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This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two-hundred and ninety-eight Korean women diagnosed with high-grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P < .001), indicating it is an independent prognostic factor for survival regardless of platinum sensitivity to first-line chemotherapy. In addition, a higher response rate to subsequent chemotherapy after recurrence was observed in EOC patients with BRCA mutations resulting in better OS. In the current study, the prevalence of BRCA mutations in Korean patients with EOC was higher than previously reported in other ethnic groups. We demonstrated characteristics and treatment response in Korean EOC patients with BRCA mutations. These findings may provide valuable information to be considered in future clinical trials including Asian patients.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial de Ovario/terapia , Mutación , Neoplasias Ováricas/terapia , Adulto , Anciano , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Femenino , Mutación de Línea Germinal , Humanos , Persona de Mediana Edad , Tasa de Mutación , Clasificación del Tumor , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Prevalencia , República de Corea/epidemiología , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine whether opportunistic salpingectomy in patients undergoing laparoscopic myomectomy has any deleterious effects on ovarian reserve and surgical risk. STUDY DESIGN: We performed a retrospective review of patients who had no desire for future child bearing and who were undergoing laparoscopic myomectomy for symptomatic myomas at 4 institutions. Among them, 41 patients concurrently underwent opportunistic salpingectomy (the opportunistic salpingectomy group) and 65 patients did not undergo salpingectomy at the time of laparoscopic myomectomy (the no-salpingectomy group). The primary and secondary outcome measures were change of ovarian reserve determined by the rate of decline in the anti-Müllerian hormone (AMH) level from before surgery to 3 months post-surgery, and surgical outcomes. RESULTS: Baseline characteristics were similar between groups. There were also no differences in surgical outcomes, such as operative time, operative bleeding, hospital stay, or complications between groups. The decline rate in AMH was 18.6% (interquartile range (IQR) 2.6-46.8%) in the opportunistic salpingectomy group and 10.4% (IQR 2.6-46.8%) in the no-salpingectomy group, with no significant difference between groups (p = 0.593). CONCLUSION: Opportunistic salpingectomy at the time of laparoscopic myomectomy was not associated with negative effects on ovarian reserve or increased surgical risk.
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Laparoscopía/métodos , Reserva Ovárica , Salpingectomía/efectos adversos , Miomectomía Uterina/métodos , Adulto , Hormona Antimülleriana/sangre , Femenino , Humanos , Neoplasias Ováricas/prevención & control , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the relationship between functional tumour parameters measured during preoperative 18F-FDG PET/CT and clinical outcomes in patients with uterine carcinosarcoma. METHODS: For patients with pathologically proven uterine carcinosarcoma, we determined the maximal and average standardized uptake values, cumulative total lesion glycolysis (TLG) and sum of all metabolic tumour volumes (MTVs). Their predictive value for recurrence and the effects of pretreatment functional tumour activity on patient survival were compared. RESULTS: Clinicopathological data from 28 eligible patients were reviewed. The median duration of progression-free survival was 18.6 months (range 6.1-84.5 months), and 10 (35.7 %) patients experienced recurrences. Univariate analyses showed significant associations between recurrence and tumour size, lymph node metastasis, high TLG and MTV values, and ovarian invasion. Multivariate analysis identified high TLG value as an independent risk factor for recurrence (p = 0.048, hazard ratio 115.261, 95 % confidence interval 1.041-12,765.483). Kaplan-Meier survival curves showed that progression-free survival significantly differed in groups categorized according to TLG (p = 0.007, log-rank test). CONCLUSIONS: Preoperative TLG measured with 18F-FDG PET/CT was statistically significantly associated with uterine carcinosarcoma recurrence. Metabolic parameters can provide useful quantitative criteria for disease prognostication in patients with uterine carcinosarcoma before treatment. KEY POINTS: ⢠Preoperative TLG was an independent risk factor for recurrence in uterine carcinosarcoma. ⢠Progression-free survival significantly differed in groups categorized by TLG. ⢠Metabolic parameters can provide useful quantitative criteria for disease prognostication.
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Carcinosarcoma/mortalidad , Fluorodesoxiglucosa F18/farmacocinética , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Neoplasias Uterinas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinosarcoma/diagnóstico por imagen , Carcinosarcoma/metabolismo , Supervivencia sin Enfermedad , Femenino , Glucólisis/fisiología , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Imagen Multimodal , Recurrencia Local de Neoplasia/mortalidad , Cuidados Preoperatorios , Pronóstico , Estudios Retrospectivos , Carga Tumoral , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/metabolismoRESUMEN
Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the substantia nigra and it is known to involve the accumulation of α-synuclein (α-syn), which is a neuroprotein that promotes degeneration of dopaminergic neurons. Serum/glucocorticoid-related kinase 1 (SGK1) is involved in the physiological and pathological processes in neurons. The aim of this study was to examine the relationship between SGK1 and α-syn expression in muscle tissue of a PD model and in C2C12 cells. Western blotting, immunohistochemistry, and immunofluorescence microscopy confirmed reduced SGK1 and increased α-syn expression in skeletal muscle of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared to the control group. To determine the relationship between SGK1 and α-syn, SGK1 small interfering RNA (siRNA) knockdown was performed in C2C12 cells, which showed that suppression of SGK1 levels resulted in increased α-syn expression. The main finding of our study is that reduction of SGK1 expression contributes to the pathogenesis of PD by increasing the expression of α-syn in skeletal muscle of MPTP-treated mice and C2C12 cells. This study confirms that decreased SGK1 induces increased α-syn expression in skeletal muscle, which suggests that maintaining SGK1 expression may improve PD symptoms.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Ratones , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , alfa-Sinucleína/metabolismo , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Glucocorticoides/metabolismo , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismoAsunto(s)
Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/cirugía , Escisión del Ganglio Linfático/instrumentación , Ganglios Linfáticos/patología , Dispositivos de Cierre Vascular , Aorta , Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Histeroscopía/instrumentación , Histeroscopía/métodos , Laparoscopía/instrumentación , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Persona de Mediana Edad , Tempo Operativo , Ovariectomía/métodos , Pelvis , Salpingectomía/métodosRESUMEN
Mature cystic teratoma (MCT) is the most common ovarian tumor. Secondary malignant tumors rarely arise in MCTs, and squamous cell carcinoma (SCC) is the most common form of such tumors. MCT-derived SCC in situ (CIS) is mostly found together with invasive SCC; it is seldom detected alone. A 44-year-old woman with breast cancer was found to have a left ovarian cyst (size >8 cm) before treatment. She underwent bilateral salpingo-oophorectomy, and frozen biopsy showed MCT with focal proliferation of squamous epithelium and mild atypism. However, definitive pathologic diagnosis confirmed CIS arising in MCT. In addition, germline BRCA 1/2 test and human papillomavirus test of tumor tissue yielded negative results. This report is the first case of its kind in Korea. Our report can aid in clinical decision making and serve as a basis for follow-up studies on this rare type of CIS arising in MCT.
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OBJECTIVE: To determine the optimal timing of adjuvant chemotherapy after primary cytoreductive surgery for advanced epithelial ovarian cancer. METHODS: In a retrospective cohort analysis, data were assessed from women with advanced epithelial ovarian carcinoma treated at Princess Margaret Cancer Centre, Toronto, Canada between 2002 and 2012, and at Samsung Medical Centre, Seoul, Korea, between 2002 and 2015. The treatment interval was defined as the time period between primary cytoreductive surgery and the first cycle of adjuvant chemotherapy. RESULTS: Overall, 711 women met the inclusion criteria. Among them, 247 (34.7%) had optimal cytoreduction (residual 1-9 mm), 229 (32.2%) had microscopic residual disease (0 mm), and 235 (33.1%) had suboptimal cytoreduction (≥10 mm). The median time of treatment interval was 10 days (range 3-86 days). In the optimal (1-9 mm) group, a longer treatment interval was significantly associated with poor overall survival (hazard ratio 1.02, 95% confidence interval 1.01-1.03; P=0.001) in multivariate analysis. Treatment interval was not associated with a significant difference in overall survival in the microscopic or suboptimal residual disease groups. CONCLUSION: Overall survival might be negatively affected by longer treatment intervals among women with advanced epithelial ovarian carcinoma.
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Antineoplásicos/administración & dosificación , Carcinoma Epitelial de Ovario/terapia , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Neoplasia Residual , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. MATERIALS AND METHODS: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. RESULTS: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023). CONCLUSION: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.
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Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Adulto , Animales , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor , Biopsia , Carboplatino/farmacología , Carcinoma Epitelial de Ovario , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Femenino , Inestabilidad Genómica , Xenoinjertos , Humanos , Ratones , Persona de Mediana Edad , Terapia Molecular Dirigida , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Paclitaxel/farmacología , Investigación Biomédica Traslacional , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. METHODS: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. RESULTS: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. CONCLUSION: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.
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Preservación de la Fertilidad , Recurrencia Local de Neoplasia/terapia , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Tratamientos Conservadores del Órgano , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario , Femenino , Humanos , Laparoscopía , Nacimiento Vivo , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Nacimiento a Término , Resultado del Tratamiento , Adulto JovenRESUMEN
Nongestational ovarian choriocarcinoma is an exceedingly rare and highly aggressive tumor. Although early diagnosis and timely initiation of therapy is important, it is difficult in reproductive aged patients because of the frequent elevation of human chorionic gonadotropin. We report a primarily nongestational ovarian choriocarcinoma in a 12-year-old virgin female. Initial diagnosis based on abdominopelvic computed tomography and pelvis magnetic resonance imaging was ectopic pregnancy with hemoperitoneum. A diagnostic laparoscopy of the ovarian tumor revealed choriocarcinoma. Unilateral salpingo-oophorectomy and omental sampling revealed surgical stage of IA. Six courses of adjuvant combination chemotherapy (bleomycin, etoposide, and cisplatin) followed surgery.
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Lynch syndrome is a genetic malignancy syndrome affecting the colon, endometrium, and other organs. It is difficult to find a Lynch syndrome patient without any family history of cancer. We have recently examined an endometrial cancer patient with a MSH2 gene mutation without a family history of cancer. A 55-year old Korean woman was admitted to a local clinic for vaginal bleeding. An endometrial biopsy revealed the presence of adenocarcinoma (endometrioid type, grade 1). After surgical staging, no further adjuvant therapy was required. Analysis of the tissue using immunohistochemistry (IHC) showed the endometrium stained negatively for MSH2. Microsatellite instability (MSI) was analyzed for five markers. The patient was scored as unstable. Further, additional gene sequencing revealed one missense mutation in c.23C > T (p.Thr8Met). This is the first case of Lynch syndrome endometrial cancer in Korea in which the patient does not have any family history of cancer.