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OBJECTIVES: The aim of this prospective study was to compare perioperative opioid use in women by status of CYP2D6, a highly polymorphic pharmacogene relevant to opioid metabolism. METHODS: Patients undergoing laparotomy were prospectively recruited and provided a preoperative saliva swab for a pharmacogenomic (PGx) gene panel. Postoperative opioid usage and pain scores were evaluated via chart review and a phone survey. Pharmacogenes known to be relevant to opioid metabolism were genotyped, and opioid metabolizing activity predicted by CYP2D6 genotyping. Patient and procedural factors were compared using Fisher's exact and Kruskal-Wallis tests. RESULTS: The 96 enrolled patients were classified as ultra-rapid (N = 3, 3%), normal (58, 60%), intermediate (27, 28%), and poor (8, 8%) opioid metabolizers. There was no difference in surgical complexity across CYP2D6 categories (p = 0.61). Morphine Milligram Equivalents (MME) consumed during the first 24 h after peri-operative suite exit were significantly different between groups: ultrarapid metabolizers had the highest median MME (75, IQR 45-88) compared to the other three groups (normal metabolizers 23 [8-45], intermediate metabolizers 48 [20-63], poor metabolizers 31 [12-53], p = 0.03). Opioid requirements were clinically greater in ultrarapid metabolizers during the second 24 h and last 24 h but were statistically similar (p = 0.07). There was no difference in MME prescribed at discharge (p = 0.22) or patient satisfaction with pain control (p = 0.64) between groups. CONCLUSIONS: A positive association existed between increased CYP2D6 activity and in-hospital opioid requirements, especially in the first 24 h after surgery. This provides important information to further individualize opioid prescriptions for patients undergoing laparotomy for gynecologic pathology.
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Analgésicos Opioides , Citocromo P-450 CYP2D6 , Laparotomia , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/genética , Dor Pós-Operatória/etiologia , Feminino , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Pessoa de Meia-Idade , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Estudos Prospectivos , Laparotomia/efeitos adversos , Adulto , Idoso , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/genética , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Farmacogenética , GenótipoRESUMO
OBJECTIVE: To assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery. METHODS: Endometrial cancer patients with lymph node micrometastasis or macrometastasis (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIC) after surgical staging at five referral centers worldwide from October 2013 to September 2022 who underwent molecular classification were identified. Endometrial cancers were categorized into four molecular classes: POLE mutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile. Survival analyses using Kaplan-Meier and Cox models (univariate and multivariate) were conducted to evaluate the relationship between molecular class and 5-year recurrence free survival. RESULTS: 131 patients were included: 55 (42.0%) no specific molecular profile, 46 (35.1%) mismatch repair deficient, 1 (0.8%) POLE mutated, and 29 (22.1%) p53 abnormal. During a 5 year follow-up period, 50 (38.2%) patients experienced a recurrence with a median time of 1.2 years (interquartile range (IQR) 0.5-1.8). Median follow-up for the remaining 81 patients was 3.1 years (IQR 1.3-4.5). Survival analysis revealed a significant difference in recurrence-free survival between no specific molecular profile, mismatch repair deficient, and p53 abnormal classes (log rank p<0.01). In a model adjusted for type of lymph node metastasis and tumor grade, the molecular class did not retain significance (p=0.13), while in a model adjusted for type of lymph node metastasis and adjuvant therapy, the molecular class retained significance (p<0.01). CONCLUSION: Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.
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OBJECTIVES: Transvaginal ultrasound is typically the initial diagnostic approach in patients with postmenopausal bleeding for detecting endometrial atypical hyperplasia/cancer. Although transvaginal ultrasound demonstrates notable sensitivity, its specificity remains limited. The objective of this study was to enhance the diagnostic accuracy of transvaginal ultrasound through the integration of artificial intelligence. By using transvaginal ultrasound images, we aimed to develop an artificial intelligence based automated segmentation model and an artificial intelligence based classifier model. METHODS: Patients with postmenopausal bleeding undergoing transvaginal ultrasound and endometrial sampling at Mayo Clinic between 2016 and 2021 were retrospectively included. Manual segmentation of images was performed by four physicians (readers). Patients were classified into cohort A (atypical hyperplasia/cancer) and cohort B (benign) based on the pathologic report of endometrial sampling. A fully automated segmentation model was developed, and the performance of the model in correctly identifying the endometrium was compared with physician made segmentation using similarity metrics. To develop the classifier model, radiomic features were calculated from the manually segmented regions-of-interest. These features were used to train a wide range of machine learning based classifiers. The top performing machine learning classifier was evaluated using a threefold approach, and diagnostic accuracy was assessed through the F1 score and area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 302 patients were included. Automated segmentation-reader agreement was 0.79±0.21 using the Dice coefficient. For the classification task, 92 radiomic features related to pixel texture/shape/intensity were found to be significantly different between cohort A and B. The threefold evaluation of the top performing classifier model showed an AUC-ROC of 0.90 (range 0.88-0.92) on the validation set and 0.88 (range 0.86-0.91) on the hold-out test set. Sensitivity and specificity were 0.87 (range 0.77-0.94) and 0.86 (range 0.81-0.94), respectively. CONCLUSIONS: We trained an artificial intelligence based algorithm to differentiate endometrial atypical hyperplasia/cancer from benign conditions on transvaginal ultrasound images in a population of patients with postmenopausal bleeding.
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OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma. METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival. RESULTS: There were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40-0.86; HR 0.65, 95% CI 0.49-0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35-0.79; HR 0.49, 95% CI 0.35-0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37-0.81). CONCLUSIONS: Adjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma.
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Braquiterapia , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Neoplasias Uterinas , Humanos , Feminino , Estudos Retrospectivos , Quimioterapia Adjuvante , Histerectomia , Estadiamento de Neoplasias , Cistadenocarcinoma Seroso/patologia , Neoplasias Uterinas/patologia , Radioterapia Adjuvante , Neoplasias do Endométrio/patologiaRESUMO
OBJECTIVE: To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). METHODS: We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. RESULTS: Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.
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Braquiterapia , Carcinoma Endometrioide , Neoplasias do Endométrio , Feminino , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Braquiterapia/efeitos adversos , Recidiva Local de Neoplasia/patologia , Radioterapia AdjuvanteRESUMO
OBJECTIVES: Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States. METHODS: The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis. RESULTS: Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis. CONCLUSIONS: Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.
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COVID-19 , Neoplasias dos Genitais Femininos , Humanos , Feminino , Estados Unidos/epidemiologia , COVID-19/terapia , Neoplasias dos Genitais Femininos/terapia , Teste para COVID-19 , Hospitalização , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. OBJECTIVE: We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. STUDY DESIGN: Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. RESULTS: Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change, -61.9 post-risk-reducing salpingo-oophorectomy vs +15.2 in controls; P=.02), but no significant differences were seen for the other hormones. CONCLUSION: Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.
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Neoplasias Ovarianas , Salpingo-Ooforectomia , Estradiol , Feminino , Hormônios Esteroides Gonadais , Humanos , Neoplasias Ovarianas/prevenção & controle , Pós-Menopausa , Estudos ProspectivosRESUMO
STUDY OBJECTIVE: To gather validity evidence for and determine acceptability of Surgical Science-Simbionix Hysterectomy Modules for the DaVinci Xi console simulation system (software; 3D Systems by Simbionix [now Surgical Science-Simbionix], Littleton, CO, and hardware; Intuitive Surgical, Inc., Sunnyvale, CA) and evaluate performance benchmarks between novice and experienced or expert surgeons. DESIGN: Prospective education study (Messick validity framework). SETTING: Multicenter, academic medical institutions. PARTICIPANTS: Residents, fellows, and faculty in obstetrics and gynecology were invited to participate at 3 institutions. Participants were categorized by experience level: fewer than 10 hysterectomies (novice), 10 to 50 hysterectomies (experienced), and more than 50 hysterectomies (expert). A total of 10 novice, 10 experienced, and 14 expert surgeons were included. INTERVENTIONS: Participants completed 4 simulator modules (ureter identification, bladder flap development, colpotomy, complete hysterectomy) and a qualitative survey. Simulator recordings were reviewed in duplicate by educators in minimally invasive gynecologic surgery using the Modified Global Evaluative Assessment of Robotic Skills (GEARS) rating scale. MEASUREMENTS AND MAIN RESULTS: Most participants felt that the simulator realistically simulated robotic hysterectomy (64.7%) and that feedback provided by the simulator was as or more helpful than feedback from previous simulators (88.2%) but less helpful than feedback provided in the operating room (73.5%). Participants felt that this simulator would be helpful for teaching junior residents. Simulator-generated metrics correlated with GEARS performance for the bladder flap and ureter identification modules in multiple domains including total movements and total time for completion. GEARS performance for the bladder flap module correlated with experience level (novice vs experienced/expert) in the domains of interest and total score but did not consistently correlate for the other procedural modules. Performance benchmarks were evaluated for the bladder flap module for each GEARS domain and total score. CONCLUSION: The modules were well received by participants of all experience levels. Individual simulation modules appear to better discriminate between novice and experienced/expert users than overall simulator performance. Based on these data and participant feedback, the use of individual modules in early residency education may be helpful for providing feedback and may ultimately serve as 1 component of determining readiness to perform robotic hysterectomy.
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Procedimentos Cirúrgicos Robóticos , Robótica , Competência Clínica , Simulação por Computador , Feminino , Humanos , Histerectomia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/educaçãoRESUMO
As interventional oncology services within radiology mature, image-guided ablation techniques are increasingly applied to recurrent gynecologic malignancies. Ablation may be performed using thermal techniques like cryoablation, microwave ablation, or radiofrequency ablation, as well as non-thermal ones, such as focused ultrasound or irreversible electroporation. Feasibility and approach depend on tumor type, size, number, anatomic location, proximity of critical structures, and goals of therapy. Current indications include local control of limited metastatic disease or palliation of painful bone metastases refractory or unsuitable to conventional therapies. Technical aspects of these procedures, including methods to protect nearby critical structures are presented through illustrative examples. Cases amenable to image-guided ablation include, but are not limited to, hepatic or pulmonary metastases, musculoskeletal metastases, retroperitoneal nodal metastases, pelvic side wall disease, abdominal wall disease, and vaginal or vulvar tumors. Protective maneuvers, such as hydro-displacement of bowel, neuromonitoring, and retrograde pyeloperfusion through ureteral stents, permit safe ablation despite close proximity to vulnerable nerves or organs. Image-guided ablation offers an alternative modality to achieve local tumor control without the risks associated with surgery or systemic treatment in appropriately selected patients. A multidisciplinary approach to use of image-guided ablation includes collaboration between gynecologic oncology, interventional radiology, anesthesia, urology and radiation oncology teams allowing for appropriate patient-centered case selection. Long-term follow up and additional studies are needed to determine the oncologic benefits of such techniques.
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Técnicas de Ablação/métodos , Neoplasias dos Genitais Femininos/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Feminino , HumanosRESUMO
STUDY OBJECTIVE: The objectives of this study were to (1) pilot a robotic console configuration methodology to optimize ergonomic posture, and (2) determine the effect of this intervention on surgeon posture and musculoskeletal discomfort. DESIGN: This was an institutional review board-approved prospective cohort study conducted from February 2017 to October 2017. SETTING: A single tertiary care midwestern academic medical center. PARTICIPANTS: Six fellowship-trained gynecologic surgeons, proficient in robotic hysterectomy, were recruited: 3 men and 3 women. INTERVENTIONS: Each surgeon performed 3 robotic hysterectomies using their self-selected robotic console settings (preintervention). Then, a robotic console ergonomic intervention protocol was implemented by trained ergonomists to improve posture and decrease time in poor ergonomic positions. Each surgeon then performed 3 robotic hysterectomies using the ergonomic intervention settings (postintervention). All surgeries used the da Vinci Xi surgical system (Intuitive Surgical, Inc., Sunnyvale, CA) and were the first case of the day. The surgeons wore inertial measurement unit (IMU) sensors on their head, chest, and bilateral upper arms during surgery. The IMU sensors are equipped with accelerometers, gyroscopes, and magnetometers to give objective measurements of body posture. IMU data were then analyzed to determine the percentage of time spent in ergonomically risky postures as categorized using a modified rapid upper limb assessment. Before and after each hysterectomy, the surgeons completed identical questionnaires for an assessment of musculoskeletal pain/discomfort. The outcome measurements were compared pre- versus postintervention on the basis of fitting generalized linear mixed models that handled the individual surgeon as a random effect and "setting" as a fixed effect. MEASUREMENTS AND MAIN RESULTS: With regard to the IMU posture results, there was a significant decrease in time spent in the moderate- to high-risk neck position and a decrease in average neck angle after the ergonomic intervention. The average percentage of time spent in moderate- to high-risk categories was significantly lower for the neck (mean, 54.3% vs 21.0%; pâ¯=â¯.008) and right upper arm (mean, 15.5% vs 0.9%; pâ¯=â¯.02) when using the intervention settings compared with the surgeons' settings. Pain score results: There were fewer reported increases in neck (4 [22%] vs 1 [6%]) and right shoulder (4 [22%] vs 2 [11%]) pain or discomfort after completion of robotic hysterectomy postintervention versus preintervention; however, these differences did not attain statistical significance (pâ¯=â¯.12 and pâ¯=â¯.37, respectively). CONCLUSION: An ergonomic robotic console intervention demonstrated effectiveness and improved objective surgeon posture at the console when compared with the surgeons' self-selected settings.
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Doenças Profissionais , Procedimentos Cirúrgicos Robóticos , Ergonomia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVES: To report the impact of implementing standardized guidelines for opioid prescriptions after gynecologic surgery and describe patient perspectives before and after implementation for those undergoing laparotomy for ovarian cancer. METHODS: Patients undergoing gynecologic surgery between October 2017 and May 2018 were prescribed opioids at discharge using tiered guidelines; prescriptions were compared to consecutive historical controls (March 2017-October 2017). A subset of ovarian cancer laparotomy patients were surveyed regarding postoperative opioid consumption and patient experience. RESULTS: A total of 620 women in the tiered guideline cohort were compared with 599 historical controls. Following implementation, 95.8% of prescriptions met guidelines. Median milligram morphine equivalents (MME) prescribed decreased from 150 to 75 (p ≤ 0.001) with no change in opioid refills (7.7 vs 6.9%, p = 0.62). In surveyed ovarian cancer patients, 100% of tiered guideline patients and 92% of historical controls felt satisfied with pain control (p = 0.24), despite a 50% reduction in prescribed MME and 14.6% receiving no opioids at discharge (p = 0.002). The median (IQR) MME consumed after discharge was 15 (0, 75) in tiered guideline patients vs. 24 (0, 135) in historical controls, and 38.2% and 42.4% consumed no opioids, respectively. Mean time between surgery and opioid use cessation was <1 week in both groups; patients' perceptions of opioid prescription appropriateness did not change (p = 0.49). More than 75% of patients kept their remaining opioids rather than dispose of them. CONCLUSIONS: Reducing prescribed opioids after gynecologic surgery using tiered guidelines did not increase opioid refills or worsen patients' perceptions of postoperative pain. Even after laparotomy, very little opioids were required over a short duration after dismissal. Infrequent disposal of leftover opioids highlights the need to avoid over-prescribing.
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Analgésicos Opioides/administração & dosagem , Neoplasias Ovarianas/cirurgia , Manejo da Dor/normas , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Pessoa de Meia-Idade , Manejo da Dor/métodos , Guias de Prática Clínica como Assunto , Prescrições/normas , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To examine the effect of robotic-assisted surgery implementation for treatment of endometrial cancer in the United States on 30-day clinical outcomes and costs. METHODS: We retrospectively reviewed data of adult patients who underwent total hysterectomy for endometrial cancer in the US hospitals in Premier Healthcare Database between January 1, 2008 and September 30, 2015. We conducted trend analyses comparing the proportions of surgical approaches with the associated clinical outcomes and costs over the study period using Mann-Kendall tests. Clinical outcomes and costs of robotic-assisted surgery, laparoscopic and open surgery have been compared after propensity score 1:1 matching in the most recent 3 years (January 1, 2013-September 30, 2015). RESULTS: Of a total of 35,224 patients, use of robotic-assisted surgery increased from 9.48% to 56.82% while open surgery decreased from 70.4% to 28.1% over the study period. A 2.5% decrease in major complications (P < .001), a 2.9% decrease in minor complications (P = .001), and a 2.0% decrease 30-day readmissions (P = .001) was observed across all surgical approaches. Perioperative 30-day total cost slightly decreased from US $11,048 to US $10,322 (P = .08). Among propensity-score matched patients, robotic-assisted surgery was associated with shorter hospitalization than open surgery (median [interquartile range], 2.0 [2.0-3.0] vs 4.0 [3.0-6.0] days) and laparoscopic surgery (2.0 [2.0-3.0] vs 3.0 [2.0-4.0] days), fewer 30-day complications (20.1% vs 33.7%) (all P < .001), and comparable perioperative 30-day total costs (median [interquartile range], US $12,200 [US $9,509-US $16,341] vs US $12,018 [US $8,996-US $17,162]; P = .34) with open surgery. CONCLUSION: Robotic-assisted surgery facilitated the widespread diffusion of a minimally invasive approach nationally for endometrial cancer, with reduction of perioperative morbidity and no increase in overall treatment-related 30-day costs at national level.
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Neoplasias do Endométrio/cirurgia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the relationship between frailty and chemotherapy delivery among women with epithelial ovarian cancer (EOC). METHODS: We included women who underwent primary debulking surgery (PDS) for stage IIIC/IV EOC between 1/2/2003 and 12/30/2011, received adjuvant chemotherapy at our institution, and had data available to calculate a frailty deficit index. Frailty was defined as a frailty deficit index ≥0.15. Relative dose intensity (RDI) of chemotherapy was calculated as the percentage of the standard dose that was administered, and compared between frail and non-frail using the Wilcoxon rank-sum test. RESULTS: Failure to receive chemotherapy following PDS was twice as common among frail vs. non-frail women (26.7% vs 14.2%, p = 0.001). Of the 169 women who received chemotherapy at our institution, 17.2% (29/169) were frail. Frail women were older (mean, 67.9 vs 62.3 years, p = 0.01), had higher BMI (mean, 29.6 vs 25.7 kg/m2, p = 0.003), and were less likely to complete 6 cycles of chemotherapy (75.9 vs. 93.6%, p = 0.008). Using an RDI cutoff of 85%, frail women were less likely to have adequate doses of carboplatin (15.8 vs. 66.2%, p < 0.001) and paclitaxel (57.9 vs. 80.5%, p = 0.07) despite no differences in dose delays (34.5 vs. 42.1%), dose reductions (65.5 vs. 68.6%), and severe neutropenia (44.8 vs. 39.3%). After adjusting for age, frailty was associated with shorter progression-free (HR 1.58, 95% CI: 0.99-2.50) and overall survival (HR 2.14, 95% CI: 1.35-3.41). CONCLUSION: Frail women with EOC were less likely to receive chemotherapy or the optimal dose of chemotherapy after PDS despite no evidence of treatment-related toxicity. Frail EOC patients demonstrated shorter progression-free and overall survival. Further studies are needed to explore the association between frailty, chemotherapy, and survival.
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Antineoplásicos/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Fragilidade/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.
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Adenocarcinoma de Células Claras/cirurgia , Algoritmos , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Adenocarcinoma de Células Claras/patologia , Idoso , Estudos de Coortes , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Resultado do TratamentoRESUMO
BACKGROUND: In the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking. PRIMARY OBJECTIVES: To assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes. STUDY HYPOTHESIS: We hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%). TRIAL DESIGN: This prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with <50% myometrial invasion), negative pelvic peritoneal cytology, and bilateral sentinel lymph nodes negative for malignancy; (iii) recommended adjuvant treatment: vaginal brachytherapy or no adjuvant treatment. PRIMARY ENDPOINT: Incidence of pelvic/non-vaginal recurrence at 36 months. SAMPLE SIZE: 182 patients for study cohort ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual will be completed in 2023 with results reported in 2026. TRIAL REGISTRATION: NCT04291612.
Assuntos
Adenocarcinoma/patologia , Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Feminino , Humanos , Metástase Linfática/patologia , Recidiva Local de Neoplasia/diagnóstico , Estudos ProspectivosRESUMO
OBJECTIVE: The role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant therapy in patients with stage IIIC2 endometrial cancer. METHODS: This retrospective single-institution study assessed patients with stage IIIC2 endometrial cancer who underwent primary surgery from January 1984 to December 2014. All patients had hysterectomy (±salpingo-oophorectomy) plus lymphadenectomy (para-aortic nodes, ±pelvic nodes). We included all patients with stage III endometrial cancer and documented para-aortic lymph node metastases (International Federation of Obstetrics and Gynecologists stage IIIC2). We excluded patients who did not provide consent, who had synchronous cancer, or who underwent neoadjuvant chemotherapy. Follow-up was restricted to the first 5 years post-operatively. Cox proportional hazards models, with age as the time scale, was used to evaluate associations of risk factors with disease-free survival and overall survival. RESULTS: Among 105 patients with documented adjuvant therapy, external beam radiotherapy was administered to 25 patients (24%), chemotherapy to 24 (23%), and a combination (chemotherapy and external beam radiotherapy) to 56 (53%) patients. Most patients receiving chemotherapy and external beam radiotherapy (80%) had chemotherapy first. The majority of relapses had a distant component (31/46, 67%) and only one patient had an isolated para-aortic recurrence. Non-endometrioid subtypes had poorer disease-free survival (HR 2.57; 95% CI 1.38 to 4.78) and poorer overall survival (HR 2.00; 95% CI 1.09 to 3.65) compared with endometrioid. Among patients with endometrioid histology (n=60), chemotherapy and external beam radiotherapy improved disease-free survival (HR 0.22; 95% CI 0.07 to 0.71) and overall survival (HR 0.28; 95% CI 0.09 to 0.89) compared with chemotherapy or external beam radiotherapy alone. Combination therapy did not improve prognosis for patients with non-endometrioid histology (n=45). CONCLUSIONS: In our cohort of patients with stage IIIC2 endometrioid endometrial cancer, those receiving chemotherapy and external beam radiotherapy had improved survival compared with patients receiving chemotherapy or external beam radiotherapy alone. However, the prognosis of patients with non-endometrioid endometrial cancer remained poor, regardless of the adjuvant therapy administered. Distant recurrences were the most common sites of failure.
Assuntos
Carcinoma Endometrioide/secundário , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Idoso , Aorta , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Histerectomia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pelve , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Besides histologic features, the presence of nodal metastasis is the most crucial prognostic factor for recurrence and survival for patients with gynecologic cancer. Conventionally, lymphadenectomy has been performed routinely to assess lymphatic metastasis. However, lymphadenectomy may be unnecessary in early-stage gynecologic cancer, because the percentage of patients with lymph node involvement is very low. The recent use of sentinel lymph node mapping has provided high feasibility, safety, and accuracy in the assessment of nodal metastasis. The National Comprehensive Cancer Network Clinical Practice Guidelines have incorporated the sentinel lymph node for nodal evaluation in vulvar, endometrial, and cervical cancers.
Assuntos
Neoplasias do Endométrio/terapia , Metástase Linfática/terapia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias do Colo do Útero/terapia , Neoplasias Vulvares/terapia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/patologiaRESUMO
OBJECTIVE: To identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC). METHODS: Clinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2â¯mm and >2â¯mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis. RESULTS: Of 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44-73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22-115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33-5.16]). CONCLUSIONS: Presence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC.
Assuntos
Neoplasias do Endométrio/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Idoso , Estudos de Coortes , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Modelos Logísticos , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify predictors of unsuccessful sentinel lymph node (SLN) mapping in patients with apparent early-stage endometrial cancer (EC) undergoing surgical staging with cervical injection of indocyanine green and SLN biopsy. METHODS: We retrospectively identified consecutive patients with EC with attempted SLN biopsy between June 2014 and June 2016 at our institution. Patients were grouped according to whether they had a successful procedure, defined as the bilateral identification of SLNs, or an unsuccessful procedure, defined as unilateral or no SLN mapping. Logistic regression was used to evaluate predictors of an unsuccessful procedure. RESULTS: Among 327 patients included in the analysis, 256 (78.3%) had a successful procedure and 71 (21.7%) had an unsuccessful procedure (15.0% unilateral SLN mapping, 6.7% no mapping). The rate of successful procedure increased from 57.7% to 83.3% between the first and last quarters of the 2-year study period, which represented the learning curve for the technique. The mean (SD) operative time decreased from 164 (55) to 137 (37) minutes. By multivariable analysis, lysis of adhesions at the beginning of surgery (odds ratio, 3.07; 95% CI, 1.56-6.07) and the presence of enlarged lymph nodes (odds ratio, 4.69; 95% CI, 1.82-12.11) were independently associated with an unsuccessful procedure. CONCLUSIONS: Lysis of adhesions at the beginning of surgery and the presence of enlarged lymph nodes independently affect the bilateral detection of SLNs.