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1.
Gynecol Oncol ; 185: 51-57, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38368813

RESUMO

OBJECTIVES: To compare surgical outcomes of patients with endometrial cancer who underwent robotic surgery across different BMI categories. METHODS: A retrospective study including all consecutive patients with endometrial cancer who underwent robotic surgery at a tertiary cancer center between December 2007 and December 2022. The study analyzed outcome measures, including blood loss, surgical times, length of hospitalization, perioperative complications, and conversion rates with the Kruskal-Wallis test for BMI group differences and the Chi-squared test for associations between categorical variables. RESULTS: A total of 1329 patients with endometrial cancer were included in the study. Patients were stratified by BMI: <30.0 (n = 576; 43.3%), 30.0-39.9 (n = 449; 33.8%), and ≥ 40.0 (n = 304; 22.9%). There were no significant differences in post-anesthesia care unit (PACU) stay (p = 0.105) and hospital stay (p = 0.497) between the groups. The rate of post-op complications was similar across the groups, ranging from 8.0% to 9.5% (p = 0.761). The rate of conversion to laparotomy was also similar across the groups, ranging from 0.7% to 1.0% (p = 0.885). Women with a BMI ≥40.0 had a non-clinically relevant but greater median estimated blood loss (30 mL vs. 20 mL; p < 0.001) and longer median operating room (OR) time (288 min vs. 270 min; p < 0.001). Within the OR time, the median set-up time was longer for those with a higher BMI (58 min vs. 50 min; p < 0.001). However, skin-to-skin time (209 min vs. 203 min; p = 0.202) and post-op time (14 min vs. 13 min; p = 0.094) were comparable between groups. CONCLUSION: BMI does not affect the peri-operative outcome of patients undergoing robotic staging procedures for endometrial cancer.


Assuntos
Índice de Massa Corporal , Neoplasias do Endométrio , Tempo de Internação , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Adulto
2.
CA Cancer J Clin ; 67(6): 493-506, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28881380

RESUMO

Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk-reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493-506. © 2017 American Cancer Society.


Assuntos
Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Testes Genéticos , Neoplasias Ovarianas/genética , Encaminhamento e Consulta , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
3.
Artigo em Inglês | MEDLINE | ID: mdl-38992749

RESUMO

STUDY OBJECTIVE: To characterize robotic surgery publications in gynecologic oncology, and to identify factors associated with high citation metrics. DESIGN: A cross-sectional study SETTING: Original articles on robotic surgery in gynecologic oncology. PATIENTS: No patients involved. INTERVENTIONS: Robotic surgeries in gynecologic oncology. MEASUREMENTS AND MAIN RESULTS: We performed PubMed MeSH search for original articles on robotic surgery in gynecologic oncology. We analyzed citation scores and income level of country of publication, as well as factors associated with high citation metrics. Overall, 566 studies during 2005 - 2023 were included. Of those 292, 51.6% were from North America and 182 32.2% from Europe. The leading tumor site studied was endometrial cancer (57.4%). The majority (87.6%) of studies were retrospective and 13 (2.3%) were randomized controlled trials. Most studies (94.2%) originated in high-income countries. Articles from middle-income countries had lower citations per year as compared to high-income countries (median 1.6 vs. 2.5, p=.002) and were published in lower impact factor journals (median 2.6 vs. 4.3, p<.001) when compared with high-income countries. Cervical cancer studies had higher representation in middle-income countries than in high income countries (48.5% vs. 18.4%, p<.001). In a multivariable regression analysis, journal's impact factor [aOR 95% CI 1.26 (1.12-1.40)], cervical cancer topic [aOR 95% CI 3.0 (1.58-5.91)] and North American publications [aOR 95% CI 2.07 (1.08-3.97)] were independently associated with higher number of citations per year. CONCLUSION: The majority of robotic surgery research in gynecologic oncology is retrospective and from high-income countries. Middle-income countries are not as frequently cited and are predominantly in lower impact factor journals.

4.
Arch Gynecol Obstet ; 309(6): 2381-2386, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38664269

RESUMO

Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This systematic literature review aims to provide an updated understanding of gynecologic PEComas based on available literature and data. Although PEComa is rare, there are varied tumor-site presentations across gynecologic organs, with uterine PEComas being the most prevalent. There is scarce high-quality literature regarding gynecologic PEComa, and studies on malignant PEComa underscore the challenges in diagnosis. Among the diverse mutations, mTOR alterations are the most prominent. Survival analysis reveals a high rate of local recurrence and metastatic disease, which commonly affects the lungs. Treatment strategies are limited, however mTOR inhibitors have pivotal role when indicated and chemotherapy may also be used. with some cases demonstrating promising responses. The paucity of data underscores the need for multicentric studies, an international registry for PEComas, and standardized reporting in case series to enhance clinical and pathological data.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias de Células Epitelioides Perivasculares , Humanos , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/diagnóstico , Inibidores de MTOR/uso terapêutico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/diagnóstico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Recidiva Local de Neoplasia/patologia
5.
Cancer Causes Control ; 34(6): 533-541, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36933150

RESUMO

PURPOSE: To investigate the association between alcohol intake over the lifetime and the risk of overall, borderline, and invasive ovarian cancer. METHODS: In a population-based case-control study of 495 cases and 902 controls, conducted in Montreal, Canada, average alcohol intake over the lifetime and during specific age periods were computed from a detailed assessment of the intake of beer, red wine, white wine and spirits. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between alcohol intake and ovarian cancer risk. RESULTS: For each one drink/week increment in average alcohol intake over the lifetime, the adjusted OR (95% CI) was 1.06 (1.01-1.10) for ovarian cancer overall, 1.13 (1.06-1.20) for borderline ovarian cancers and 1.02 (0.97-1.08) for invasive ovarian cancers. This pattern of association was similarly observed for alcohol intake in early (15- < 25 years), mid (25- < 40 years) and late adulthood (≥ 40 years), as well as for the intake of specific alcohol beverages over the lifetime. CONCLUSIONS: Our results support the hypothesis that a higher alcohol intake modestly increases the risk of overall ovarian cancer, and more specifically, borderline tumours.


Assuntos
Consumo de Bebidas Alcoólicas , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/etiologia , Fatores de Risco , Estudos de Casos e Controles , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/patologia , Cerveja
6.
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
7.
J Obstet Gynaecol ; 43(1): 2162866, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36689210

RESUMO

Endocervical sampling is performed traditionally with an endocervical curette (ECC). The current study objective is to compare the histopathological performance of endocervical brush (ECB) and endocervical curette (ECC). A retrospective review was performed including patients included that underwent colposcopy with endocervical sampling using either method. A total of 127 samples were obtained with ECC and 98 with ECB. Histopathological diagnosis was obtained in 124 (97.6%) ECC samples and in 94 (95.9%) ECB samples (p = 0.46). The incidence of benign results was similar between ECC and ECB (117 (92.1%) versus 88 (89.8%) respectively (p = 0.28)). When combining information from endocervical sampling with cervical biopsies, the detection rate of high-grade pathologies was similar between the groups with 14 cases (17.7%) for ECC and 8 cases (17.0%) for ECB (p = 0.43). A scope review of the topic was performed, illustrating that studies favour either method. In conclusion, ECB and ECC perform similarly for providing a histopathological diagnosis on endocervical samples.IMPACT STATEMENTWhat is already known on this subject? Endocervical samples in colposcopy were traditionally obtained using an endocervical curette. Similarly, a brush can be used for histological sampling of the endocervical canal. However, it is unclear how the ability to obtain a histopathological diagnosis compares between the two techniques.What do the results of this study add? This single-institution experience with using endocervical brush and curette for endocervical sampling finds that both methods are acceptable and have a high ability to provide a histopathological diagnosis. Precisely, 4.1% of brush and 2.4% of curette samples had insufficient tissue.What are the implications of these findings for clinical practice and further research? The endocervical brush is an adequate sampling method for colposcopy, and can be safely used instead of the curette, based on clinician preference. Further studies could investigate how these methods compare from a patient perspective.


Assuntos
Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Gravidez , Humanos , Colo do Útero/patologia , Esfregaço Vaginal/métodos , Manejo de Espécimes/métodos , Colposcopia , Curetagem , Neoplasias do Colo do Útero/patologia , Biópsia/métodos , Displasia do Colo do Útero/patologia
8.
J Surg Oncol ; 126(6): 1096-1103, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35819161

RESUMO

OBJECTIVE: To develop machine-learning models to predict recurrence and time-to-recurrence in high-grade endometrial cancer (HGEC) following surgery and tailored adjuvant treatment. METHODS: Data were retrospectively collected across eight Canadian centers including 1237 patients. Four models were trained to predict recurrence: random forests, boosted trees, and two neural networks. Receiver operating characteristic curves were used to select the best model based on the highest area under the curve (AUC). For time to recurrence, we compared random forests and Least Absolute Shrinkage and Selection Operator (LASSO) model to Cox proportional hazards. RESULTS: The random forest was the best model to predict recurrence in HGEC; the AUCs were 85.2%, 74.1%, and 71.8% in the training, validation, and test sets, respectively. The top five predictors were: stage, uterus height, specimen weight, adjuvant chemotherapy, and preoperative histology. Performance increased to 77% and 80% when stratified by Stage III and IV, respectively. For time to recurrence, there was no difference between the LASSO and Cox proportional hazards models (c-index 71%). The random forest had a c-index of 60.5%. CONCLUSIONS: A bootstrap random forest model may be a more accurate technique to predict recurrence in HGEC using multiple clinicopathologic factors. For time to recurrence, machine-learning methods performed similarly to the Cox proportional hazards model.


Assuntos
Neoplasias do Endométrio , Aprendizado de Máquina , Área Sob a Curva , Canadá/epidemiologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Estudos Retrospectivos
9.
Int J Cancer ; 148(9): 2304-2312, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197273

RESUMO

Guidelines for the treatment of tubo-ovarian cancer patients beyond third line are lacking. We aimed to evaluate the effect of response in each line on patient's outcome as well as identify variables that predict response for additional line of chemotherapy. A cohort study was performed including all patients with advanced high-grade ovarian cancer. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. Odds ratios and hazard ratios were calculated using multilevel, mixed-effects logistic regression and Cox regression, adjusting for repeated measures within individual patients. Two-hundred thirty-eight patients were included and underwent up to 10 lines of chemotherapy. The median progression-free survival was 15.6 and overall survival (OS) was 55.6 months. Response rates dropped with each additional line and by line 5, most patients (61%) became refractory and only 16% had any type of response (complete 4% or partial 12%). By line 2, whether a patient had partial disease (PR), stable disease (SD) or progressive disease (PD) did not have an effect on the OS. From line 2, whether a patient had PR, SD or PD did not have an effect on chemotherapy-free interval. Number of previous lines and time from previous line were the only variables that significantly correlated with both outcome of patients and response to the next line. In conclusion, time interval from the previous line of chemotherapy is the major clinical factor that predicts beneficial effect of another line of treatment in patients with ovarian cancer.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Idoso , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/mortalidade , Análise de Sobrevida
10.
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
11.
Am J Obstet Gynecol ; 225(4): 367.e1-367.e39, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34058168

RESUMO

OBJECTIVE: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). DATA SOURCES: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. STUDY ELIGIBILITY CRITERIA: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. METHODS: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4-43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%-73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I2=0%). CONCLUSION: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.


Assuntos
Adenocarcinoma de Células Claras/patologia , Carcinoma Endometrioide/patologia , Carcinossarcoma/patologia , Neoplasias do Endométrio/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Adenocarcinoma de Células Claras/cirurgia , Carcinoma Endometrioide/cirurgia , Carcinossarcoma/cirurgia , Corantes , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Verde de Indocianina , Excisão de Linfonodo , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/cirurgia
12.
J Pathol ; 252(1): 77-87, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558936

RESUMO

Atypical teratoid rhabdoid tumor (ATRT) is a fatal pediatric malignancy of the central neural system lacking effective treatment options. It belongs to the rhabdoid tumor family and is usually caused by biallelic inactivation of SMARCB1, encoding a key subunit of SWI/SNF chromatin remodeling complexes. Previous studies proposed that SMARCB1 loss drives rhabdoid tumor by promoting cell cycle through activating transcription of cyclin D1 while suppressing p16. However, low cyclin D1 protein expression is observed in most ATRT patient tumors. The underlying mechanism and therapeutic implication of this molecular trait remain unknown. Here, we show that SMARCB1 loss in ATRT leads to the reduction of cyclin D1 expression by upregulating MIR17HG, a microRNA (miRNA) cluster known to generate multiple miRNAs targeting CCND1. Furthermore, we find that this cyclin D1 deficiency in ATRT results in marked in vitro and in vivo sensitivity to the CDK4/6 inhibitor palbociclib as a single agent. Our study identifies a novel genetic interaction between SMARCB1 and MIR17HG in regulating cyclin D1 in ATRT and suggests a rationale to treat ATRT patients with FDA-approved CDK4/6 inhibitors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Ciclina D1/genética , Regulação Neoplásica da Expressão Gênica , Proteínas/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Teratoma/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Ciclina D1/metabolismo , Humanos , Proteínas/metabolismo , Tumor Rabdoide/metabolismo , Tumor Rabdoide/patologia , Proteína SMARCB1/metabolismo , Teratoma/metabolismo , Teratoma/patologia , Regulação para Cima
13.
Acta Obstet Gynecol Scand ; 100(3): 453-458, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33048344

RESUMO

INTRODUCTION: We compared oncologic and clinical outcomes in patients with advanced ovarian cancer who received dose-dense weekly paclitaxel with 3-weekly carboplatin with those who received standard 3-weekly chemotherapy. MATERIAL AND METHODS: Comparison of all consecutive patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer who received a dose-dense protocol between 2010 and 2016 with an immediate historical cohort of consecutive patients who received standard chemotherapy. Patients who received less than three cycles of treatment were excluded. RESULTS: In all, 246 patients were included in the study, of whom 128 received the dose-dense protocol and 118 were treated with the standard Q3-week protocol. Patients in the dose-dense group had significantly better progression-free survival than those receiving the standard protocol (median progression-free survival 22 vs 15 months; log rank = 0.026). The overall survival of patients in the dose-dense group was also better than that of the patients in the standard protocol group; however, this difference was not statistically significant (median overall survival 66 vs 54 months; log rank = 0.185). The dose-dense protocol remained significantly associated with favorable survival outcome in multivariable analysis adjusted for stage, histologic type, cytoreductive results and neoadjuvant chemotherapy. The use of the dose-dense protocol was associated with higher rates of gastrointestinal, dermatologic, neurologic and hematologic side effects. CONCLUSION: Despite the limitations associated with the comparison to a historical cohort, a dose-dense chemotherapy protocol resulted in a significantly improved progression-free survival and the overall survival tended to be better, but this difference did not reach statistical significance compared with the standard chemotherapy protocol, and may be considered as a treatment alternative, albeit with some increased side effects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Esquema de Medicação , Feminino , Humanos , Gradação de Tumores , Neoplasias Ovarianas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
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
15.
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
16.
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
17.
Int J Cancer ; 146(7): 1800-1809, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199510

RESUMO

Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate-to-vigorous recreational physical activity (MVPA) in relation to ovarian cancer risk. In a population-based case-control study conducted in Montreal, Canada from 2011 to 2016 (485 cases and 887 controls), information was collected on lifetime participation in various recreational physical activities, which was used to estimate MVPA for each participant. MVPA was represented as average energy expenditure over the lifetime and in specific age-periods in units of metabolic equivalents (METs)-hours per week. Odds ratios (OR) and 95% confidence intervals (CI) for the relation between average MVPA and ovarian cancer risk were estimated using multivariable logistic regression models. Confounding was assessed using directed acyclic graphs combined with a change-in-estimate approach. The adjusted OR (95% CI) for each 28.5 MET-hr/week increment of lifetime recreational MVPA was 1.11 (0.99-1.24) for ovarian cancer overall. ORs for individual age-periods were weaker. When examined by menopausal status, the OR (95% CI) for lifetime MVPA was 1.21 (1.00-1.45) for those diagnosed before menopause and 1.04 (0.89-1.21) for those diagnosed postmenopausally. The suggestive positive associations were stronger for invasive ovarian cancers and more specifically for high-grade serous carcinomas. These results do not support a reduced ovarian cancer risk associated with MVPA.


Assuntos
Exercício Físico , Atividades de Lazer , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco , Adulto Jovem
18.
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
19.
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
20.
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
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