-3.40). The area under the curve for the predictive model incorporating frailty was 0.73 for wound complications. CONCLUSION: Frailty is associated with wound complications in obese patients undergoing gynecologic surgery via a midline vertical incision and is a useful tool in identifying the most high risk patients. Further prospective research is necessary to incorporate mFI into preoperative planning and counseling.


Asunto(s)
Neoplasias de los Genitales Femeninos/cirugía , Obesidad/fisiopatología , Dehiscencia de la Herida Operatoria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Fragilidad/complicaciones , Fragilidad/fisiopatología , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/patología , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Laparotomía/efectos adversos , Laparotomía/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Obesidad/complicaciones , Estudios Retrospectivos , Adulto Joven
16.
Obstet Gynecol ; 133(4): 658-665, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30870300

RESUMEN

OBJECTIVE: To assess the rate of wound complications and evaluate the effectiveness of antibiotic prophylaxis in vulvar wide local excision procedures. METHODS: We performed a single-institution, retrospective cohort study of women undergoing vulvar surgery for premalignant lesions between January 2007 and January 2017. The primary outcome was a composite wound complication rate that included breakdown or infection within 8 weeks postoperatively. Data were analyzed using Fisher exact or χ test, Student t-test, and Poisson regression. RESULTS: Wound complications occurred in 154 (28.7%) of the 537 patients. Mean age was 52 years; most patients were white (83.1%), cigarette smokers (65.2%), had no prior vulvar treatment (54.4%), and had a preoperative diagnosis of high-grade squamous intraepithelial lesion (vulvar HSIL) (70.0%). The presence of other predisposing factors was similar between groups. In multivariate analysis, smoking (odds ratio [OR] 1.64, 95% CI 1.14-2.38) and primary rather than repeat vulvar surgery (OR 1.99, 95% CI 1.31-3.01) were associated with increased risk for wound complications. There was no significant difference in wound complications between women who received preoperative antibiotics and those who did not (30.4% vs 27.4%, P=.45), although the mean length of wound separation in the antibiotic group was shorter (1 vs 2 cm, P=.03). CONCLUSION: Wound complications are common among women undergoing surgery for vulvar HSIL, and interventional trials are warranted to evaluate the role of smoking cessation and prophylactic antibiotics to reduce postoperative morbidity.


Asunto(s)
Profilaxis Antibiótica/estadística & datos numéricos , Lesiones Precancerosas/cirugía , Infección de la Herida Quirúrgica/epidemiología , Neoplasias de la Vulva/cirugía , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Fumar/efectos adversos , Infección de la Herida Quirúrgica/prevención & control
17.
Obstet Gynecol Clin North Am ; 46(1): 179-197, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30683263

RESUMEN

The integration of palliative care and hospice into standard gynecologic oncology care is associated with cost-savings, longer survival, lower symptom burden, and better quality of life for patients and caregivers. Consequently, this comprehensive approach is formally recognized and endorsed by the Society of Gynecologic Oncology, the National Comprehensive Cancer Network, and the American Society of Clinical Oncology. This article reviews the background, benefits, barriers, and most practical delivery models of palliative care. It also discusses management of common symptoms experienced by gynecologic oncology patients.


Asunto(s)
Continuidad de la Atención al Paciente/normas , Neoplasias de los Genitales Femeninos/terapia , Cuidados Paliativos/normas , Transferencia de Pacientes/normas , Enfermo Terminal , Continuidad de la Atención al Paciente/economía , Femenino , Neoplasias de los Genitales Femeninos/mortalidad , Humanos , Cuidados Paliativos/economía , Transferencia de Pacientes/economía , Guías de Práctica Clínica como Asunto , Calidad de la Atención de Salud , Calidad de Vida
18.
Clin Cancer Res ; 25(8): 2366-2368, 2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30692101

RESUMEN

The tumor-specific immune response in endometrial cancer is variable within molecular subtypes. Thus, the tumor immune response offers a novel biomarker, separate from molecular subtypes, to predict which patients might respond to immunotherapy.See related article by Talhouk et al., p. 2537.


Asunto(s)
Neoplasias Endometriales , Inmunoterapia , Biomarcadores , Femenino , Humanos , Factores Inmunológicos
19.
Gynecol Oncol ; 152(2): 416-425, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30409489

RESUMEN

Epithelial ovarian cancer (EOC) is the leading cause of death due to gynecologic malignancy. The majority of advanced stage EOC patients, even those who respond well to frontline therapy, will ultimately recur and succumb to their disease. In platinum-sensitive EOC patients, or those who recur ≥6 months from initial diagnosis, treatment of recurrent disease has traditionally consisted of repeat platinum-based chemotherapy. Secondary cytoreduction remains controversial. Due to recent advances in molecularly targeted treatment options, outcomes for advanced stage EOC patients are significantly improving and hold great promise. This review discusses pivotal trials establishing platinum-based combination chemotherapy as the standard of care and addresses the utility of increasing a patient's platinum-free interval. It then discusses the role of anti-angiogenesis therapeutics, specifically bevacizumab, cediranib, and trebananib and their side effects. Lastly, it reviews key trials for the three poly-adenosine diphosphate [ADP]-ribose polymerases (PARP) inhibitors that have been FDA-approved for maintenance therapy in platinum-sensitive recurrent EOC: olaparib, rucaparib, and niraparib. This review concludes with a discussion regarding ongoing and future clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Femenino , Humanos , Compuestos Organoplatinos/administración & dosificación
20.
Gynecol Oncol Rep ; 23: 24-27, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29326973

RESUMEN

•Choroid metastases are extremely rare in endometrial cancer.•Choroid metastases can present as many different eye complaints.•Comprehensive eye exams are important in patients with visual complaints.

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