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1.
Bull Cancer ; 107(3): 385-390, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115180

RESUMO

The group of rare malignant ovarian tumors includes the group of germ cell tumors, sex cords stromal ovarian tumors, small cell carcinoma, malignant Brenner tumors, rare epithelial tumors such as mucinous carcinoma, clear cell carcinoma, or low-grade serous carcinoma, as well as ovarian carcinosarcoma. Together they comprise about 10% of all ovarian tumors. Due to their low prevalence and their heterogeneity, data and treatment recommendations are limited. Even though all ovarian tumors are staged according to the FIGO staging of epithelial ovarian tumors, treatment differs especially in germ cell tumors and sex cords stromal ovarian tumors. Non-epithelial ovarian tumors can arise from a variety of ovarian precursor cells such as germ cells, granulosa cells, theca cells, or stromal fibroblasts. As can be expected already due to their divergent precursor lesions, these malignancies are substantially different but united by their rarity. This overview article gives a comprehensive summary on the pathology and clinical presentation, as well as therapy recommendations of a selection of those rare ovarian tumors, based on the latest national guidelines and related important publications.


Assuntos
Neoplasias Ovarianas , Doenças Raras , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Tumor de Brenner/patologia , Tumor de Brenner/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/terapia , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Doenças Raras/patologia , Doenças Raras/terapia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/terapia
3.
Int J Clin Oncol ; 25(3): 419-424, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020380

RESUMO

Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian carcinoma prevalent in Asians. No clear therapeutic selection based on molecular profile has been implemented for this disease. Oncogenic PIK3CA mutation, which activates the PIK3CA/AKT/mTOR signaling pathway, is a promising druggable alteration in OCCC. Recent studies by our group and others have identified the ARID1A mutation as another alteration linked to therapeutic selection based on synthetic lethality: deleterious ARID1A mutations, resulting in ARID1A deficiency, make OCCC cells sensitive to drugs targeting poly (ADP-ribose) polymerase and EZH2, as well as to glutathione inhibitors. In addition, we recently obtained evidence that ARID1A-deficient OCCC could benefit from gemcitabine treatment. Precision medicine based on gene alteration profiling might improve the prognosis of OCCC patients.


Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Medicina de Precisão/métodos , Adenocarcinoma de Células Claras/patologia , Antimetabólitos Antineoplásicos/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Proteínas de Ligação a DNA/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Dosagem de Genes , Glutationa/antagonistas & inibidores , Humanos , Terapia de Alvo Molecular/métodos , Mutação , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genética
4.
Int J Clin Oncol ; 25(3): 425-431, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989349

RESUMO

Ovarian clear cell carcinoma (OCCC), with unique clinical and molecular characteristics compared with other histological types of epithelial ovarian cancer (EOC), behaves like a distinct entity and has a poorer prognosis than other EOC types, especially in advanced stages. In addition, OCCC comprises approximately 27% of all EOC cases in Japan, compared with 12% in Western countries. Historically, patients with OCCC have been eligible for chemotherapeutic and surgical trials of EOC. It has been difficult to evaluate the specific impact of these trials on the prognosis of women with OCCC because of its rarity and unique molecular characteristics. Recent studies of OCCC revealed significant molecular variations related to carcinogenesis and molecular targets that could directly facilitate patient stratification and subsequent precision medicine. Thus, treatment strategies specific for OCCC based on its clinical and molecular characteristics are urgently needed. In this review, we highlight the management and treatment of OCCC from clinical aspects.


Assuntos
Adenocarcinoma de Células Claras/terapia , Neoplasias Ovarianas/terapia , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma de Células Claras/patologia , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Prognóstico
5.
Artigo em Inglês | MEDLINE | ID: mdl-31940991

RESUMO

Ovarian clear cell carcinoma (OCCC) is the second common histology of epithelial ovarian cancer in Taiwan. Stage IC is common, especially during minimally invasive surgery. Adjuvant chemotherapy in stage IC OCCC is unavoidable, and paclitaxel-based chemotherapy in Taiwan is self-paid. However, surgical spillage from minimally invasive surgery as a cause of unfavorable prognosis is still uncertain. The information of patients with stage IC OCCC, corresponding to a period of January 1995 to December 2016, was retrospectively collected following a chart and pathology review. Data regarding surgical methods, cytology status, regimens of adjuvant chemotherapy, survivorship, progression-free survival (PFS), and overall survival (OS) period were analyzed. In total, 88 patients were analyzed, and 64 and 24 patients were treated with paclitaxel- and nonpaclitaxel-based chemotherapy, respectively. Recurrence was identical between the two groups: PFS (47.5 ± 41.36 versus 54.0 ± 53.9 months, p = 0.157) and OS (53.5 ± 38.14 versus 79.0 ± 49.42 months, p = 0.070). Of the 88 patients, 12 had undergone laparoscopy for histological confirmation before complete open staging surgery; however, their PFS (49.5 ± 46.84 versus 49.0 ± 35.55 months, p = 0.719) and OS (56.5 ± 43.4 versus 51.0 ± 32.77 months, p = 0.600) were still comparable. Cytology results were only available for 51 patients, and positive washing cytology results seemed to worsen PFS (p = 0.026) but not OS (p = 0.446). In conclusion, adjuvant nonpaclitaxel chemotherapy and laparoscopic tumor spillage before the staging operation did not worsen the outcome in stage IC OCCC. Positive washing cytology has a negative effect on PFS but not on OS.


Assuntos
Adenocarcinoma de Células Claras , Antineoplásicos/uso terapêutico , Neoplasias Ovarianas , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adulto , Quimioterapia Adjuvante , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/uso terapêutico , Análise de Sobrevida
6.
Am J Obstet Gynecol ; 222(2): 170.e1-170.e11, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31421122

RESUMO

BACKGROUND: Patients ≥75 years old with ovarian cancer experience high perioperative morbidity, but recruitment into prospective trials to assess the role of surgery continues to be challenging. OBJECTIVE: To compare overall survival for patients ≥75 years old with ovarian cancer after chemotherapy alone vs neoadjuvant chemotherapy with interval cytoreductive surgery. STUDY DESIGN: Data were extracted from the National Cancer Data Base from 2004 to 2014. Kaplan-Meier and Cox proportional hazards models were used for statistical analyses. RESULTS: Of 1661 patients (median age: 79 years), most were white (88%) and had stage III-IV disease (95%), and 51% had serous histology. Of those who did not receive primary surgery, 58% had chemotherapy alone and the remainder had neoadjuvant chemotherapy with interval cytoreductive surgery. The use of neoadjuvant chemotherapy with interval cytoreductive surgery increased from 28% to 50% in years 2004-2007 to 2012-2014 (P<.001). Compared with neoadjuvant chemotherapy with interval cytoreductive surgery, chemotherapy-only patients were older (80 vs 78 years; P<.001) and had more advanced stage disease (98% vs 91%; P<.001). The 5-year overall survival of the entire study group was 14%; those who underwent neoadjuvant chemotherapy with interval cytoreductive surgery had overall survival of 25% compared with only 7% in chemotherapy alone group (P<.001). In multivariable analysis, neoadjuvant chemotherapy with interval cytoreductive surgery (hazard ratio, 0.44; 95% confidence interval, 0.36-0.54; P<.001) was an independent predictor for improved survival. Older (80-84 years) age (hazard ratio, 1.35; 95% confidence interval, 1.12-1.63; P=.002), advanced (stage III-IV) disease (hazard ratio; 2.06, 95% confidence interval, 1.37-3.09; P=.001), and clear cell histology (hazard ratio; 2.17, 95% confidence interval, 1.10-4.28; P=.03) portended for worse outcome. CONCLUSION: Patients ≥75 years with ovarian cancer old have an overall poor prognosis. Receiving neoadjuvant chemotherapy followed by interval cytoreductive surgery is associated with greater overall survival compared to chemotherapy alone.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/terapia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/terapia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais
7.
Am J Clin Oncol ; 43(2): 139-145, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31764020

RESUMO

Gynecologic clear cell carcinoma is a rare histology, accounting for ~5% of all ovarian and endometrial cancers in the United States. Compared to other types of gynecologic cancer, they are generally less responsive to standard therapy and have an overall worse prognosis. In addition, mounting evidence suggests that the landscape of genetic and molecular abnormalities observed in these tumors is distinct from other cancers that arise from the same sites of origin. On a molecular level, these tumors characteristically display upregulation of the PI3K-AKT-mTOR and RAS-RAF-MAPK signaling axes, frequent loss of ARID1a, and overexpression of MDM2. Evidence also suggests that these tumors are more likely to express programmed death ligand 1 or demonstrate microsatellite instability than other gynecologic cancers. Despite these important differences, there has been relatively little investigation into histology-specific treatment of clear cell gynecologic cancers, representing an opportunity for new drug development. In this article, we review the unique genetic and molecular features of gynecologic clear cell cancers with an emphasis on potential therapeutic targets. The results of completed studies of treatment for clear cell carcinoma are also presented. We conclude with a discussion of ongoing clinical trials and potential avenues for future study.


Assuntos
Adenocarcinoma de Células Claras/genética , Neoplasias dos Genitais Femininos/genética , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Antineoplásicos Imunológicos/uso terapêutico , Variações do Número de Cópias de DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/metabolismo , Neoplasias dos Genitais Femininos/patologia , Fator 1-beta Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/metabolismo , Humanos , Instabilidade de Microssatélites , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Terapia de Alvo Molecular , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Quinases raf/genética , Quinases raf/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismo
8.
Gynecol Oncol ; 156(1): 62-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31776037

RESUMO

OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.


Assuntos
Adenocarcinoma de Células Claras/cirurgia , Algoritmos , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Adenocarcinoma de Células Claras/patologia , Idoso , Estudos de Coortes , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento
9.
Gynecol Oncol ; 156(1): 154-161, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759772

RESUMO

OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Adulto Jovem
10.
In Vivo ; 34(1): 177-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882477

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is the major gynecological cause of cancer deaths. Annexin A1 (ANXA1) protein has been implicated in the aggressiveness of several cancer types. MATERIALS AND METHODS: This study retrospectively assessed ANXA1 expression in epithelial cells of 156 pre-chemotherapy EOC samples and 34 normal ovarian samples from patients treated at Salah Azaiez Institute. Using immunohistochemistry, ANXA1 expression was compared in normal versus cancer samples; correlations with clinicopathological features, including overall survival, were sought. RESULTS: Fifty-two percent of tumor samples showed epithelial ANXA1 staining versus only 26% of normal samples (Fisher's exact test, p=0.00794). Epithelial ANXA1 expression was correlated with better overall survival in both univariate and multivariate analyses. CONCLUSION: The possible contribution of ANXA1 overexpression to EOC outcome may be relevant to therapeutic strategies.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Anexina A1/metabolismo , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
In Vivo ; 34(1): 397-400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882505

RESUMO

BACKGROUND/AIM: Ovarian cancer presents an aggressive tumor biology, a significant number of patients experiencing recurrent disease. The aim of this study was to examine the feasibility and effectiveness of secondary debulking surgery for relapsed ovarian cancer. PATIENTS AND METHODS: Between 2014 and 2018, debulking surgery for relapsed ovarian cancer was performed in 40 cases. RESULTS: Debulking surgery to no residual disease was achieved in 31 cases; among the remaining cases, an R1 resection was feasible in six cases, while in the remaining three cases an R2 resection was performed. The most commonly performed visceral resections were represented by rectosigmoidian resection, right colon resection, total or partial cystectomy and unilateral or bilateral ureteral resection. The early postoperative morbidity rate was 32.5% while the postoperative mortality rate was 2.5%. CONCLUSION: Extended pelvic resections are feasible in patients with relapsed ovarian cancer and might be performed with acceptable rates of postoperative complications.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Pélvicas/cirurgia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Neoplasias Pélvicas/patologia , Prognóstico , Estudos Retrospectivos
12.
In Vivo ; 34(1): 407-411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882507

RESUMO

BACKGROUND/AIM: The role of upper abdominal resection as part of debulking surgery for advanced-stage or relapsed ovarian cancer has been widely debated. The aim of this study was to investigate the safety and efficacy of upper abdominal resection as part of tertiary cytoreduction. PATIENTS AND METHODS: Between 2005 and 2019, 11 cases presenting upper abdominal recurrences after surgically treated ovarian cancer were submitted to surgery with radical intent. RESULTS: Complete debulking surgery was feasible in eight cases, optimal debulking was performed in two cases, while in one case a suboptimal resection was performed. The most commonly performed upper abdominal resections consisted of liver resection in seven cases, splenectomy in four cases, diaphragmatic resection in three cases, pancreatic tail resection in two cases and partial gastrectomy in another two cases. Postoperative complications were encountered in two cases, while postoperative mortality was null. CONCLUSION: Extended upper abdominal resection can be safely performed in order to increase the chances of optimal debulking surgery at the time of tertiary cytoreduction.


Assuntos
Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias do Endométrio/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Idoso , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos
13.
Anticancer Res ; 39(11): 5953-5962, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704820

RESUMO

BACKGROUND/AIM: The presence of ascites in ovarian cancer patients is considered a negative prognostic factor. The underlying mechanisms are not clearly understood. MATERIALS AND METHODS: The amount of ascites was evaluated, preferably, using diffusion-weighted MRI at primary diagnosis in a retrospective cohort of 214 women with ovarian cancer, in an ordinal manner (amount of ascites: none, limited, moderate, abundant). In a prospective cohort comprising 45 women with ovarian cancer, IL-10 (interleukin), VEGF (vascular endothelial growth factor), TGF-ß (transforming growth factor) and CCL-2 [chemokine (C-C) motif ligand 2] were measured at diagnosis (and at interval debulking, when available). RESULTS: Gradually increasing amounts of ascites were correlated significantly, even after correction for FIGO stage, with reduced survival (p<0.0001) and stronger immunosuppression (IL10 and VEGF). Neoadjuvant chemotherapy reduced immunosuppression, which was observed as a reduction in CCL-2, IL-10 and VEGF. CONCLUSION: The amount of ascites is an independent predictor of survival and correlates with increased immunosuppression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ascite/mortalidade , Imunossupressão/mortalidade , Terapia Neoadjuvante/efeitos adversos , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/imunologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Ascite/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
14.
Eur J Obstet Gynecol Reprod Biol ; 243: 120-124, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31689674

RESUMO

OBJECTIVE: To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure. STUDY DESIGN: An Israel Gynecologic Oncology Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups. RESULTS: There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12-120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p = 0.53), disease-specific survival (93.4% vs. 91.7%; p = 0.5), and overall survival (86.2% vs. 80.6%; p = 0.22). CONCLUSION: Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.


Assuntos
Adenocarcinoma de Células Claras/diagnóstico , Carcinoma Endometrioide/diagnóstico , Carcinossarcoma/diagnóstico , Neoplasias do Endométrio/diagnóstico , Histeroscopia/estatística & dados numéricos , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Idoso , Biópsia , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Curetagem , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Histerectomia , Israel , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Salpingo-Ooforectomia
15.
J Cancer Res Clin Oncol ; 145(11): 2737-2749, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586262

RESUMO

BACKGROUND: Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer. MATERIALS AND METHODS: We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay). RESULTS: The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity. CONCLUSION: These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Proliferação de Células , Estudos de Coortes , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
16.
In Vivo ; 33(6): 2299-2302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662571

RESUMO

BACKGROUND/AIM: Clear cell vaginal adeno-carcinomas are rare tumors occurring in women which are usually treated by chemo radiotherapy with good outcomes. However, in certain cases, this treatment is not associated with complete response and a further surgery is needed. CASE REPORT: We present the case of a 38-year-old patient diagnosed with stage IVA clear cell vaginal cancer who had been previously submitted to radio chemotherapy and in whom the lesion persisted after the oncological treatment; therefore, the patient was proposed for surgery with curative intent. The tumor was resected by performing an anterior pelvic exenteration with good outcomes, the patient being discharged in the seventh postoperative day. At one-year follow-up the patient remains free of recurrent disease. CONCLUSION: Pelvic exenteration with curative intent might be the option of choice for persistent locally advanced clear cell vaginal cancer.


Assuntos
Adenocarcinoma de Células Claras/terapia , Exenteração Pélvica , Neoplasias Vaginais/terapia , Adenocarcinoma de Células Claras/etiologia , Adenocarcinoma de Células Claras/patologia , Adulto , Carcinógenos , Quimiorradioterapia , Dietilestilbestrol/efeitos adversos , Feminino , Humanos , Exenteração Pélvica/métodos , Resultado do Tratamento , Neoplasias Vaginais/diagnóstico , Neoplasias Vaginais/etiologia
17.
Obstet Gynecol ; 134(5): 1017-1026, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31599824

RESUMO

OBJECTIVE: To examine the incidence and prognostic effects of intraoperative capsule rupture and to assess the effectiveness of postoperative chemotherapy for intraoperative tumor rupture in apparent stage I epithelial ovarian cancer. METHODS: This is a society-based retrospective observational study in Japan that examined 15,163 women with stage IA-IC1 epithelial ovarian cancer who underwent primary surgical treatment between 2002 and 2015. Associations between intraoperative capsule rupture and cause-specific survival, and between postoperative chemotherapy and cause-specific survival among intraoperatively ruptured cases were examined by histology type (clear cell n=6,107, endometrioid n=3,910, mucinous n=3,382, and serous n=1,764). RESULTS: Clear cell histology had the highest risk of intraoperative capsule rupture (57.3%), followed by endometrioid (48.8%), serous (41.8%), and mucinous (32.0%) histologies (P<.001). On multivariable analysis, clear cell type exhibited the largest effect of intraoperative capsule rupture on cause-specific survival (adjusted hazard ratio [HR] 1.99, 95% CI 1.45-2.75), followed by serous (adjusted HR, 1.61, 95% CI 0.84-3.11), mucinous (adjusted HR 1.28, 95% CI 0.79-2.09), and endometrioid (adjusted HR, 1.14, 95% CI 0.64-2.01) tumors. Postoperative chemotherapy for intraoperatively ruptured cases did not improve cause-specific survival in any histologic types in multivariable analysis: clear cell, adjusted HR 0.86, 95% CI 0.56-1.31; serous, adjusted HR 1.08, 95% CI 0.42-2.74; mucinous, adjusted HR 1.11, 95% CI 0.55-2.27; and endometrioid, adjusted HR 2.81, 95% CI 0.85-9.30 (all, P>.05). In the cohort-level analysis of ruptured cases (n=7,227), postoperative chemotherapy use has significantly decreased in mucinous (16.3% relative decrease), endometrioid (13.1% relative decrease), and clear cell (9.3% relative decrease) (all, P<.05); but, the cohort-level 5-year cause-specific survival rate did not change over time (all, P>.05). CONCLUSION: Among apparent stage I epithelial ovarian cancer, the clear cell type possesses a disproportionally high risk of capsule rupture during adnexectomy and is associated with the most adverse effect on survival. A decrease in the use of postoperative chemotherapy for intraoperatively ruptured cases in Japan is likely the result of increasing awareness of the absence of survival benefits.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Complicações Intraoperatórias , Neoplasias Ovarianas , Ruptura , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Humanos , Incidência , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/patologia , Complicações Intraoperatórias/terapia , Japão/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Ruptura/epidemiologia , Ruptura/etiologia , Ruptura/patologia , Ruptura/terapia , Análise de Sobrevida , Resultado do Tratamento
18.
J Med Case Rep ; 13(1): 314, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31639046

RESUMO

BACKGROUND: To determine the prevalence of and risk factors for malignant transformation of ovarian endometrioma during dienogest therapy, which is very rare, we examined multiple cases of malignant transformation of ovarian endometrioma during dienogest therapy and performed a multivariate analysis of the records in our hospital. METHODS: The medical records of 174 patients who underwent DNGT for the treatment of OMA from June 1, 2011, to May 31, 2018, were reviewed retrospectively with the approval of the Human Ethical Committee of the University of Teikyo Hospital. And we provided one representative case of MT with obtaining written informed consent. To assess the effects of six representative factors, including advanced age, parity, surgical history, and endometrial cyst characteristics (including 3 factors), on the possibility of malignant transformation, we performed a multivariate logistic regression analysis. RESULTS: Of the 174 cases, 4 were diagnosed with malignant transformation, and these cases are reported. In the multivariate analysis, advanced age (P = 0.0064), nullipara (P = 0.0322), and enlargement (P = 0.0079) showed significant differences for malignant transformation occurrence. All 4 malignant transformation cases were among the 19 patients who had all of these 3 factors. CONCLUSIONS: For a more accurate determination of the treatment approach, a larger sample size will be needed to determine the risk factors for malignant transformation during dienogest therapy.


Assuntos
Transformação Celular Neoplásica , Anticoncepcionais Orais Hormonais/efeitos adversos , Endometriose/patologia , Nandrolona/análogos & derivados , Doenças Ovarianas/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/patologia , Adulto , Fatores Etários , Endometriose/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Nandrolona/efeitos adversos , Doenças Ovarianas/tratamento farmacológico , Paridade , Estudos Retrospectivos , Fatores de Risco
20.
Radiat Oncol ; 14(1): 173, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585543

RESUMO

BACKGROUND: Ultrasound (US) imaging has been proved as an excellent diagnostic tool in gynecology and, due to its wide availability and limited cost, is under intense investigation as base for dose adaptation in cervical cancer brachytherapy. Purpose of this work is to test inter/intra-observer uncertainties between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) imaging in defining maximum tumor width before first brachytherapy (BT) application in a prospective cohort of cervical cancer patients undergoing image-guided adaptive brachytherapy (IGABT). METHODS: One hundred ten consecutive cervical cancer patients treated between 2013 and 2016 were included. Before the first BT implant patients underwent MR and TRUS scan with no applicator in place. Images were independently analyzed by three examiners, blinded to the other's results. With clinical information at hand, maximum tumor width was measured on preBT TRUS and MR. Quantitative agreement analysis was undertaken. Intra-class correlation coefficient (ICC), Passing-Bablok and Bland Altman plots were used to evaluate the intra/inter-observers measurement agreement. RESULTS: Average difference between tumor width measured on MR (HRCTVMR) and TRUS (HRCTVTRUS) was 1.3 ± 3.2 mm (p <  0.001); 1.1 ± 4.6 mm (p = 0.01) and 0.7 ± 3 mm (p = 0.01). The error was less than 3 mm in 79, 82 and 80% of the measurements for the three observers, respectively. Intra-observer ICC was 0.96 (CI95% 0.94-0.97), 0.93 (CI95% 0.9-0.95) and 0.96 (CI95% 0.95-0.98) respectively. Inter-observer ICC for HRCTVMR width measures was 0.92 (CI95% 0.89-0.94) with no difference among FIGO stages. Inter-observer ICC for HRCTVTRUS was 0.86 (CI95% 0.81-0.9). For FIGO stage I and II tumors, ICC HRCTVTRUS values were comparable to respective HRCTVMR ICC values. For larger tumors HRCTVTRUS inter-observer ICC values were lower than respective HRCTVMR although remaining acceptable. CONCLUSIONS: Our results suggest that TRUS is equivalent to MR in assessing preBT tumor maximum width in cervical cancer FIGO stage I/II. In more advanced stages TRUS seems to be slightly inferior to MR although maintaining a good agreement to gold standard imaging.


Assuntos
Braquiterapia , Imagem por Ressonância Magnética/métodos , Variações Dependentes do Observador , Ultrassonografia/métodos , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias do Colo do Útero/radioterapia , Adulto Jovem
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