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1.
Zhonghua Fu Chan Ke Za Zhi ; 55(12): 848-856, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33355760

RESUMO

Objective: To investigate the diagnosis, treatment and prognosis of uterine serous carcinoma (USC), and further analyze the prognostic factors. Methods: USC patients who underwent surgery with complete follow-up at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: (1) Diagnosis and treatment: the study included 71 USC patients. Only 32 patients (45%, 32/71) were diagnosed preoperatively with USC, and 25 cases of them (35%, 25/71) underwent USC standard comprehensive staging surgery. Of the 25 patients, 10 cases (40%, 10/25) had up-staged after operation. (2) Prognosis: the 5-year disease free survival (DFS) rate and overall survival (OS) rate for all patients were 76.5% and 80.6%, respectively. (3) The results of prognostic factors analysis: univariate analysis on age, range of lymphadenectomy, peritoneal cytology, the depth of myometrial invasion, adnexal and (or) serosa involvement and omentum metastasis were significantly associated with 5-year DFS rate (all P<0.05); range of lymphadenectomy, range of surgical staging, peritoneal cytology, adnexal and (or) serosa involvement and postoperative adjuvant treatment were significantly associated with 5-year OS rate (all P<0.05). Multivariate analysis on range of surgical staging (HR=5.18, 95%CI: 1.04-25.70, P=0.044) and adnexal and (or) serosa involvement (HR=8.41, 95%CI: 2.28-31.05, P=0.001) were independent prognostic factors for 5-year DFS rate; range of lymphadenectomy [no lymphadenectomy vs pelvic lymphadenectomy (PLN)+para-aortic lymphadenectomy (PALN), HR=27.76, 95%CI: 1.76-437.78, P=0.018;PLN vs PLN+PALN, HR=5.98, 95%CI: 1.11-32.27, P=0.038] and peritoneal cytology (HR=5.47, 95%CI: 1.18-25.39, P=0.030) were independent prognostic factors for 5-year OS rate. Conclusions: The preoperative pathological diagnosis of USC is difficult, resulting in incomplete surgical staging and inaccurate staging. Range of surgical staging, adnexal and (or) serosa involvement, peritoneal cytology and range of lymphadenectomy are independent prognostic factors, which deserve much attention in clinical practice.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos em Ginecologia/métodos , Terapia Neoadjuvante/métodos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , China/epidemiologia , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Prognóstico , Estudos Retrospectivos , Neoplasias Uterinas/mortalidade
3.
Rev Mal Respir ; 37(4): 341-345, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32284205

RESUMO

In systemic sclerosis, the presence of an anti-RNA polymerase III antibody (ARNpol3) is associated with an increased risk of cancer. The characteristic picture of this serotype includes severe diffuse cutaneous involvement, a high risk of renal scleroderma crisis and a 10 year survival of only around 30%. Pulmonary involvement is less common. We report the case of a woman initially treated for drug-induced acute interstitial lung disease revealing chronic interstitial pneumonia with autoimmune features. The disease evolved in three stages with the occurrence of a rapidly progressive diffuse skin sclerosis with anti-ARNPol3 antibodies in the context of ovarian cancer remission.


Assuntos
Cistadenocarcinoma Seroso/complicações , Flecainida/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Ovarianas/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Idoso , Autoanticorpos/sangue , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , RNA Polimerase III/imunologia , Indução de Remissão , Escleroderma Sistêmico/sangue
4.
BMC Cancer ; 20(1): 185, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131779

RESUMO

BACKGROUND: To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). METHODS: We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. RESULTS: BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients. CONCLUSION: In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Cistadenocarcinoma Seroso/terapia , Tratamento Farmacológico/métodos , Mutação em Linhagem Germinativa , Procedimentos Cirúrgicos em Ginecologia/métodos , Neoplasias Ovarianas/terapia , Adulto , Idoso , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
5.
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
6.
Gynecol Oncol ; 157(1): 46-54, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32008792

RESUMO

OBJECTIVE: Low-grade serous carcinoma (LGSC) is a rare histotype of ovarian cancer with a unique disease course. Little data exist regarding the influence of sociodemographic factors on diagnosis and outcomes in this disease. Our objective was to evaluate the associations between these factors and the clinical characteristics, treatment approaches, and survival in LGSC. METHODS: The National Cancer Database (NCDB) was queried for data between 2004 and 2015 on patients with LGSC. LGSC was inclusive of invasive, grade 1, serous carcinoma of the ovary, fallopian tube, or peritoneum. Patient demographics, insurance status, disease characteristics, treatment approach, and survival were evaluated. ANOVA, Chi Square, Kaplan-Meier, and Cox regression were used in the analysis. RESULTS: 3221 patients with LGSC were evaluated (89.5% White, 6.2% Black; 7.2% Hispanic, 92.8% non-Hispanic). Compared to Whites, Blacks were diagnosed younger (50.4 vs. 55.9 years, p < 0.01), received less chemotherapy (61.8% vs 67.0%, p = 0.04), and had less CA-125 elevation (OR 4.14 [1.26-13.57], p = 0.02). Compared to non-Hispanics, Hispanics were younger (49.5 vs. 55.8 years, p < 0.01) and received less chemotherapy (55% vs 67%, p < 0.001). In contrast to private insurance, government insurance was associated with a higher 30-day mortality (1.5% vs 0.01%, p < 0.001). Race/ethnicity were not predictive of OS, while older age (HR 1.013 [1.002-1.024], p = 0.03), advanced stage (HR 3.09 [2.15-4.43], p < 0.001), and government insurance (HR 2.33 [1.65-3.30], p < 0.001) were all independently associated with worse OS. CONCLUSIONS: Significant differences exist in the clinical characteristics, treatments, and outcomes of LGSC by sociodemographics, with Blacks and Hispanics being diagnosed younger and receiving less chemotherapy. Age, stage, and insurance status were predictive of overall survival.


Assuntos
Cistadenocarcinoma Seroso/etnologia , Cistadenocarcinoma Seroso/terapia , Disparidades em Assistência à Saúde/etnologia , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/terapia , Adolescente , Adulto , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/economia , Cistadenocarcinoma Seroso/patologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Humanos , Cobertura do Seguro , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Neoplasias Ovarianas/economia , Neoplasias Ovarianas/patologia , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
7.
Gynecol Oncol ; 157(2): 340-347, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32067813

RESUMO

OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.


Assuntos
Cistadenocarcinoma Seroso/genética , Neoplasias Uterinas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sequência de RNA , Análise Serial de Tecidos , Transcriptoma , Células Tumorais Cultivadas , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia
8.
Gynecol Oncol ; 156(3): 715-725, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31969252

RESUMO

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Animais , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Aust N Z J Obstet Gynaecol ; 60(1): 27-33, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31849044

RESUMO

BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a unique entity with clinical and molecular characteristics distinct from high-grade serous ovarian carcinoma (HGSOC). To date the majority of research has focused on the more common HGSOC, with treatment recommendations often extrapolated to LGSOC. Women with LGSOC are typically diagnosed younger and have indolent and relatively chemoresistant disease. Recently there have been major research advances in LGSOC. AIMS: This systematic review describes the epidemiological, clinical and molecular characteristics of LGSOC, with advances in research and novel treatment options also discussed. MATERIALS AND METHODS: A 10-year comprehensive systematic review of peer-reviewed literature was conducted, with a total of 132 abstracts read, 89 articles reviewed and 49 included in this review. RESULTS: This review highlights the clinical and molecular features of LGSOC, current and traditional treatment options and areas of current research into targeted agents. CONCLUSIONS: Our growing knowledge about LGSOC as a distinct clinical and molecular entity from HGSOC has led to the investigation of more targeted and tailored therapies as their clinical course, optimal management and therapeutic targets differ. There is a need for ongoing collaborative research to provide better treatment options for these patients.


Assuntos
Carcinoma Epitelial do Ovário/epidemiologia , Cistadenocarcinoma Seroso/epidemiologia , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/terapia , Feminino , Preservação da Fertilidade , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/epidemiologia
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.
Gynecol Oncol ; 156(2): 415-422, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785864

RESUMO

OBJECTIVE: High-grade serous ovarian cancers (HGSOC) are genomically characterized by homologous recombination deficiency (HRD) and TP53 mutations, which lead to intratumor heterogeneity (ITH). This study aimed to reveal the relationship between HRD, ITH and prognosis and analyze their changes during treatment. METHODS: We obtained 573 SNP array and gene expression array data from The Cancer Genome Atlas. SNP array data were processed to calculate the Clonality Index (CI) and loss of heterozygosity (LOH) scores. Gene expression array data were used for classifying molecular subtypes. Additionally, we obtained 33 samples from 20 HGSOC patients, including 4 samples from interval debulking surgery (IDS) and 9 samples from recurrent surgery. RESULTS: We divided HGSOC samples into 2 groups. The high CI group showed a high recurrent risk, and the high LOH group showed a statistically good prognosis. Combining the two factors, the high LOH/low CI group showed a statistically good prognosis. In terms of molecular subtypes, the mesenchymal subtype, which had a poor prognosis, showed a high CI with statisitically significant difference and the immunoreactive subtype, which had a good prognosis, showed a tendency to have a high LOH score. Throughout treatment, the CI decreased to one at the IDS (n = 4) and then increased at recurrence (n = 3). LOH scores greatly decreased in two cases at the IDS. CONCLUSIONS: ITH and HRD were associated with prognosis in HGSOC. ITH decreased after neoadjuvant chemotherapy, suggesting that the chemo-resistant cancer clone remains after chemotherapy.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/patologia , Procedimentos Cirúrgicos de Citorredução , Feminino , Recombinação Homóloga , Humanos , Perda de Heterozigosidade , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transcriptoma
12.
Int J Cancer ; 146(7): 1851-1861, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603993

RESUMO

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/genética , Ovário/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclo Celular/genética , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genômica , Humanos , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Terapia Neoadjuvante/métodos , Neoplasia Residual , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Ovariectomia/métodos , Ovário/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Análise de Sobrevida , Serina-Treonina Quinases TOR/metabolismo
13.
J Obstet Gynaecol Res ; 46(1): 153-160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642140

RESUMO

AIM: Serous carcinoma of the uterine cervix (USCC) is a very rare malignant tumor, while this histological subtype is common in the ovary, fallopian tube, uterine corpus and peritoneum. Because of its rarity, details of the clinicopathological features of USCC are largely unknown. We retrospectively analyzed the clinicopathological characteristics of five cases of pure USCC. METHODS: We reviewed the medical records and pathological specimens of five USCC cases who were treated at the Gynecology Service of the National Hospital Organization Kyushu Cancer Center, Japan, between 2000 and 2017. The clinicopathological features were also compared with those of serous carcinomas of the endometrium and ovary who were treated during the same period. RESULTS: Five patients were treated at our hospital between 2000 and 2017. Three tumors were stage IB1, one was stage IIB, and one was stage IVB. The median follow-up time was 104 months (range 26-210). Four patients other than stage IVB were treated with radical hysterectomy and have been free of relapse. One patient with stage IVB tumor was treated with platinum-based combination chemotherapy and is currently on maintenance therapy with bevacizumab and remains free of relapse. CONCLUSION: USCC has a distinctive clinicopathological feature that differentiates it from serous carcinomas of other female organs. USCC had been thought to be a poor prognostic disease; however, it could be curable if it is not accompanied by lymph node metastasis or peritoneal dissemination. We might conquer USCC even if it is accompanied by lymph node metastasis with the use of multimodal therapy.


Assuntos
Cistadenocarcinoma Seroso/patologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Colo do Útero/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/terapia
14.
Neurol India ; 67(6): 1431-1436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31857529

RESUMO

Aims and Objectives: To review a series of patients with brain metastases from ovarian cancer at a single institution. To describe treatment modalities, their outcomes and to determine prognostic factors. Patients and Methods: Between January 1995 and December 2014, 25 patients with ovarian cancer brain metastases were treated at The Sheba Medical Center. The medical records were retrospectively reviewed to collect demographic, clinical, and imaging data as well as the information on the treatment modalities used and their outcomes. Results: Mean patient age at the time of brain metastasis diagnosis was 62.7 years. The median interval between the diagnosis of primary cancer and brain metastasis was 42.3 months. Neurologic deficits, headache, and seizure were the most common symptoms. The brain was the only site of metastasis in 20% of the patients. Active ovarian cancer at the time of diagnosis of brain metastasis was observed in half of the patients with systemic disease. Multiple brain metastases were observed in 25% of the patients. We treated 11 patients with surgery plus radiation therapy protocols in various orders: surgery followed by complementary whole-brain radiation therapy (WBRT), surgery followed by stereotactic radiosurgery (SRS), and surgery followed by WBRT and then by adjuvant SRS. Five patients underwent surgery alone and nine patients were treated with radiation alone (WBRT, SRS, or both). Univariate analysis for predictors of survival demonstrated that age above 62.7 years at the time of central nervous system involvement was a significant risk factor and leptomeningeal disease was a poor prognostic factor in reference to supra-tentorial lesions. Multivariate analysis for predictors of survival, however, showed that multiple brain lesions (>4) were a poor prognostic factor, and multivariate analysis of the time to progression revealed that combined treatments of surgery and radiation resulted in longer median periods of progression-free survival than each modality alone. Conclusion: We conclude that the only significant predictors of survival or progression-free survival in our cohort were the number of brain metastases and the treatment modality.


Assuntos
Neoplasias Encefálicas/secundário , Irradiação Craniana , Cistadenocarcinoma Seroso/secundário , Procedimentos Neurocirúrgicos , Neoplasias Ovarianas/patologia , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
Anticancer Drugs ; 30(10): 1064-1066, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567308

RESUMO

Heavily pretreated ovarian cancer patients become progressively chemoresistant, and thereafter, only scant treatments potentially accord reasonable, albeit limited clinical efficacy. We describe a case involving a 67-year-old ovarian cancer patient who underwent multiple lines of chemotherapy and presented with recurrent disease and a CA-125 of 4112 U/mL. Thenceforth, she was treated with GL-ONC1 oncolytic viral therapy that was administered laparoscopically in accordance with a clinical trial. The patient subsequently received chemotherapy and during the fourth cycle, her CA-125 decreased to 99 U/mL; moreover, a computed tomography scan of the pelvis exhibited significant disease reduction. Viral therapy hypothetically confers significant promise in the treatment of recurrent ovarian cancer, especially in patients who remain unresponsive to traditional medications.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/terapia , Terapia Viral Oncolítica/métodos , Neoplasias Ovarianas/terapia , Vírus Vaccinia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno Ca-125/sangue , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Laparoscopia , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Derrame Pleural/etiologia , Tomografia Computadorizada por Raios X
16.
Cancer Immunol Immunother ; 68(11): 1747-1757, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602489

RESUMO

BACKGROUND: Immunotherapy has become a powerful treatment option for several solid tumor types. The presence of tumor-infiltrating lymphocytes (TIL) is correlated with better prognosis in ovarian cancer, pointing at the possibility to benefit from harnessing their anti-tumor activity. This preclinical study explores the feasibility of adoptive cell therapy (ACT) with TIL using an improved culture method. METHODS: TIL from high-grade serous ovarian cancer were cultured using a combination of IL-2 with agonistic antibodies targeting 4-1BB and CD3. The cells were phenotyped using flow cytometry in the fresh tissue and after expansion. Tumor reactivity was assessed against HLA-matched ovarian cancer cell lines via IFN-γ ELISPOT. RESULTS: Ovarian cancer is highly infiltrated with CD8+ TIL that are preferentially and robustly expanded with the addition of the agonistic antibodies. With a 95% success rate, the TIL are grown to ≥ 100 × 106 cells in 2-3 weeks without over differentiation. In addition, the CD8+ TIL grown with this method showed HLA-restricted tumor recognition. CONCLUSIONS: These results indicate the viability of TIL ACT for refractory ovarian cancer by allowing for the large expansion of anti-tumor TIL in a short time and consistent manner.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Quimiorradioterapia , Cistadenocarcinoma Seroso/terapia , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Ovarianas/terapia , Terapia de Salvação , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/secundário , Citotoxicidade Imunológica/imunologia , Feminino , Seguimentos , Humanos , Ativação Linfocitária , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico
17.
J Surg Oncol ; 120(7): 1208-1219, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531879

RESUMO

BACKGROUND: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial. METHODS: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up. RESULTS: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients. CONCLUSION: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Peritônio/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Quimioterapia Adjuvante , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/terapia , Estudos Retrospectivos , Taxa de Sobrevida
18.
BMC Cancer ; 19(1): 748, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362708

RESUMO

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely uncommon malignancy exclusively reported in females. Due to the rarity of the disease, it is difficult to establish a standardized treatment. CASE PRESENTATION: We describe a unique case of PRSA in a 71-year-old male who presented with right-sided lower back pain and numbness. Magnetic resonance imaging identified a mass invading the adjacent psoas muscle and twelfth rib. Tissue biopsy confirmed poorly differentiated PRSA. Patient was initially treated with neoadjuvant carboplatin and paclitaxel chemotherapy regimen. This resulted in complete radiological resolution of the tumor. However, 12 weeks later, rapid recurrence was noted on follow-up CT scan. The patient was then treated with external radiotherapy with concurrent nivolumab, an anti-PD-1 antibody. The patient displayed a positive response to treatment with reduction in primary tumor and metastases and had a sustained disease control. CONCLUSION: Treatment with radiotherapy in combination with anti-PD-1 antibody could be an effective modality of management for PRSA.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/terapia , Imunoterapia/métodos , Nivolumabe/uso terapêutico , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/terapia , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Cistadenocarcinoma Seroso/diagnóstico por imagem , Seguimentos , Humanos , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Nivolumabe/farmacologia , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(29): e16433, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335697

RESUMO

RATIONALE: Endometrial neuroendocrine carcinoma is a rare histological subtype of endometrial cancer, divided into low-grade neuroendocrine carcinoma (carcinoid) and high-grade neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma). It is characterized by high invasiveness and poor prognosis. L/SCNEC is an extremely rare pathological type of endometrial carcinoma, and the number of reports on this condition is few globally. PATIENT CONCERNS: A 54-year-old Chinese female presented with vaginal bleeding. DIAGNOSES: Outpatient hysteroscopy and endometrial biopsy were performed, and the pathological examination revealed that cervix was invaded by endometrial malignancy. The patient underwent a laparoscopic radical hysterectomy was diagnosed with the mixed large and small cell neuroendocrine carcinoma (L/SCNEC) of the endometrium combined with serous carcinoma III C2 (FIGO2009). INTERVENTIONS: Chemotherapy-radiotherapy-chemotherapy "sandwich" treatment was performed as postoperative therapy. OUTCOMES: After three chemotherapy circles, the patient showed no evidence of further disease progression. LESSONS: L/SCNEC is a rare and invasive disease. Once diagnosed, comprehensive treatments including surgery, radiotherapy, and chemotherapy can prolong the survival of patients and improve the prognosis.


Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Quimioterapia Adjuvante/métodos , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Endométrio/patologia , Histerectomia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia/métodos , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/fisiopatologia , Carcinoma Neuroendócrino/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/fisiopatologia , Carcinoma de Células Pequenas/terapia , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/fisiopatologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Resultado do Tratamento , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/etiologia
20.
Obstet Gynecol ; 134(1): 17-29, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31188310

RESUMO

OBJECTIVE: To compare the outcomes of women with stage III uterine cancer treated with chemotherapy alone, external beam radiation alone, and combination chemotherapy and radiation. METHODS: The National Cancer Database was used to identify women with stage III endometrioid, serous, and clear cell uterine cancer treated with either chemotherapy (with or without vaginal brachytherapy) alone, external beam radiation (with or without brachytherapy), or combination chemotherapy and external beam radiation (with or without vaginal brachytherapy) from 2004 to 2015. Survival was estimated using Cox proportional hazards models and adjusted survival curves after propensity score analysis using inverse probability of treatment weighting to balance the clinical and demographic characteristics between the cohorts. RESULTS: Of the 20,873 patients identified, 9,456 (45.3%) received chemotherapy alone, 2,417 (11.6%) were treated with radiation alone, and 9,000 (43.1%) received chemotherapy in combination with external beam radiation. Use of combination therapy was 33.0% in 2004, and then rose to 50.5% in 2015. The mortality of the cohort was 33.1% and median survival was 115 months. Within the cohort, combination therapy was associated with a 23% reduction in mortality (hazard ratio [HR]=0.77; 95% CI 0.73-0.80) compared with chemotherapy alone. Similar findings of decreased mortality were noted in subgroup analyses for both stage IIIA (HR=0.81; 95% CI 0.68-0.98) and stage IIIC (HR=0.79; 95% CI 0.75-0.84) tumors. Similarly, when compared with radiation alone, combination therapy was accompanied by a 19% decrease in mortality (HR=0.81; 95% CI 0.73-0.89). Combination chemoradiation was associated with decreased mortality across all of the histologic subtypes. CONCLUSION: Among women with stage III uterine cancer, combination chemotherapy and external beam radiation is associated with decreased mortality compared with chemotherapy or radiation alone.


Assuntos
Neoplasias Uterinas/terapia , Adenocarcinoma de Células Claras/etnologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/etnologia , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Quimioterapia Adjuvante , Terapia Combinada , Cistadenocarcinoma Seroso/etnologia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Bases de Dados Factuais , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Análise de Sobrevida , Estados Unidos , Neoplasias Uterinas/etnologia , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia
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