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OBJECTIVES: The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS: A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS: Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS: Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.
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Perda Sanguínea Cirúrgica , Transfusão de Sangue , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Humanos , Feminino , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Estudos Retrospectivos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/sangue , Transfusão de Sangue/estatística & dados numéricos , Pessoa de Meia-Idade , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Idoso , Adulto , Hemoglobinas/análise , Fatores de RiscoRESUMO
Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such as Tp53 and Pten However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressor Fbxw7 in endometrial cancer through defined genetic model systems. Inactivation of Fbxw7 and Pten resulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquired Trp53 mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial-mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.
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Neoplasias do Endométrio/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Neoplasias Uterinas/metabolismo , Animais , Movimento Celular , Proliferação de Células , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Endométrio/patologia , Células Epiteliais , Feminino , Humanos , Camundongos , Mutação , PTEN Fosfo-Hidrolase/metabolismo , Fenótipo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: To evaluate awareness and acceptability of population-based BRCA testing among an unselected population of women presenting for annual gynecologic health assessment, with secondary objective to determine if a racial disparity exists in acceptability and awareness of this screening strategy. METHODS: Women presenting for routine gynecologic care in an outpatient setting of a single academic institution were anonymously surveyed. Survey collected age, self-identified race and ethnicity, education level, personal and family history of breast and/or ovarian cancer (BOC), awareness and interest, and willingness to pay out of pocket for testing. Responses were compared with bivariate and multivariate analysis. RESULTS: Interest in testing was expressed in 150 of 301 (45.1%) of participants. Women with a family history of BOC were more likely to be interested in testing than those without (ORâ¯=â¯1.9 (1.0-3.6)). Interest in testing was associated willingness to pay (ORâ¯=â¯3.3 (1.7-6.4)). Higher education level was associated with awareness of testing (ORâ¯=â¯9.9 (2.0-49.7)). Interest in testing was similar between racial groups, but awareness and willingness to pay for testing were higher among White women. Multivariate analysis with adjustment for education level confirmed that Black and Hispanic women were less likely to have awareness of genetic testing compared to White women and non-Hispanic Women, respectively (ORâ¯=â¯0.11 (0.05-0.3); ORâ¯=â¯0.10 (0.01-0.8)). CONCLUSIONS: Interest in genetic testing among women in the general population is high. Despite interest, awareness of BRCA is poor among Black and Hispanic women even when adjusting for education level.
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Predisposição Genética para Doença , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Genes BRCA1 , Genes BRCA2 , Testes Genéticos/economia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Programas de Rastreamento/economia , Pessoa de Meia-Idade , População Branca/estatística & dados numéricosRESUMO
OBJECTIVE: Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective. METHODS: A cost-effectiveness analysis using a Markov model with a 7-month time horizon comparing (1) 3cycles of NACT with carboplatin and paclitaxel (CT), followed by interval cytoreductive surgery, then 3 additional cycles of CT, or (2) PCS followed by 6cycles of CT. Input parameters included probability of chemotherapy complications, surgical complications, treatment completion, treatment costs, and utilities. Model outcomes included costs, life-years gained, quality-adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratios (ICER), in terms of cost per life-year gained and cost per QALY gained. We accounted for differences in surgical complexity by incorporating the cost of additional procedures and the probability of undergoing those procedures. Probabilistic sensitivity analysis (PSA) was performed via Monte Carlo simulations. RESULTS: NACT resulted in a savings of $7034 per patient with a 0.035 QALY increase compared to PCS; therefore, NACT dominated PCS in the base case analysis. With PSA, NACT was the dominant strategy more than 99% of the time. CONCLUSIONS: In the short-term, NACT is a cost-effective alternative compared to PCS in women with AEOC. These results may translate to longer term cost-effectiveness; however, data from randomized control trials continues to mature.
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Procedimentos Cirúrgicos de Citorredução/economia , Neoplasias Epiteliais e Glandulares/economia , Neoplasias Ovarianas/economia , Idoso , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante/economia , Análise Custo-Benefício , Feminino , Humanos , Cadeias de Markov , Terapia Neoadjuvante/economia , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: Cervical excision procedures are essential to the care of cervical dysplasia and malignancy. We sought to determine whether learner involvement in cervical excision procedures affects the quality of excision specimen. MATERIALS AND METHODS: A retrospective cohort study of cervical cancer patients diagnosed from July 1, 2000, to July 1, 2015, was performed. We included patients who had (1) a cervical excision procedure, either loop electrosurgical excision procedure or cold knife cone, and (2) pathologic information available. Primary outcome was the margin status of the specimen; secondary outcome was the size of the excision specimen including both width and depth. The exposure of interest was trainee participation, defined as resident physicians under the supervision of either a gynecologist or gynecologic oncologist. Descriptive statistics and general linear models were used for analysis. RESULTS: Ninety-four patients were identified. Overall, 58% (n = 54) of procedures were performed with trainee involvement. There was no difference in age, body mass index, or specimen width between trainee-performed and nontrainee-performed excisions. There was no significant difference in the status of margins with or without a trainee [44/57 (77%) and 29/37 (78%), respectively, p = .89]. There was a statistically significant difference in median specimen depth between trainee-performed and nontrainee-performed cases (15.4 mm vs 12 mm, p < .02). When adjusting for age, body mass index, excision type, indication, presence of trainee, and type of supervising physician, only the indication and type of excision were associated with greater depth of excision, (p < .01). CONCLUSIONS: Trainee involvement in cervical excision procedures does not alter the quality of excision specimen.
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Margens de Excisão , Preceptoria/métodos , Qualidade da Assistência à Saúde , Procedimentos Cirúrgicos Operatórios/educação , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To determine if the time interval between excision procedure and definitive minimally invasive surgery (MIS) for cervical cancer impacts 30-day postoperative complications. METHODS: A retrospective cohort of patients diagnosed with cervical cancer from January 2000 to July 2015 was evaluated. Patients who underwent a cervical excision procedure followed by definitive MIS within 90days were included. Early definitive surgery was defined as ≤6 weeks following excision procedure, while delayed was defined as 6weeks to 3months. The primary outcome was 30-day complications. Statistical analysis included descriptive statistics and modified Poission regression. RESULTS: Overall, 138 patients met inclusion criteria. Of these, 33% (n=46) had early definitive surgery and 67% (n=92) had delayed definitive surgery. Median age was 42years (range 23-72years) and median BMI was 28kg/m2 (range 16-50kg/m2). Within demographic and surgical factors collected, only smoking status differed between groups with those in the delayed surgery group more likely to be non-smokers than those in the early surgery group (p=0.04). When adjusting for relevant demographic and surgical factors, patients in the early group were twice as likely to have 30-day complication (aRR 2.6, 95%CI 1.14-5.76, p=0.02). Evaluating only women who underwent a radical procedure, 30-day complications remained higher in the early surgery group (RR 2.56; 95%CI 1.22-5.38, p=0.01). CONCLUSIONS: Performing definitive MIS for cervical cancer within 6weeks after cervical excision is associated with increased risk for 30-day complications. Providers should consider delaying definitive surgical procedures for at least 6weeks following excision to reduce surgical complications.
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Colo do Útero/cirurgia , Histerectomia/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Fatores de TempoRESUMO
OPINION STATEMENT: Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment in endometrial cancer (EMCA). Unfortunately, full lymphadenectomy bears significant surgical and postoperative risks. The majority of patients with clinical stage I disease will not have metastatic disease; thus, a full lymphadenectomy only increases morbidity in this population of patients. The use of the sentinel lymph node (SLN) biopsy has emerged as an alternative to complete lymphadenectomy in EMCA. By removing the highest yield lymph nodes, the SLN biopsy has the same diagnostic ability as lymphadenectomy while minimizing morbidity. The sensitivity of sentinel lymph node identification with robotic fluorescence imaging for detecting metastatic endometrial and cervical cancer (FIRES) trial published this year is the largest prospective, multi-institution trial investigating the accuracy of the SLN biopsy for endometrial and cervical cancer. Results of this trial found an excellent sensitivity (97.2%) and false negative rate (3%) with the technique. The conclusions from the FIRES trial and those of a recent meta-analysis are that SLN biopsy has an acceptable diagnostic accuracy in detecting lymphatic metastases, and can replace lymphadenectomy for this diagnostic purpose. There remains controversy surrounding the SLN biopsy in high-risk disease and the use of adjuvant therapy in the setting of low volume disease detected with ultrastaging. Current data suggests that the technique is accurate in high-risk disease and that the increased detection of metastasis helps guide adjuvant therapy such that oncologic outcomes are likely not affected by forgoing a full lymphadenectomy. Further prospective study is needed to investigate the impact of low volume metastatic disease on oncologic outcomes and the need for adjuvant therapy in these patients.
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Neoplasias do Endométrio/diagnóstico , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Gerenciamento Clínico , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/terapia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Metástase Linfática , Morbidade , Biópsia de Linfonodo Sentinela/efeitos adversos , Biópsia de Linfonodo Sentinela/métodos , Padrão de CuidadoRESUMO
STUDY OBJECTIVE: To confirm the safety and feasibility outcomes of robotic radical parametrectomy and pelvic lymphadenectomy and compare the clinicopathological features of women requiring adjuvant treatment with the historical literature. DESIGN: Retrospective cohort study and review of literature (Canadian Task Force classification II-2). SETTING: Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill. PATIENTS: All patients who underwent robotic radical parametrectomy with upper vaginectomy (RRPV), and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy at our institution between January 2007 and December 2015. INTERVENTIONS: RRPV and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy. We also performed a literature review of the literature on radical parametrectomy after occult cervical carcinoma. MEASUREMENTS AND MAIN RESULTS: Seventeen patients with invasive carcinoma of the cervix discovered after extrafascial hysterectomy underwent RRPV with bilateral pelvic lymphadenectomy. There were 2 intraoperative complications, including 1 bowel injury and 1 bladder injury. One patient required a blood transfusion of 2 units. Three patients underwent adjuvant treatment with chemoradiation with radiation-sensitizing cisplatin. One of these patients had residual carcinoma on the upper vagina, 1 patient had positive parametria and pelvic nodes, and 1 patient had positive pelvic lymph nodes. No patients experienced recurrence, and 1 patient died from unknown causes at 59.4 months after surgery. We analyzed 15 studies reported in the literature and found 238 women who underwent radical parametrectomy; however, no specific preoperative pathological features predicted outcomes, the need for adjuvant treatment, or parametrial involvement. CONCLUSION: RRPV is a feasible and safe treatment option. As reflected in the literature, RRPV can help avoid empiric adjuvant chemoradiation; however, no pathological features predict the need for adjuvant treatment after surgery.
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Histerectomia/métodos , Excisão de Linfonodo/métodos , Peritônio/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Vagina/cirurgia , Colpotomia/efeitos adversos , Colpotomia/métodos , Feminino , Humanos , Histerectomia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Metástase Linfática , Recidiva Local de Neoplasia/cirurgia , Pelve/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
OBJECTIVE: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer. METHODS: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01). CONCLUSIONS: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication.
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Hipoalbuminemia/patologia , Infecção da Ferida Cirúrgica/sangue , Neoplasias Vulvares/sangue , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Hipoalbuminemia/sangue , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/patologia , Neoplasias Vulvares/patologia , Adulto JovemRESUMO
INTRODUCTION AND HYPOTHESIS: Women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI) frequently undergo more than one treatment prior to settling on their final strategy. We hypothesize that women who are younger, with worse POP and SUI symptoms will desire and choose surgical treatment. METHODS: A retrospective cohort study was performed over 1 year identifying new patients presenting with POP and/or SUI at a university hospital. Our aim was to determine patient desire for either surgical or conservative treatment, as well as the actual treatment chosen and received after the first visit and 1 year later. To identify predictors of choice, baseline demographic characteristics were obtained. RESULTS: Of the 203 women who met the inclusion criteria, 44.3 % (90/203) desired surgery and 55.7 % (113/203) desired conservative treatment at their first visit. Women who desired surgery were more likely to be younger (p = 0.003), sexually active (p = 0.001), have more advanced prolapse (p = 0.006), and have more bothersome symptoms (p = 0.05). Of the women who desired surgery at their first visit, 12.2 % (11/90) actually chose conservative treatment. These women were less likely to be insured (p = 0.01). By 1 year, of the women who initially desired and subsequently chose conservative treatment, 26.5 % (30/113) had undergone surgery. The women who changed from conservative to surgical treatment were more likely to be younger (p = 0.01), non-White (p = 0.03), and sexually active (p = 0.04). CONCLUSIONS: In this study, younger, sexually active women were more likely to either opt for surgery initially or to change their treatment plan from conservative to surgical.
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Tratamento Conservador , Preferência do Paciente , Prolapso de Órgão Pélvico/cirurgia , Incontinência Urinária por Estresse/cirurgia , Fatores Etários , Idoso , Comportamento de Escolha , Feminino , Humanos , Seguro Saúde , Pessoa de Meia-Idade , Preferência do Paciente/etnologia , Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença , Comportamento Sexual , Incontinência Urinária por Estresse/complicações , Incontinência Urinária por Estresse/terapiaRESUMO
OBJECTIVE: Robotic gynecological surgery is feasible in obese patients, but there remain concerns about the safety of this approach because the positioning required for pelvic surgery can exacerbate obesity-related changes in respiratory physiology. The objective of our study was to evaluate pulmonary and all-cause complication rates in obese women undergoing robotic gynecological surgery and to assess variables that may be associated with complications. STUDY DESIGN: A retrospective chart review was performed on obese patients (body mass index of ≥30 kg/m(2)) who underwent robotic gynecological surgery at 2 academic institutions between 2006 and 2012. The primary outcome was pulmonary complications and the secondary outcome was all-cause complications. Univariate and multivariate logistic regression analyses were used to determine the associations between patient baseline variables, operative variables, ventilator parameters, and complications. RESULTS: Of 1032 patients, 146 patients (14%) had any complication, whereas only 33 patients (3%) had a pulmonary complication. Median body mass index was 37 kg/m(2). Only age was significantly associated with a higher risk of pulmonary complications (P = .01). Older age, higher estimated blood loss, and longer case length were associated with a higher rate of all-cause complications (P = .0001, P < .0001, and P = .004, respectively). No other covariates were strongly associated with complications. CONCLUSION: The vast majority of obese patients can successfully tolerate robotic gynecological surgery and have overall low complications rates and even lower rates of pulmonary complications. The degree of obesity was not predictive of successful robotic surgery and subsequent complications.
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Doenças dos Genitais Femininos/epidemiologia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Pneumopatias/epidemiologia , Obesidade/epidemiologia , Robótica , Adulto , Idoso , Comorbidade , Feminino , Doenças dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
Objective: This study sought to determine if patients with early stage cervical cancer who possessed intermediate-high risk factors (defined by Peters or Sedlis criteria) and had pathologically negative lymph nodes at the time of surgery had higher rates of low volume metastases (LVM) on retrospective ultrastaging. Methods: This IRB-approved retrospective cohort study collected data via chart review on early stage, surgically-treated node-negative cervical cancer patients who underwent postoperative adjuvant therapy, treated at a single institution from January 2011 through June 2021. Nodal blocks were retrospectively ultrastaged per standard protocol. Descriptive statistics were performed for analysis. Results: Over the 10-year study period, n = 20 patients met study inclusion criteria. Most patients were white with squamous cell histology, with a mean number of 25.15 (SD = 12) nodes examined on initial pathologic evaluation. 85 % (n = 17) patients were pathologic stage IB. 85 % of the cohort were recommended for adjuvant radiation, with the remaining 15 % for cisplatin-based chemoradiation. LVM in the form of micrometastasis was retrospectively identified in one patient (5 %) who had received whole pelvic radiation and recurred locally within the irradiated field. Conclusions: This small retrospective series of surgically managed cervical cancer with intermediate-high risk tumor factors identified only 1 patient with LVM, representing 5% of the total population. The biologic importance of ITC and LVM remains unclear in cervical cancer, however this investigation highlights the low incidence even when all nodes are evaluated in a higher risk cohort. The presence of LVM would not have changed management decisions based on this retrospective analysis.
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â¢Metastatic disease to the small bowel may present with intussusception.â¢Clinical decision making for malignant bowel obstruction is difficult and individual specific.â¢Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.
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Introduction: Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in the repair of DNA single-strand breaks (SSB). The recent development of poly(ADP-ribose) polymerase inhibitors (PARPi) results from over 45 years of studies. When the activity of PARP1 or PARP2 is compromised, DNA SSB lesions are unresolved and can be converted to DNA double-strand breaks (DSBs) by the cellular transcription mechanisms. ARID1A (also called BAF250a) is an important component of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex. ARID1A gene demonstrates >50% of mutation rate in ovarian clear-cell carcinomas (OCCC). Mutated or downregulated ARID1A significantly compromises the Homologous Recombination Repair (HRR) of DNA DSB. Results: The present study demonstrated that downregulated or mutated ARID1A attenuates DNA HRR through stimulation of the PI3K/Akt1 pathway and makes tumor cells highly sensitive to PARPi and PARPi/ionizing radiation (IR) combination. We showed that PI3K/Akt1 pathway plays an important role in the sensitization of cancer cell lines with compromised function of ARID1A to PARPi treatment. Discussion: We believe that using of PARPi monotherapy or in combination with radiation therapy is an appealing strategy for treating ARID1A-mutated cancers, as well as many other types of PI3K/Akt1-driven cancers.
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PURPOSE: Endometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT. METHODS AND MATERIALS: Enrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function. RESULTS: Forty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (pâ¯=â¯0.02) while RT without dilation showed a significant decrease (pâ¯=â¯0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (pâ¯=â¯0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (pâ¯=â¯0.14). CONCLUSION: This data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.
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Braquiterapia , Neoplasias do Endométrio , Feminino , Humanos , Vagina/patologia , Braquiterapia/métodos , Estudos Prospectivos , Constrição Patológica/etiologia , Constrição Patológica/patologia , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologiaRESUMO
This case report describes a unique pattern of human epidermal growth factor receptor 2 expression in a patient with uterine carcinosarcoma. The endometrial tumor showed biphasic morphology composed of serous carcinoma and a heterologous high-grade sarcoma component. Human epidermal growth factor receptor 2 immunostaining showed positive (3+) expression in foci of myoinvasion, lymphovascular invasion, and lymph node metastasis but was negative in both the endometrial surface tumor and sarcomatous component. Fluorescent in situ hybridization testing for human epidermal growth factor receptor 2 confirmed no amplification within the endometrial surface carcinoma component and amplification of the lymphovascular invasion component. As the use of human epidermal growth factor receptor 2 immunohistochemical evaluation becomes more commonplace for therapeutic consideration in patients with uterine carcinosarcoma, interpretation of the immunohistochemical should be performed preferentially on large tissue sections including both a surface, myoinvasive portions, and suspected areas of lymphovascular invasion and lymph node metastasis.
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PURPOSE: GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS: Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS: Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time (P < .001) for all three groups. A group by time interaction (P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION: Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.
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Neoplasias Ovarianas , Qualidade de Vida , Idoso , Carcinoma Epitelial do Ovário , Fadiga , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Cuidados Paliativos , Avaliação de SintomasRESUMO
BACKGROUND: Lipomatous tumors of the vulva are exceedingly rare, particularly in adolescents. We describe the work-up and management of an adolescent girl who presented with a large, well-vascularized vulvar mass. CASE: A 14-year-old girl presented with a large vulvar mass of unclear etiology. Magnetic resonance imaging of this mass revealed an ill-defined, well-vascularized mass with fat signal characteristics suggestive of a lipomatous tumor that was concerning for malignancy. We performed complete resection of the mass, and histologic evaluation revealed a vulvar hibernoma. There have been no signs of recurrence 1 year later. SUMMARY AND CONCLUSION: Although rare, a hibernoma of the vulvar region may present in adolescence and may be concerning for malignancy on imaging. Complete resection of these tumors is recommended for definitive diagnosis and treatment.