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1.
Gynecol Oncol ; 168: 107-113, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36423445

RESUMO

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.


Assuntos
Carcinoma , Neoplasias do Endométrio , Linfadenopatia , Linfonodo Sentinela , Humanos , Feminino , Linfonodo Sentinela/patologia , Excisão de Linfonodo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Linfadenopatia/patologia , Carcinoma/patologia
2.
Int J Gynecol Cancer ; 32(7): 875-881, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35680137

RESUMO

OBJECTIVE: We aimed to evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy. METHODS: We conducted a retrospective study of elderly (>65-year-old) patients diagnosed with endometrial cancer between December 2007 and August 2017. These patients had been treated at a single center in Montreal, Canada. We compared the surgical and oncological outcomes of three cohorts undergoing surgical staging in non-overlapping eras: 1) lymphadenectomy, 2) lymphadenectomy and SLN sampling, 3) SLN sampling alone. Using life tables, Kaplan-Meier survival curves and log-rank tests, we analyzed 2-year progression-free survival, overall survival, and disease-specific survival. RESULTS: Our study included 278 patients with a median age of 73 years (range; 65-91): 84 (30.2%) underwent lymphadenectomy, 120 (43.2%) underwent SLN sampling with lymphadenectomy, and 74 (26.6%) had SLN sampling alone. The SLN sampling alone group had shorter operative times with a median duration of 199 minutes (range, 75-393) compared with 231 (range, 125-403) and 229 (range, 151-440) minutes in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts; respectively (p<0.001). The SLN sampling alone group also had lower estimated blood loss with a median loss of 20 mL (range, 5-150) vs 25 mL (range, 5-800) and 40 mL (range, 5-400) in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts, respectively (p=0.002). The 2 year overall survival and progression-free survival were not significantly different between the three groups (p=0.45, p=0.51, respectively). On multivariable analysis after adjusting for age, American Society of Anesthesiologists (ASA) score, stage, grade, and lymphovascular space invasion, adding SLN sampling was associated with better overall survival, (HR 0.2, CI [0.1 to 0.6], p=0.006) and progression-free survival (HR 0.5, CI [0.1 to 1.0], p=0.05). CONCLUSION: Sentinel lymph node-based surgical staging is feasible and associated with better surgical outcomes and comparable oncological outcomes in elderly patients with intermediate and high-risk endometrial cancer.


Assuntos
Neoplasias do Endométrio , Linfadenopatia , Linfonodo Sentinela , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfadenopatia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
3.
Gynecol Oncol ; 162(2): 256-261, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119364

RESUMO

OBJECTIVE: To evaluate if the prognostic value of lymphovascular space invasion (LVSI) is different in endometrial cancer patients with negative lymph nodes following sentinel lymph node (SLN) mapping or lymph node dissection (LND) as staging procedure. MATERIAL AND METHODS: A retrospective study of 510 patients diagnosed with endometrial carcinoma in our institution between 2007 and 2014. We excluded patients that were diagnosed with positive nodes (Stage IIIc). We compared patients' characteristics and survival outcomes as function of their LVSI status (positive LVSI vs negative LVSI subgroups) in each cohort separately. RESULTS: 413 patients met the inclusion criteria, out of whom 239 underwent SLN and 174 patients underwent LND only. In the SLN group, life table analysis showed 5-year OS and PFS of 80% and 72% in patients with LVSI compared to 96%, and 93% without LVSI. Same trend was observed among patients with LND with 5-year OS and PFS of 74% and 64% in patients with LVSI compared to 97%, and 90% without LVSI. On multivariable analysis, adjusted for age, FIGO stage, grade and maximal tumor size, the favorable survival of negative LVSI remained only in the LND cohort (SLN cohort: HR 1.2, CI [0.3-4.0], P = 0.8 and HR 1.7, CI [0.7-4.3], p = 0.2 for OS and PFS, respectively; LND cohort: HR 3.1, CI [1.4-6.5], p < 0.001 and HR 2.5, CI [1.2-4.9], p = 0.01 for OS and PFS, respectively). CONCLUSIONS: The prognostic value of LVSI disappears when patients undergo staging with SLN and are found to have negative nodes in contrast to those who have undergone LND. Future studies should confirm our observation on patients with negative sentinel nodes, and plan on tailoring adjuvant treatment to this specific subgroup.


Assuntos
Vasos Sanguíneos/patologia , Neoplasias do Endométrio/mortalidade , Vasos Linfáticos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Histerectomia , Excisão de Linfonodo , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Salpingo-Ooforectomia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos
4.
J Minim Invasive Gynecol ; 28(8): 1446, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33387689

RESUMO

STUDY OBJECTIVE: Surgical staging for apparent early-stage ovarian cancer includes systematic pelvic and para-aortic lymph node evaluation to detect occult stage III disease [1]. Although, lymphadenectomy procedure is associated with increased duration of surgery and a 13% risk of lymphocyst formation [2]. Sentinel lymph node (SLN) biopsy is still investigational, and no standardized approach has been studied. Recent mounting evidence has approved the applicability of SLN technique in early-stage ovarian cancer [3,4]. The objective of this video is to demonstrate a surgical technique for robotic performance of SLN biopsy in presumed early-stage ovarian cancer. DESIGN: Stepwise demonstration of the robotic technique for SLN sampling in presumed early-stage ovarian cancer. This video report is part of an institutional, investigational review board-approved study. SETTING: Academic tertiary referral center. INTERVENTIONS: This video presents our team's robotic technique for SLN sampling in a 37-year-old woman who presented to our center with a 10-cm right complex adnexal mass, suspicious for malignancy. A 27-gauge spinal needle was inserted through the abdominal wall under direct visualization. We injected 0.5 mL of dilute indocyanine green solution (Novadaq Technologies, Mississauga, Ontario, Canada) (1.25 mg/mL) subperitoneally into the utero-ovarian ligament. The SLN was checked with the fluorescence-guided camera of the Xi DaVinci robotic system (Sunnyvale, CA). Eight to 10 minutes after the injection, a right para-aortic SLN was identified, and dissection was performed. After dissection, the node was extracted and sent to pathology for evaluation by ultra-staging. The final pathology revealed a stage IA low-grade serous ovarian cancer. CONCLUSION: SLN sampling appears to be feasible in presumed early-stage ovarian cancer and may allow the avoidance of systematic lymph node dissection in this set of patients.


Assuntos
Neoplasias do Endométrio , Neoplasias Ovarianas , Linfonodo Sentinela , Adulto , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Verde de Indocianina , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Ontário , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela
5.
J Minim Invasive Gynecol ; 28(5): 947-956, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33249269

RESUMO

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial cancer (EC) in BRCA1 or BRCA2 germline mutation carriers and to examine the justifiability of prophylactic hysterectomy at the time of RRSO. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched. Eleven articles were selected and analyzed using the OpenMetaAnalyst 2012 software. METHODS OF STUDY SELECTION: Randomized controlled studies, cohort studies, and case-control studies evaluating the risk of EC and specifically uterine papillary serous carcinoma (UPSC) in germline BRCA1/2 mutation carriers were included. Articles were excluded if they did not meet the inclusion criteria, or if data were not reported and the authors did not respond to inquiries. We assessed the methodological quality of the included studies on the basis of the Newcastle-Ottawa scale. Dichotomous results from each of the studies eligible for the meta-analysis were expressed as the proportion of patients with EC or UPSC per total number of BRCA mutation carriers, with 95% confidence interval (CI). The Mantel-Haenszel statistical method was used. TABULATION, INTEGRATION, AND RESULTS: Eleven studies reported the outcome of interest and were included in the final meta-analysis. In total, 13 871 carriers of BRCA1 and BRCA2 mutations were identified. The pooled prevalence rates of EC and UPSC in BRCA1/2 mutation carriers were 82/13 827 (0.59%) and 19/11 582 (0.16%), respectively. The EC prevalence was 46/7429 (0.62%) in BRCA1 mutation carriers and 17/3546 (0.47%) in BRCA2 mutation carriers, with relative risk of 1.18 (95% CI, 0.7-2.0). For UPSC, the prevalence was 15/7429 (0.2%) and 3/3546 (0.08%) among BRCA1 and BRCA2 mutation carriers, respectively, (relative risk 1.39; 95% CI, 0.5-3.7). CONCLUSION: Most studies in this meta-analysis suggest a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The decision regarding concurrent hysterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.


Assuntos
Neoplasias da Mama , Neoplasias do Endométrio , Neoplasias Ovarianas , Proteína BRCA2/genética , Neoplasias do Endométrio/genética , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Células Germinativas , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Mutação , Neoplasias Ovarianas/genética , Ovariectomia
6.
J Minim Invasive Gynecol ; 28(5): 957-970, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33279627

RESUMO

OBJECTIVE: To review short- and long-term complications associated with intraoperative rupture of benign ovarian cysts. DATA SOURCES: The Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched using the following terms and their combinations: "spillage," "rupture," "leakage," "ovarian cyst," "teratoma," "dermoid," "operative," "surgery," "outcome." METHODS OF STUDY SELECTION: Randomized controlled and observational studies evaluating the operative outcomes of surgical treatment of ovarian cysts with intraoperative spillage compared with those of surgical treatment of ovarian cysts without spillage were included. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. TABULATION, INTEGRATION, AND RESULTS: A total of 28 studies were included in the qualitative analysis and 12 in the quantitative analysis. Ovarian cyst diameter was not found to be associated with the risk for spillage (relative risk [RR] 0.75; 95% confidence interval [CI], -0.33 to 1.82). Intraoperative benign ovarian cyst rupture was not associated with adverse short- and long-term outcomes such as reoperation (RR 1.16; 95% CI, 0.39-3.48), infertility (RR 0.73; 95% CI, 0.15-3.63), transient fever (RR 3.22; 95% CI, 0.83-12.51), and readmission (RR 1.00; 95% CI, 0.33-2.98). However, intraoperative spillage was found to be associated with increased risk for benign recurrence (RR 3.1; 95% CI, 1.05-9.14). A subgroup analysis of the studies that included only dermoid cysts showed an association between intraoperative cyst rupture and postoperative chemical peritonitis (RR 9.36; 95% CI, 1.20-73.28). CONCLUSION: Intraoperative ovarian cyst spillage of a benign cyst is associated with limited adverse clinical outcomes. Although the surgical approach (minimally invasive vs open) should not be affected by the concern regarding an intraoperative cyst rupture, maximal efforts should be made to prevent intra-abdominal spillage.


Assuntos
Laparoscopia , Cistos Ovarianos , Peritonite , Teratoma , Feminino , Humanos , Recidiva Local de Neoplasia , Cistos Ovarianos/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Teratoma/cirurgia
7.
J Obstet Gynaecol Can ; 43(10): 1136-1144.e1, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33984524

RESUMO

OBJECTIVE: Although its use in endometrial cancer staging is relatively new, sentinel lymph node (SLN) sampling has been shown to be highly accurate and is associated with few complications. However, some studies report lower rates of detection with SLN sampling among patients with obesity. The aim of the current study is to evaluate the feasibility of SLN sampling in endometrial cancer for patients with obesity, and to determine whether omitting lymph node dissection (LND) in surgical staging using SLN sampling impacts oncologic outcomes. METHODS: we conducted a retrospective study of patients with obesity (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, that compared surgical and oncologic outcomes of 2 cohorts: patients who underwent LND and patients who underwent SLN without lymphadenectomy. The primary outcome was operative time. Secondary outcomes included intraoperative bleeding; lymph node assessment information; intraoperative and postoperative adverse events; and oncologic outcomes including progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS). PFS was defined as the time from surgery to the recurrence or death from any cause. OS was defined as time from diagnosis to death or the last date the patient was known to be alive, and DSS was defined as the time from the surgery to death from the disease. RESULTS: Out of 223 patients with a median BMI of 40.6 kg/m2, 140 underwent LND and 83 underwent SLN alone. The median operative time for patients in the SLN group was shorter than that of patients in the LND group (190.5 [range 108-393] vs. 238 [131-440] min; P < 0.001), and the SLN group had lower median estimated blood loss than the LND group (30 [range 0-300] vs. 40 [range 0-800] mL; P = 0.03). At the 24-month follow-up cut-off, 98% of patients were alive and 95.5% were disease free, with no significant differences in OS, DSS, and PFS between the 2 groups (P = 0.7, P = 0.8, and P = 0.4, respectively). CONCLUSIONS: In patients with obesity, omitting LND from surgical staging with SLN sampling was associated with shorter operative times and less bleeding and did not affect survival at 2 years.


Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Obesidade/complicações , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela
8.
Gynecol Oncol ; 158(1): 84-91, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32349874

RESUMO

OBJECTIVE: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). METHODS: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. RESULTS: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). CONCLUSION: Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.


Assuntos
Neoplasias do Endométrio/patologia , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodo Sentinela/cirurgia
9.
J Surg Oncol ; 122(2): 306-314, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32291783

RESUMO

OBJECTIVE: To evaluate the impact of surgical wait times on outcome of patients with grade 3 endometrial cancer. METHODS: All consecutive patients surgically treated for grade 3 endometrial cancer between 2007 and 2015 were included. Patients were divided into two groups based on the time interval between endometrial biopsy and surgery: wait time from biopsy to surgery ≤12 weeks (84 days) vs more than 12 weeks. Survival analyses were conducted using log-rank tests and Cox proportional hazards models. RESULTS: A total of 136 patients with grade 3 endometrial cancer were followed for a median of 5.6 years. Fifty-one women (37.5%) waited more than 12 weeks for surgery. Prolonged surgical wait times were not associated with advanced stage at surgery, positive lymph nodes, increased lymphovascular space invasion, and tumor size (P = .8, P = 1.0, P = .2, P = .9, respectively). In multivariable analysis adjusted for clinical and pathological factors, wait times did not significantly affect disease-specific survival (adjusted hazard ratio [HR]: 1.2, 95% confidence interval [CI], 0.6-2.5, P = .6), overall survival (HR: 1.1, 95% CI, 0.6-2.1, P = .7), or progression-free survival (HR: 0.9, 95% CI, 0.5-1.7, P = .8). CONCLUSION: Prolonged surgical wait time for poorly differentiated endometrial cancer seemed to have a limited impact on clinical outcomes compared to biological factors.


Assuntos
Neoplasias do Endométrio/cirurgia , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Canadá , Estudos de Coortes , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
10.
Acta Obstet Gynecol Scand ; 99(7): 933-940, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31954071

RESUMO

INTRODUCTION: The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome. MATERIAL AND METHODS: This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population. RESULTS: In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05). CONCLUSIONS: Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer.


Assuntos
Antígeno Ca-125/metabolismo , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Quebeque , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Obstet Gynaecol Can ; 42(11): 1339-1345, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32859533

RESUMO

OBJECTIVE: To perform a hypothesis-generating evaluation of patient outcomes following neoadjuvant chemotherapy (NACT) compared with those following primary debulking surgery (PDS) in patients over age 75 with high-grade ovarian cancer. METHODS: This was a retrospective cohort study of consecutive patients aged 75 years and older, with high-grade ovarian cancer. Data were analyzed in SPSS 25.0 using descriptive statistics to characterize groups based on primary treatment modality, Kaplan-Meier survival curves to estimate overall and progression-free survival, and Cox proportional hazards to analyze confounders. RESULTS: Of 429 patients with stages III and IV high-grade ovarian cancer (endometrioid and serous), 71 were aged older than 75 years and met our criteria for inclusion; 58 were treated with NACT while 13 underwent primary debulking. Sixteen patients did not undergo interval debulking following NACT. There were no significant differences in demographic characteristics between the groups. Following NACT, more patients were completely debulked-36.2% versus 21% (P = 0.000)-and had a shorter length of stay (5 vs. 7 d; P = 0.018). Overall survival was similar between the NACT and PDS groups (58.7 vs. 59.7 mo; LR -0.836; P = 0.361) despite lower progression-free survival in the NACT group (25.9 vs. 47.1 mo; P = 0.042; LR 4.31). Both progression-free and overall survival were significantly higher when patients undergoing NACT achieved complete debulking (21.7 and 102.3 mo, respectively) compared with suboptimal debulking (12.03 and 14.2 mo, respectively). CONCLUSION: In this select group older patients with stage III and IV high-grade ovarian cancers, neoadjuvant chemotherapy may be considered without compromising outcomes and contributes to complete debulking.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/mortalidade , Feminino , Humanos , Proteínas de Membrana/sangue , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
BMC Cancer ; 19(1): 44, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630446

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become the first targeted therapies available in the treatment of patients with high-grade serous ovarian cancer (HGSOC). We recently described a significant reduction in PARP1 protein levels in vitro and in vivo in patients treated with standard carboplatinum-paclitaxel chemotherapy, raising the question whether the sequence of treatment used today with chemotherapy followed by PARPi is optimal. In this study, we aim to evaluate if the sequence of PARPi followed by chemotherapy could be more beneficial. METHODS: BRCA1-mutated (UWB1.287, SNU-251), epigenetically-silenced (OVCAR8), and wild-type (SKOV3, A2780PAR & A2780CR) ovarian cancer cell lines were exposed to clinically relevant doses of PARPi followed by different doses of standard chemotherapy and compared to the inverse treatment. The therapeutic efficacy was assessed using colony formation assays. Flow cytometry was used to evaluate cell apoptosis rate and the changes in cell cycle. Finally, apoptotic and cell cycle protein expression was immunodetected using western blot. RESULTS: Exposure to PARPi prior to standard chemotherapy sensitized BRCA1-mutated or epigenetically-silenced BRCA1 cell lines to lower doses of chemotherapy. Similar results were observed in BRCA1 wild-type and cell lines in which BRCA1 functionality was restored. Moreover, this treatment increased the apoptotic rate in these cell lines. CONCLUSION: Pre-treatment with PARPi followed by standard chemotherapy in vitro is more efficient in growth inhibition and induction of apoptosis compared to the administration of standard chemotherapy followed by PARPi.


Assuntos
Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína BRCA1/antagonistas & inibidores , Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Cisplatino/farmacologia , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Terapia de Alvo Molecular , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Reparo de DNA por Recombinação
13.
Gynecol Oncol ; 155(1): 27-33, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31349997

RESUMO

OBJECTIVE: To assess risk factors for lymph node involvement in patients with endometrial cancer and a body-mass index (BMI) ≥30 kg/m2. MATERIALS AND METHODS: A retrospective analysis was performed of obese patients diagnosed with endometrial carcinoma between 2007 and 2015, treated in a single center in Montreal. Preoperative variables evaluated were age, BMI, parity, and preoperative ASA score, grade, CA-125 and histology. Odds ratios (OR) and hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were calculated using multivariable logistic regression and Cox proportional hazard models. RESULTS: The study included 230 women with BMI ≥30, 223 (97.0%) had complete staging. Pelvic lymph node involvement was detected in 26 patients (11.3%). Sentinel node detection and pelvic lymph node dissection decreased with increasing BMI (adjusted OR 0.86, 95%CI 0.76-0.97 and 0.76, 95%CI 0.59-0.96, respectively, per 1 kg/m2 increment). Pelvic lymph node involvement was inversely correlated with BMI (adjusted OR 0.88, 95%CI 0.79-0.99) and present in 16/85 (18.8%), 6/56 (10.7%), and 4/82 (4.9%) of patients with a BMI of 30.0-34.9, 35.0-39.9, and ≥40.0 kg/m2, respectively. Preoperative CA-125 was associated with lymph node involvement (adjusted OR 2.77, 95%CI 1.62-4.73, per quartile increment). CONCLUSION: Pelvic lymph node dissection might be omitted in selected cases of morbidly obese patients with failed sentinel nodes mapping and a low CA-125.


Assuntos
Neoplasias do Endométrio/patologia , Linfonodos/patologia , Obesidade Mórbida/patologia , Idoso , Índice de Massa Corporal , Antígeno Ca-125/metabolismo , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/metabolismo , Linfonodos/cirurgia , Metástase Linfática , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Estudos Retrospectivos , Fatores de Risco
14.
Int J Gynecol Cancer ; 29(7): 1121-1125, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31320490

RESUMO

OBJECTIVE: Sentinel lymph node (SLN) mapping is increasingly being used in the treatment of apparent early-stage endometrial cancer. The aim of this study was to evaluate whether three tracers (blue dye, indocyanine green (ICG), and technetium-99 (Tc99)) performed better than two (ICG and Tc99). STUDY DESIGN: Prospective study of all consecutive patients (n=163) diagnosed with clinical early-stage endometrial cancer from 2015 to 2017. All patients were randomly assigned to receive a mixture of ICG and Tc99 with or without blue dye. Subgroup analysis for detection rates was performed for each group (double versus triple tracer). RESULTS: One hundred and fifty-seven patients met the inclusion criteria. Eighty patients received ICG and Tc99 with unilateral and bilateral SLN detection rates of 97.5% and 81.3%, respectively. Seventy-seven patients received all three tracers with unilateral and bilateral detection rates of 93.5% and 80.5%, respectively. Only one patient in the triple tracer group was detected by blue dye alone. No significant differences were noticed in unilateral or bilateral detection rates between the two groups, nor in the detection of lymph node metastasis. CONCLUSION: The addition of blue dye to ICG and Tc99 did not demonstrate any improvement in SLN detection.


Assuntos
Corantes , Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Idoso , Feminino , Humanos , Verde de Indocianina , Metástase Linfática , Pessoa de Meia-Idade , Estudos Prospectivos , Corantes de Rosanilina , Tecnécio
15.
Int J Gynecol Cancer ; 29(9): 1341-1347, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601648

RESUMO

INTRODUCTION: With the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III-IV ovarian cancer. METHODS: All patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III-IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III-IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery. RESULTS: A total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24-88), 78% had stage III disease, and the median follow-up time was 37 months (5.6-91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10-1250 mL), and the median hospital stay was 1 day. CONCLUSION: Robotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Idoso , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
16.
J Obstet Gynaecol Can ; 41(4): 450-458, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30529223

RESUMO

OBJECTIVE: In view of the recent controversy concerning the use of minimally invasive radical hysterectomy as primary treatment for early stage cervical cancer, this study compared the survival and perioperative outcomes in a cohort of patients who underwent radical hysterectomy either by laparotomy or by robotics. METHODS: This retrospective study compared all consecutive patients with early stage cervical cancer since the beginning of the Division of Gynecologic Oncology at the Jewish General Hospital in 2003, who underwent robotic radical hysterectomy (n = 74) with a cohort of all consecutive patients from the immediate past who underwent open radical hysterectomy (n = 24) for early stage cervical cancer. All patients were treated at the Jewish General Hospital in Montréal (Canadian Task Force Classification II-2). RESULTS: The median follow-up time for the robotic group was 46 months. During that time, 7% and 17% of patients in the robotic group and the laparotomy group had disease recurrence, respectively (P = 0.12). Cox multivariate regression showed no statistically significant effect of surgical approach on overall survival (hazard ratio 1.50, P = 0.63) or on progression-free survival (hazard ratio 0.29, P = 0.07). Patients in the robotic cohort had significantly shorter median hospital stays (1 day vs. 7 days, P < 0.001), and their overall incidence of postoperative complications was lower (13% vs. 50%, P < 0.001). Median estimated blood loss for robotics was also significantly lower (82 mL vs. 528 mL, P < 0.001). CONCLUSION: Based on the data on a limited number of patients in a Canadian context, robotic radical hysterectomy did not lead to worse oncologic outcomes and was associated with improved short-term surgical outcomes. One might consider the evaluation of more personalized surgical decision making.


Assuntos
Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Quebeque/epidemiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
17.
J Obstet Gynaecol Res ; 45(12): 2386-2393, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31502321

RESUMO

AIM: To compare maternal and neonatal outcomes between the 'head first' and 'legs first' delivery methods during a second stage cesarean section. METHODS: We conducted a retrospective study between January 2009 and May 2015 at a large public university tertiary referral center. Included were all women who underwent cesarean delivery with a fully dilated cervix and a fetal head at the level of the ischial spines or below. The study population was divided into two groups according to way of fetal delivery: The 'legs first' (reverse breech) method and the 'head first' method. Demographics and maternal and fetal outcomes were retrieved for both groups. RESULTS: During the study period 447 women underwent a cesarean section while their cervix was fully dilated. Of them, 321 met the inclusion criteria: One hundred and twenty-one (38%) were delivered using the 'legs first' method and 200 (62%) were delivered using the 'head first' method. Indication for surgery and fetal head station was similar for both groups. While no difference in overall intraoperative uterine incision extension rate was observed, a higher rate of uterine incision extension was demonstrated in the 'head first' group in cases in which the second stage was longer than 180 min (33 vs 8 cases, P = 0.02). No differences in maternal postoperative complication rates and neonatal outcomes were observed. CONCLUSION: Fetal extraction via the 'legs first' method during prolonged second stage of labor may lower maternal morbidity. Method of delivery does not seem to have an effect on neonatal outcomes.


Assuntos
Apresentação Pélvica/cirurgia , Cesárea/métodos , Adulto , Extração Obstétrica , Feminino , Humanos , Recém-Nascido , Segunda Fase do Trabalho de Parto , Gravidez , Estudos Retrospectivos
19.
Gynecol Oncol ; 148(3): 553-558, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29395310

RESUMO

OBJECTIVE: The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens. STUDY DESIGN: RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival. RESULTS: In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively. CONCLUSION: Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Endometrioide/genética , Procedimentos Cirúrgicos de Citorredução , Terapia Neoadjuvante , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Ovarianas/genética , Reparo de DNA por Recombinação/genética , Hidrolases Anidrido Ácido , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Antígeno Ca-125/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Proteínas de Ciclo Celular/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Proteína do Grupo de Complementação C da Anemia de Fanconi/genética , Proteína do Grupo de Complementação F da Anemia de Fanconi/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/genética , Neoplasias Císticas, Mucinosas e Serosas/sangue , Neoplasias Císticas, Mucinosas e Serosas/tratamento farmacológico , Neoplasias Císticas, Mucinosas e Serosas/patologia , Proteínas Nucleares/genética , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ovariectomia , PTEN Fosfo-Hidrolase/genética , Prognóstico , Modelos de Riscos Proporcionais , Rad51 Recombinase/genética , Proteínas Repressoras/genética , Taxa de Sobrevida , Transcriptoma , Proteína Supressora de Tumor p53/genética
20.
J Obstet Gynaecol Can ; 40(12): 1571-1579, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30262383

RESUMO

OBJECTIVE: This study sought to evaluate the incidence, risk factors, and estimated cost associated with venous thromboembolism (VTE) following robotic surgery for endometrial cancer. METHODS: The study included all consecutive patients with newly diagnosed endometrial cancer who underwent robotic surgery, excluding patients with a previous history of VTE (3%), those taking long-term warfarin (3%), and patients with conversions to laparotomy (3%). The incidence of postoperative symptomatic VTE within 90 days was analyzed. Direct and indirect medical costs were estimated using a linked billing database for standardized, inflation-adjusted costs. RESULTS: A total of 558 cases were identified. Median BMI was 29 kg/m2 (range, 17-85 kg/m2), median operative time was 227 minutes (range, 75-419 minutes), and median blood loss was 30 mL (range, 3-400 mL). All patients received thromboprophylaxis with intraoperative subcutaneous heparin and sequential pneumatic compression devices. Extended postoperative prophylaxis for 28 days was administered to 88 (17.2%) patients with high-risk factors. A total of eight patients (1.6%) developed symptomatic VTE, and all eight were in the group that did not receive extended prophylaxis. The number needed to treat to prevent one VTE was 52.8, with an absolute risk reduction 1.89% (95% CI 0.59% to 3.19%). The average cost for treatment of a VTE was $7653 (range, $4396-$12 211), equivalent to the cost of treating 21 patients with extended prophylaxis ($356 per patient). CONCLUSION: The incidence of VTE in patients with endometrial cancer who underwent robotic-assisted surgery was low (1.6%), and none of the VTEs occurred in the cohort of high-risk patients who received extended thromboprophylaxis.


Assuntos
Neoplasias do Endométrio/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Custos e Análise de Custo , Bases de Dados Factuais , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Quebeque/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/economia , Tromboembolia Venosa/etiologia
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