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1.
Int J Gynecol Cancer ; 33(9): 1331-1344, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37591609

RESUMO

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Consenso , Qualidade de Vida , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia
2.
Gynecol Oncol ; 175: 60-65, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37327540

RESUMO

OBJECTIVE: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. METHODS: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. RESULTS: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42). CONCLUSION: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Estados Unidos/epidemiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Terapia Neoadjuvante/métodos , Quimioterapia Adjuvante/métodos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/patologia , Neoplasias Peritoneais/patologia , Cistadenocarcinoma Papilar/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos
3.
Gynecol Oncol ; 174: 157-166, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37207500

RESUMO

OBJECTIVES: Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the molecular landscape is crucial for optimising targeted therapy. METHODS: Genomic data from whole exome sequencing of tumour tissue was analysed in a LGSOC cohort with detailed clinical annotation. RESULTS: 63 cases were analysed and three subgroups identified based on single nucleotide variants: canonical MAPK mutant (cMAPKm: 52%, KRAS/BRAF/NRAS), MAPK-associated gene mutation (MAPK-assoc: 27%) and MAPK wild-type (MAPKwt: 21%). NOTCH pathway disruption occurred across all subgroups. Tumour mutational burden (TMB), mutational signatures and recurrent copy number (CN) changes varied across the cohort with co-occurrence of chromosome 1p loss and 1q gain (CN Chr1pq) a recurrent feature. Low TMB and CN Chr1pq were associated with inferior disease-specific survival (HR 6.43; p < 0.001 and HR 3.29, p = 0.011 respectively). Stepwise genomic classification in relation to outcome resulted in four groups (TMB low; CN Chr1pq; MAPKwt/MAPKassoc; cMAPKm). 5 year disease-specific survival was 46%, 55%, 79% and 100% respectively for these groups. The two most favourable genomic subgroups were enriched for the SBS10b mutational signature, particularly the cMAPKm subgroup. CONCLUSIONS: LGSOC comprises multiple genomic subgroups with distinct clinical and molecular features. Chr1pq CN arm disruption and TMB represent promising methods to identify individuals with poorer prognosis. Further investigation of the molecular basis for these observations is required. MAPKwt cases represent around a fifth of patients. NOTCH inhibitors represent a candidate therapeutic strategy worthy of exploration across these cases.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Feminino , Humanos , Sequenciamento do Exoma , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Cistadenocarcinoma Seroso/patologia , Mutação , Biomarcadores Tumorais/genética , Genômica
4.
Int J Gynecol Cancer ; 33(3): 377-384, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36878564

RESUMO

Low-grade serous ovarian cancer is a rare subtype of epithelial ovarian cancer clinically characterized by younger age at diagnosis, relative chemoresistance, and prolonged survival compared with its high-grade serous counterpart. It is molecularly characterized by estrogen and progesterone receptor positivity, aberrations in the MAPK (mitogen-activated protein kinase) pathway, and wild-type TP53 expression pattern. As research into low-grade serous ovarian cancer as a distinct entity has been able to accelerate independently, we have learned more about its unique pathogenesis, oncogenic drivers, and opportunities for novel therapeutics. In the primary setting, cytoreductive surgery in combination with platinum-based chemotherapy remain the standard of care. However, low-grade serous ovarian cancer has demonstrated relative chemoresistance in the primary and recurrent settings. Endocrine therapy is also commonly utilized in the maintenance and recurrent settings and is being evaluated in the adjuvant setting. Given the many similarities of low-grade serous ovarian cancer to luminal breast cancer, many recent studies have utilized similar therapeutic strategies including endocrine therapy combinations with CDK (cyclin-dependent kinase) 4/6 inhibitors. Additionally, recent trials have investigated combination therapies targeting the MAPK pathway, including MEK (mitogen-activated protein kinase kinase), BRAF (v-raf murine sarcoma viral oncogene homolog B1), FAK (focal adhesion kinase), and PI3K (phosphatidylinositol 3-kinase) inhibition. In this review, we will outline these novel therapeutic strategies for low-grade serous ovarian cancer.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Camundongos , Animais , Feminino , Humanos , Fosfatidilinositol 3-Quinases , Carcinoma Epitelial do Ovário , Terapia Combinada , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
5.
Gynecol Oncol ; 165(3): 560-567, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35606067

RESUMO

OBJECTIVE: Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes. METHODS: The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed. RESULTS: Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS. CONCLUSIONS: Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Carcinoma Epitelial do Ovário/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Genômica , Humanos , Mutação , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia
6.
Autops. Case Rep ; 12: e2021357, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1360153

RESUMO

Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included as a separate entity in the World Health Organization (WHO) classification of salivary gland tumors and in 2017 WHO Classification, the tumor was clubbed as a sub-variant of adenocarcinoma, not otherwise specified. It most commonly occurs in the major salivary glands. Herein we report a case of salivary papillary cystadenocarcinoma in a 54-year-old female, who presented with rapid enlargement of the right parotid swelling. Based on radiology and fine-needle aspiration cytology, a working diagnosis of the malignant tumor involving the superficial lobe of the right parotid gland was made. In view of the malignant nature of the swelling, superficial parotidectomy was done. The histopathology and immunohistochemistry of the mass confirmed the diagnosis of papillary cystadenocarcinoma of the right parotid. With the revised 2017 WHO classification of salivary gland tumors, it is important to report all rare subtypes in order to understand their biology and behavior.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Parotídeas/patologia , Cistadenocarcinoma Papilar/patologia
7.
Gynecol Oncol ; 160(1): 214-218, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33393480

RESUMO

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a variant of endometrial cancer that is aggressive and associated with poor outcomes. We sought to evaluate the cost effectiveness of carboplatin/paclitaxel alone versus carboplatin/paclitaxel with trastuzumab among patients with Her2/neu-positive advanced or recurrent UPSC. METHODS: We designed a Markov model in TreeAge Pro 2019 software to simulate management of a theoretical cohort of 4000 patients with Her2/neu-positive advanced or recurrent uterine papillary serous carcinoma (UPSC) followed for four years. In the carboplatin/paclitaxel with trastuzumab strategy, we included the cost of testing for Her2/neu status. We obtained all model inputs from the literature and a societal perspective was assumed. Outcomes included progression-free survival, progression, UPSC-specific mortality, cost, and quality-adjusted life years (QALYs). The intervention was considered cost effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were used to determine the robustness of the results. RESULTS: In our theoretical cohort of 4000 women, treatment with the addition of trastuzumab resulted in 637 fewer deaths and 627 fewer cases of progression compared with treatment with carboplatin/paclitaxel alone. Treatment with trastuzumab was associated with an additional cost of $144,335,895, but was associated with an increase of 2065 QALYs. The ICER was $69,903 per QALY, which was below our willingness-to-pay threshold. Sensitivity analysis demonstrated that this treatment strategy was cost-effective until the cost of 6 months of treatment surpassed $38,505 (baseline input: $27,562). CONCLUSION: We found that the addition of trastuzumab to carboplatin/paclitaxel was a cost-effective treatment strategy for patients with advanced/recurrent Her2/neu-positive UPSC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Seroso/tratamento farmacológico , Trastuzumab/economia , Neoplasias Uterinas/tratamento farmacológico , Carboplatina/administração & dosagem , Carboplatina/economia , Análise Custo-Benefício , Cistadenocarcinoma Papilar/economia , Cistadenocarcinoma Papilar/metabolismo , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/economia , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Cadeias de Markov , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/economia , Anos de Vida Ajustados por Qualidade de Vida , Receptor ErbB-2/metabolismo , Trastuzumab/administração & dosagem , Estados Unidos , Neoplasias Uterinas/economia , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
9.
Am J Case Rep ; 21: e920487, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31929500

RESUMO

BACKGROUND Omental calcifications of the peritoneum are typically small and asymptomatic. However, larger psammomatous bodies that cause symptoms such as abdominal pain and bloating are often associated with tumors such as primary serous papillary carcinoma, mesothelioma, or metastatic ovarian cancer. CASE REPORT We describe omental calcifications in a 68-year-old woman who had been asymptomatic for the last 10 years. The case details the histomorphologic features and immunohistochemical signature of a 4.0×3.5×1.0 cm mass consisting of mature adipose tissue that was surgically removed together with an 8.5×6.5×1.8 cm irregular intra-abdominal/mesenteric mass composed of yellow-red fatty tissue. Microscopic sections contained fat with variable clustered classic/psammomatous calcifications, some with a thin epithelioid periphery, in association with a very focal and subtle papillary surface epithelial/mesothelial proliferation. Tumor cell invasion was not observed during examination. Immunohistochemical staining showed that mesothelial cells in the mass were strongly positive for calretinin and focally positive for EMA, CK903, and vimentin. Strong nuclear positivity for PAX8 was also reported. Additional stains were added in response to this pattern, showing strong positivity for CK8, moderate positivity for BAP1, focal positivity for ER, minimal positivity for CD56, and negativity for CK5/6 and D2-40. Three possible explanations are suggested for the phenomenon observed in the pathology slides: reactive mesothelial hyperplasia, well-differentiated papillary mesothelioma, or serous papillary carcinoma of the peritoneum. CONCLUSIONS Findings suggest that these calcifications are a benign, reactive phenomenon, and that the abundance of psammoma bodies may be related to ongoing crops of papillary mesothelial hyperplasia or benign well-differentiated papillary mesothelioma.


Assuntos
Calcinose , Mesotelioma/diagnóstico , Mesotelioma/patologia , Omento/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Idoso , Biomarcadores Tumorais , Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico , Imuno-Histoquímica
10.
Gynecol Oncol ; 156(1): 77-84, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31796203

RESUMO

OBJECTIVE: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC). PATIENTS AND METHODS: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm. RESULTS: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29). CONCLUSION: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC.


Assuntos
Algoritmos , Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Seroso/tratamento farmacológico , Aprendizado de Máquina , Neoplasias Uterinas/tratamento farmacológico , Idoso , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/cirurgia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
11.
Tokai J Exp Clin Med ; 44(3): 49-53, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31448396

RESUMO

BACKGROUND: Peritoneal serous papillary carcinoma (PSPC) is a rare disease. It is clinically and histologically similar to progressive ovarian serous adenocarcinoma and involves normal-sized ovaries, making it challenging to diagnose. In this report, we describe a case of peritoneal serous papillary carcinoma that was difficult to identify and how we made a correct diagnosis in order to begin a timely course of treatment. CASE PRESENTATION: A 63-year-old woman with chief complaints of dizziness and abdominal pain was examined, but showed no particular abnormality. Class III cytology of the endometrium was detected through magnetic resonance imaging and a laparotomy was performed on suspicion of endometrial cancer. The patient was finally diagnosed with peritoneal serous papillary carcinoma and was treated with surgical resection and the standard indicated course of chemotherapy. CONCLUSIONS: The diagnosis and treatment of peritoneal serous papillary carcinoma may be delayed or may not be performed unless Class III findings are detected through uterine mucosal cytology before surgery. Surgeons should not hesitate to perform laparotomy when necessary to identify and appropriately treat patients, even if abnormalities are not detected in the preoperative examination.


Assuntos
Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Neoplasias Peritoneais/diagnóstico , Quimioterapia Adjuvante , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/cirurgia , Cistadenocarcinoma Seroso/cirurgia , Citodiagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Laparotomia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Ovarianas , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia
12.
J Gynecol Oncol ; 30(3): e44, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887761

RESUMO

OBJECTIVE: To compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC). METHODS: Medical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups. RESULTS: Fifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1±20.2 vs. 11.5±6.5 IU/mL, p<0.001), open surgery (71.2% vs. 28.6%, p=0.001), myometrial invasion (MI) ≥1/2 (33.9% vs. 0, p=0.002), and lymphovascular space invasion (LVSI; 28.8% vs. 4.8%, p=0.023) were frequent in women who received adjuvant therapy compared to those who did not. However, the histologic type, MI ≥1/2, and LVSI did not differ between women who received adjuvant radiotherapy and those who received chemotherapy. The 5-year progression-free survival (78.9% vs. 80.1%, p>0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297-11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288-9.321; p=0.578) after surgery was independently associated with disease recurrence. CONCLUSION: Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.


Assuntos
Adenocarcinoma de Células Claras , Quimioterapia Adjuvante/mortalidade , Cistadenocarcinoma , Neoplasias do Endométrio , Radioterapia Adjuvante/mortalidade , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/mortalidade , Cistadenocarcinoma/mortalidade , Cistadenocarcinoma/patologia , Cistadenocarcinoma/terapia , Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/terapia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Histerectomia/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , República da Coreia/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Int J Gynecol Cancer ; 28(7): 1311-1317, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29958235

RESUMO

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a highly aggressive subtype of endometrial carcinoma. Histopathologically, it resembles the pattern of serous papillary carcinoma of the ovary. Cancer antigen 125 (CA-125) is the most widely used biomarker in epithelial ovarian carcinoma. Its use in UPSC evaluation has yet to be determined. The purpose of this study was to investigate the significance of preoperative serum CA-125 as a prognostic factor in patients with UPSC. METHODS: The study cohort included all women with UPSC operated in our institution between January 2002 and June 2016. All patients underwent complete surgical staging. Preoperative CA-125 was reviewed and correlated with clinical and pathological parameters. RESULTS: Sixty-one women met the study criteria. Median preoperative CA-125 was found to be significantly associated with disease stage. Patients with disease stages I to IV had median preoperative CA-125 levels of 12.15, 19.6, 22.6, and 177.5 U/mL (P < 0.0001) respectively. Levels of CA-125 were significantly associated with positive cytology (P < 0.0001), omental disease (P < 0.0001), pelvic or para-aortic lymph node metastasis (P < 0.0001), and adnexal involvement (P < 0.0001). The optimal cutoff that provided the best sensitivity and specificity for omental and parametrial involvement as well as positive cytology was 57.5 U/mL. For adnexal and lymph node involvement, the optimal cutoff value was 41.8 U/mL. CONCLUSIONS: In patients with UPSC, preoperative CA-125 level correlates with known prognostic parameters of endometrial carcinoma and is associated with extrauterine involvement. These data should stimulate the need for further evaluation of the role of CA-125 in predicting recurrence and survival in UPSC.


Assuntos
Antígeno Ca-125/sangue , Cistadenocarcinoma Papilar/sangue , Cistadenocarcinoma Seroso/sangue , Neoplasias Uterinas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Neoplasias Uterinas/patologia
14.
Am J Case Rep ; 19: 534-539, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29731507

RESUMO

BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.


Assuntos
Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/patologia , Tubas Uterinas/patologia , Neoplasias dos Genitais Femininos/patologia , Adulto , Cistadenocarcinoma Papilar/terapia , Cistadenocarcinoma Seroso/terapia , Tubas Uterinas/cirurgia , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Hemorragia Uterina/etiologia
15.
Tumour Biol ; 40(5): 1010428318773652, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29745297

RESUMO

SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated in ovarian cancer cells by real time PCR and Western blot. SPAG9 involvement in cell cycle, DNA damage, apoptosis, paclitaxel sensitivity and epithelial- mesenchymal transition (EMT) was investigated employing RNA interference approach. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro. Quantitative PCR and Western blot analysis revealed SPAG9 expression in A10, SKOV-3 and Caov3 compared to normal ovarian epithelial cells. SPAG9 ablation resulted in reduced cellular proliferation, colony forming ability and enhanced cytotoxicity of chemotherapeutic agent paclitaxel. Effect of ablation of SPAG9 on cell cycle revealed S phase arrest and showed decreased expression of CDK1, CDK2, CDK4, CDK6, cyclin B1, cyclin D1, cyclin E and increased expression of tumor suppressor p21. Ablation of SPAG9 also resulted in increased apoptosis with increased expression of various pro- apoptotic molecules including BAD, BID, PUMA, caspase 3, caspase 7, caspase 8 and cytochrome C. Decreased expression of mesenchymal markers and increased expression of epithelial markers was found in SPAG9 ablated cells. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro assays which showed that ablation of SPAG9 resulted in increased paclitaxel sensitivity and caused enhanced cell death. In vivo ovarian cancer xenograft studies showed that ablation of SPAG9 resulted in significant reduction in tumor growth. Present study revealed therapeutic potential of SPAG9 in ovarian cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Adenocarcinoma/tratamento farmacológico , Vetores Genéticos/uso terapêutico , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Interferência de RNA , RNA Interferente Pequeno/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma Papilar/tratamento farmacológico , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos/administração & dosagem , Humanos , Injeções Intralesionais , Camundongos Nus , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Clin J Gastroenterol ; 10(6): 530-534, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28913716

RESUMO

We report a case of a mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB) diagnosed over a period of 6 years. A 64-year-old man underwent follow-up evaluations for an abdominal aortic aneurysm at our hospital. In 2009, a computed tomography (CT) scan revealed a simple hepatic cyst in segment 3 of the liver. Annual CT scans initially showed almost no change in the size or shape of the cyst. The cystic lesion, which measured 5 cm in 2014, had increased to 11 cm by 2015, and a solid component was detected within the cyst. A biliary cystic tumor was suspected and we performed a left lateral hepatectomy. Pathological examination showed that the papillary lesion in the cyst included adenocarcinoma and adenoma components. We diagnosed M-IPNB in 2015. Identification of the solid component of the cyst, as well as an increase in cyst diameter in the image analyses, was critical for diagnosis of M-IPNB.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Papilar/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/cirurgia , Cistadenocarcinoma Mucinoso/diagnóstico por imagem , Cistadenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Papilar/diagnóstico por imagem , Cistadenocarcinoma Papilar/cirurgia , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
18.
Int J Gynecol Cancer ; 27(4): 720-729, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28375927

RESUMO

OBJECTIVE: The aim of the study was to assess interaction of lymph node dissection (LND), adjuvant chemotherapy (CT), and radiotherapy (RT) in stage I uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCC). METHODS/MATERIALS: The National Cancer Data Base was queried for women diagnosed with International Federation of Gynecology and Obstetrics stage I UPSC and UCC from 1998 to 2012. Overall survival (OS) was estimated for combinations of RT and CT by the Kaplan-Meier method stratified by histology and LND. Multivariate Cox proportional hazard models were generated. RESULTS: Uterine papillary serous carcinoma: 5432 women with UPSC were identified. Uterine papillary serous carcinoma had the highest 5-year OS with CT + RT with (83%) or without LND (76%). On multivariate analyses, CT [hazard ratio (HR), 0.77; P = 0.01] and vaginal cuff brachytherapy (HR, 0.68; P = 0.003) with LND were independently associated with OS. Without LND, vaginal cuff brachytherapy (HR, 0.53; P = 0.03), but not CT (HR, 1.21; P = 0.92), was associated with OS. Uterine clear cell carcinoma: 2516 women with UCC were identified. Uterine clear cell carcinoma with and without LND had comparable 5-year OS for all combinations of CT and RT on univariate and multivariate analyses. CONCLUSIONS: In stage I papillary serous uterine cancer, brachytherapy and CT were associated with increased survival; however, the benefit of chemotherapy was limited to those with surgical staging. In contrast, no adjuvant therapy was associated with survival in stage I uterine clear cell carcinoma, and further investigation to identify more effective therapies is warranted.


Assuntos
Adenocarcinoma de Células Claras/terapia , Cistadenocarcinoma Papilar/terapia , Cistadenocarcinoma Seroso/terapia , Neoplasias Uterinas/terapia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Carboplatina/administração & dosagem , Quimiorradioterapia , Quimioterapia Adjuvante , Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estados Unidos/epidemiologia , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia
19.
J Ovarian Res ; 10(1): 28, 2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28427435

RESUMO

BACKGROUND: Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-ß has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-ß and LH in ovarian cancer. METHODS: The study was conducted on 60 patients with ovarian tumors (benign, borderline and malignant) and 20 healthy volunteers. LH and TGF-ß serum levels were measured by ELISA. Expression of prohibitin and LHR-mRNA were assessed by IHC and TaqMan® real time gene expression assay, respectively. RESULTS: Serum levels of LH and TGF-ß were significantly decreased among borderline and malignant groups. There was significant over-expression of LHRmRNA in malignant group. Prohibitin expression was significantly increased in malignant ovarian tissue. Strong negative correlations were found between LHR mRNA expression and serum LH levels, and between IHC score of prohibitin and serum levels of LH among patients with borderline ovarian tumors. CONCLUSION: Steady decline of LH and TGF-B serum levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their inhibitory role against OET cell growth. Increased PHB1 expression in OET suggests its proliferative activity that can be regulated by luteinisation and/or TGF-ß. Furthermore increased LHR mRNA tissue expression can provide hope for using LH in treatment of some types of ovarian cancers.


Assuntos
Luteinização/fisiologia , Neoplasias Ovarianas/metabolismo , Proteínas Repressoras/biossíntese , Fator de Crescimento Transformador beta/sangue , Adulto , Cistadenocarcinoma Papilar/metabolismo , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Cistadenoma Mucinoso/metabolismo , Cistadenoma Mucinoso/patologia , Cistadenoma Papilar/metabolismo , Cistadenoma Papilar/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiologia , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Proibitinas , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptores do LH/biossíntese , Receptores do LH/genética , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia
20.
Int J Mol Sci ; 18(4)2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28398226

RESUMO

Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFß1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.


Assuntos
Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Seroso/tratamento farmacológico , Melatonina/farmacologia , Neovascularização Patológica/prevenção & controle , Neoplasias Ovarianas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Western Blotting , Cistadenocarcinoma Papilar/irrigação sanguínea , Cistadenocarcinoma Papilar/metabolismo , Cistadenocarcinoma Seroso/irrigação sanguínea , Cistadenocarcinoma Seroso/metabolismo , Etanol/administração & dosagem , Feminino , Preferências Alimentares , Imuno-Histoquímica , Injeções Intraperitoneais , Melatonina/administração & dosagem , Microscopia de Fluorescência , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/metabolismo , Ratos , Receptor MT1 de Melatonina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
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