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OBJECTIVE: Uterine fibroids often require hysterectomy via a laparotomy or utilizing minimally invasive surgical (MIS) approach. Morcellation is a fragmentation of the uterus into smaller pieces. The objective of this study is to determine the incidence of malignancies found in morcellated specimens at our institution. METHODS: Women who had a minimally invasive hysterectomy, for presumptive benign uterine conditions were identified, included and reviewed. Patients were divided into two groups being either benign disease or malignancies. The continuous variables uterine weight and patient age were tested for normalcy with the Shapiro-Wilk test. The exposure of subspecialist vs general gynecology was interrogated via a Chi-Squared analysis. RESULTS: 10 cases of malignancies were identified including endometrioid endometrial carcinomas (3), uterine serous carcinoma (1), endometrial stromal sarcomas (ESS) (3), and leiomyosarcomas (LMS) (3). An overall risk of occult cancer on a morcellated specimen was .73%; leiomyosarcoma was 0.22%, endometrial stromal sarcoma 0.22%, and endometrial cancer 0.29%. The median uterine weight for the 10 morcellated malignancies was 293.5g whereas the median weight for the benign uteri was only 117.5g giving a theta of -106 (95% CI -261,20). There was no difference in patient age or surgeon type between the groups (See Table 1). CONCLUSIONS: Morcellation was associated with substantially higher risk of abdominopelvic recurrence and lower disease-free survival. Morcellated uterine malignancies were significantly heavier than benign uteri. Further research on uterine morcellation should focus on decision and cost-benefit analyses to determine the ideal candidate in whom uterine morcellation during minimally invasive hysterectomy would facilitate more good than harm.
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Leiomioma/patología , Neoplasias Uterinas/patología , Estudios de Cohortes , Femenino , Humanos , Histerectomía/métodos , Leiomioma/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Miomectomía Uterina/métodos , Neoplasias Uterinas/cirugíaRESUMEN
OBJECTIVES: Lymphadenectomy as a part of the staging for EC patients is controversial. Sentinel lymph node detection has been introduced to determine which patients would benefit from adjuvant therapy and to limit morbidities associated with a full pelvic nodal dissection. The purpose of this study is to evaluate diagnostic accuracy and detection rate of robotic sentinel lymph node detection (RSLND) as a part of the surgical staging for EC. METHODS: A retrospective database of all patients who underwent intraoperative lymphatic mapping using cervical injection methylene blue followed by RSLND as a part of their procedure was reviewed. Sentinel lymph node (SLN) was initially examined by routine Hematoxylin and Eosin (H&E) and ultrastaging by immunohistochemistry (IHC). RESULTS: Between 4/2011 and 6/2013, 120 patients with endometrial cancer underwent RSLND. The median age was 62years (25-87); median BMI was 32 (18-76). Out of 120 patients, only one patient underwent RSLND with fertility preservation; and 119 patients underwent robotic hysterectomy and surgical staging with RSLND. None of the cases was converted to an open procedure. At least 1 SLN was detected in 86% (103/120) of the patients. Bilateral SLNs were detected in 52% (62/120). Positive nodes were identified in 8% (10/120) of the patients. Of those with SLN (+), 50% (5/10) were by ultrastaging (IHC) alone. No patients had positive regional nodes without SLN (+). CONCLUSIONS: RSLND using methylene blue cervical injection can identify SLN in most patients with EC. IHC ultrastaging improves the detection of node positive disease when compared to traditional pathological evaluation.
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Adenocarcinoma de Células Claras/cirugía , Carcinoma Endometrioide/cirugía , Carcinosarcoma/cirugía , Neoplasias Endometriales/cirugía , Ganglios Linfáticos/patología , Procedimientos Quirúrgicos Robotizados/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/secundario , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/secundario , Carcinosarcoma/patología , Carcinosarcoma/secundario , Colorantes , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía , Azul de Metileno , Persona de Mediana Edad , Ovariectomía , Pelvis , Estudios Retrospectivos , SalpingectomíaRESUMEN
Retroperitoneum Mullerian neoplasms are extremely rare malignancies. We report a case of a 35-year-old woman who presented with a 12-year history of lower abdominal cystic lesion, presumed of renal origin and benign, as such was not followed for 10 years. Prior to pregnancy, the patient received additional imaging and the lesion was again redemonstrated and questioned to be of ovarian origin. As such, the patient underwent laparoscopy for planned cystectomy and was found to have normal ovaries. After pregnancy, the lesion had increased in size and surgical excision revealed that the cystic mass was retroperitoneal in origin. The histopathology was reported as microinvasive mucinous adenocarcinoma with Mullerian origin. Positron emission tomographic scanning, colonoscopy, and endoscopy were unrevealing. Tumor markers were followed and follow-up scans demonstrated no recurrence. The preoperative diagnosis of primary retroperitoneal adenocarcinomas of Mullerian origin is difficult, and a definitive diagnosis cannot be made without postsurgical histopathological analysis. However, it is important for radiologists to recognize imaging features of this entity and include it in the differential diagnosis. Here we report a case and review imaging features reported for retroperitoneal primary adenocarcinomas of Mullerian origin.
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OBJECTIVE: Controversy exists regarding optimal management of high risk localized endometrial cancer. Given that vaginal brachytherapy (VB) alone is used routinely at our institution, we retrospectively reviewed our outcomes among high risk patients defined according to the PORTEC, GOG 99, and/or Aalders randomized trials of pelvic radiation versus observation to determine if acceptable rates of locoregional control could be achieved with vaginal brachytherapy alone in this highest risk patient population. METHODS: The Roswell Park Cancer Institute hospital tumor registry was used to identify all patients with Stage I or IIA endometrial cancer treated between January 1992 and June 2006. A total of 464 patients were identified. Of 261 patients who received post-operative RT, 225 received VB alone. Of those 225, 87 met the high risk criteria as designated by PORTEC (at least 2 of the following high risk features: age>60, Grade 3, and/or myometrial invasion >or=Occurrences of the mathematical operator' (='were changed to 'OE'. Please check.-->50%), GOG 99 (any age with 3 high risk features: Grade 2-3, >66% myometrial invasion, and/or LVSI; age >or=50 with 2 high risk features; or age >or=70 with 1 high risk feature), and/or Aalders (Stage IC, Grade 3). Descriptive recurrence statistics are provided. RESULTS: Among 87 high risk patients treated with VB alone, 36, 77, and 14 were high risk per PORTEC, GOG 99, and Aalders respectively. Forty (46%) underwent pelvic lymph node dissection. With a median follow-up of 52 months, 3 (3.4%) pelvic recurrences were observed including 1 vaginal recurrence, 1 pelvic recurrence, and 1 local recurrence involving both the vagina and pelvis. All 3 local recurrences were successfully salvaged with pelvic RT+/-surgery. CONCLUSIONS: This represents one of the largest known series of high risk localized endometrial cancer treated with VB alone. The observed 3.4% locoregional recurrence compares favorably with the 5% locoregional recurrence noted among the highest risk patients receiving pelvic RT in the PORTEC, GOG 99, and Aalders randomized trials. In this single institution experience, the 3 local recurrences were salvaged. Based on these findings, we will continue to use VB alone in the adjuvant setting for patients with high risk localized endometrial cancer.
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Braquiterapia/métodos , Neoplasias Endometriales/radioterapia , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de RiesgoRESUMEN
BACKGROUND: Women with germline BRCA1 or BRCA2 mutations have a lifetime risk of ovarian cancer of up to 46%. Opportunistic salpingectomy has been advocated as a risk-reducing strategy owing to increasing recognition of tubal origin, yet evidence of efficacy in this high-risk population is limited. CASE: This is the case of a woman with a BRCA1 mutation who underwent prophylactic mastectomy and bilateral salpingectomy with ovarian retention before the age of 40 years. She did not undergo oophorectomy and subsequently developed stage IV high-grade serous ovarian cancer 4 years after her initial surgery. CONCLUSION: More research is needed to determine the role of prophylactic salpingectomy with delayed oophorectomy, optimal timing of completion oophorectomy, and the risks and benefits compared with up-front risk-reducing salpingo-oophorectomy.
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Carcinoma Epitelial de Ovario/diagnóstico , Genes BRCA1 , Neoplasias Ováricas/diagnóstico , Adulto , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/cirugía , Ensayos Clínicos como Asunto , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , Mastectomía , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Ovariectomía , Salpingectomía , Tomografía Computarizada por Rayos XRESUMEN
The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P < or = 0.02), in soft agar colony number and size (P < or = 0.05), and in anoikis resistance (P < or = 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining (P < or = 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination.
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Neoplasias Ováricas/enzimología , Neoplasias Ováricas/patología , Inhibidor Secretorio de Peptidasas Leucocitarias/metabolismo , Animales , Anoicis/fisiología , Western Blotting , Proliferación Celular , Femenino , Fibrinolisina/metabolismo , Expresión Génica , Humanos , Inmunohistoquímica , Inmunoprecipitación , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ratones , Ratones Desnudos , Progranulinas , Inhibidor Secretorio de Peptidasas Leucocitarias/genéticaRESUMEN
Cancer-embryo antigens or developmentally restricted differentiation antigens (DRDAGs), such as PLAC1 (CT92) and developmental pluripotency associated-2 (DPPA2/CT100), are expressed in pluripotent embryonic cells. They are also recognized as cancer-testis antigens (CT) which are proteins normally expressed only in the human germ line but that are also present in a significant subset of malignant tumors. These antigens may prove to be markers of 'repopulating' cells with stem cell-like characteristics and could be critical targets for immunotherapy in epithelial ovarian cancer (EOC). Our objective was to define the frequency of expression and immunogenicity of PLAC1 and DPPA2 in EOC and correlate expression with clinical outcome. One-step reverse transcriptase PCR was performed on 101 EOC samples and a panel of normal tissues. Expression of PLAC1 and DPPA2 in the EOC specimens was 21/101 (21%) and 31/101 (31%) respectively. In normal tissues, PLAC1 expression was restricted to the placenta while DPPA2 expression was restricted to the placenta and testis. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were also performed on a subset of specimens. Humoral immunity was demonstrable in 2/12 serum samples from patients whose tumors expressed DPPA2. There was no demonstrable antibody response to PLAC1 in patients with PLAC1 positive tumors. The presence of PLAC1 and DPPA2 did not have a statistically significant effect on recurrence-free and overall survival. The tissue-restricted expression of PLAC1 and DPPA2, their expression in a significant proportion of EOC patients, and their potential to represent markers of stem cells make DRDAGs attractive targets for antigen-specific immunotherapy in EOC.
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Biomarcadores de Tumor/sangre , Proteínas Nucleares/sangre , Proteínas Nucleares/genética , Neoplasias Ováricas/sangre , Neoplasias Ováricas/genética , Proteínas Gestacionales/sangre , Proteínas Gestacionales/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias , Biomarcadores de Tumor/inmunología , Proteínas de Ciclo Celular , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Nucleares/inmunología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Proteínas Gestacionales/inmunología , ARN Mensajero/genética , Tasa de Supervivencia , Factores de TranscripciónRESUMEN
OBJECTIVE: Optimal management of early-stage uterine papillary serous carcinoma (UPSC) remains controversial. We reviewed our outcomes in this patient population. METHODS: The Roswell Park Cancer Institute (RPCI) tumor registry identified all patients with Stages I and IIA UPSC treated between January 1992 and June 2006. The Fisher's exact test was used to compare recurrence rates by adjuvant therapy received. Overall survival (OS) estimates were made using the Kaplan-Meier method. RESULTS: Fifty-eight patients with Stage I or IIA UPSC underwent surgery. Thirty-four patients (59%) were surgically staged. Among 21 patients with Stage IA disease, 15 received adjuvant therapy. With a median follow-up of 44.7 months, only one recurrence was observed in a patient who received adjuvant brachytherapy. The 5-year OS was 66%. Among 37 patients with Stages IB-IIA, 30 patients received adjuvant therapy. With a median follow-up of 29 months, there were 7 recurrences. The 5-year OS was 60%. Although there were no significant differences in recurrence by adjuvant therapy received, a significant OS benefit was found in those who received radiation. There was no significant difference in OS distributions of those patients who received Carboplatin/Paclitaxel chemotherapy. CONCLUSIONS: Despite the limitations of our retrospective study, we have shown that even comprehensively staged early-stage UPSC patients are still at risk for recurrence despite adjuvant therapy received. Hence, all patients with this histologic diagnosis should be considered at high risk for recurrence and counseled appropriately regarding the risks and benefits of adjuvant therapy.
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Carcinoma Papilar/terapia , Cistadenocarcinoma Seroso/terapia , Neoplasias Uterinas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Quimioterapia Adyuvante , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Radioterapia Adyuvante , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugíaRESUMEN
Alarm anti-proteases are secreted locally in response to inflammation and have been shown to be elevated in cancers. Secretory leukocyte protease inhibitor (SLPI), an alarm anti-protease, is amplified in ovarian carcinoma and is induced and binds to and protects progranulin (prgn) in inflammation. We reported prgn is a survival protein in ovarian cancer and now hypothesize that SLPI/prgn would promote proliferation and survival. Neutralizing anti-SLPI antibody treatment of HEY-A8 and OVCAR3 ovarian cancer cells decreased cell number (P < 0.001), induced apoptosis and reduced prgn quantity. This was confirmed using SLPI small interfering RNA. Prgn and SLPI were co-immunoprecipitated and co-localized by confocal microscopy. Prgn is a substrate of the serine protease elastase and SLPI is an inhibitor of elastase. Elastase reduced prgn expression, inhibited proliferation in a dose-dependent manner (P = 0.01) and was pro-apoptotic. SLPI protected prgn from elastase-mediated degradation and restored its survival and proliferative function (P = 0.04). SLPI also reversed elastase's pro-apoptotic effects (P = 0.03), yielding recovery of S-phase fraction (P = 0.001) and increased cyclin D1. Treatment with a general serine protease inhibitor increased prgn, but did not reverse elastase-mediated prgn loss or apoptosis. These data demonstrate that inappropriate over-expression of the alarm anti-protease, SLPI, creates a pro-survival milieu for ovarian cancer.
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Proliferación Celular , Supervivencia Celular/fisiología , Neoplasias Ováricas/patología , Inhibidor Secretorio de Peptidasas Leucocitarias/fisiología , Línea Celular Tumoral , Medios de Cultivo Condicionados , Femenino , Silenciador del Gen , Humanos , Inmunoprecipitación , Microscopía Confocal , Microscopía Fluorescente , Pruebas de Neutralización , Interferencia de ARN , ARN Interferente Pequeño , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Inhibidor Secretorio de Peptidasas Leucocitarias/genética , Inhibidor Secretorio de Peptidasas Leucocitarias/inmunologíaRESUMEN
PURPOSE: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. EXPERIMENTAL DESIGN: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. RESULTS: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors, whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). CONCLUSION: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma/patología , Neoplasias Ováricas/patología , Proteínas Adaptadoras Transductoras de Señales/análisis , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Proteínas Reguladoras de la Apoptosis/análisis , Carcinoma/química , Carcinoma/metabolismo , Núcleo Celular/química , Núcleo Celular/metabolismo , Citoplasma/química , Citoplasma/metabolismo , Femenino , Proteínas HSP70 de Choque Térmico/análisis , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/química , Neoplasias Ováricas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína bcl-X/análisis , Proteína bcl-X/metabolismoRESUMEN
An abdominal mass may present with a myriad of symptoms resulting from compression of surrounding organs. A major clinical challenge with practical implications is accurate preoperative identification of the origin of the mass. Here, we present the case of a 29-year-old female patient with abdominal distension and shortness of breath for approximately 6 weeks before presentation. A large abdominal mass compressing the surrounding organs was observed on abdominal x-ray and computed tomography of the abdomen and pelvis. Preoperative imaging was unable to identify the organ of origin; pathologic and histologic analyses of the tumor ultimately identified a rare, massive intra-abdominal endometrioma, freely floating within the peritoneum and fed by an omental blood supply. This case highlights the importance of considering an atypical presentation of endometriosis in women of reproductive age with abdominal complaints.
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Ovarian cancer is the leading cause of death from gynecologic malignancies among American women and the fourth most frequent cause of death from cancer in women in Europe and the US. Despite appropriate surgical and chemotherapeutic intervention, the 5-year survival in patients with metastatic cancer remains poor. Currently available screening methods, including CA125, additional biomarkers, and transvaginal ultrasound lack the necessary sensitivity and specificity to provide accurate and cost-efficient screening for the general population or the ability to assess who will benefit most from each treatment. These limitations have prompted the study of proteomic technology and its application in ovarian cancer diagnostics. Proteomics is the study of molecules in the functional protein pathways of normal or diseased states. Clinical trials are currently being conducted to assess the sensitivity and specificity of serum proteomic patterns and additional clinical trials are designed to evaluate the effects of molecularly targeted agents on protein signaling pathways in human subjects. Overcoming both scientific and practical limitations will lead to increased knowledge of deranged protein networks in cancer cells. Clinical trials in proteomics may result in improved early detection, better monitoring, new drugs and molecularly targeted therapeutics, and individualized therapies.
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Ensayos Clínicos como Asunto/métodos , Neoplasias Ováricas/diagnóstico , Proteómica , Biomarcadores de Tumor/sangre , Femenino , Humanos , Espectrometría de Masas , Proteínas de Neoplasias/sangre , Neoplasias Ováricas/sangre , Neoplasias Ováricas/terapia , Farmacogenética , Análisis por Matrices de ProteínasRESUMEN
BACKGROUND: Hypodysfibrinogenemia is an autosomally dominant disorder that can result in excessive bleeding as well as specific pregnancy complications. Increased risks of spontaneous abortion, postpartum hemorrhage, poor wound healing, and placental abruption have been reported. CASE: A woman with hypodysfibrinogenemia presented for care in the first trimester. Her antepartum course was uncomplicated, and she was administered intermediate-purity factor VIII during labor and did not have excessive bleeding postpartum. The infant's cord fibrinogen was low, at 43 mg/dL (normal 215 +/- 30), showing it was similarly affected. CONCLUSION: Pregnancy in patients with hypodysfibrinogenemia can be associated with various complications; however, coordination of care and anticipation of specific problems can result in a successful outcome for both mother and infant.
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Trastornos de la Coagulación Sanguínea/diagnóstico , Fibrinógenos Anormales/metabolismo , Complicaciones Hematológicas del Embarazo/diagnóstico , Adulto , Afibrinogenemia/diagnóstico , Afibrinogenemia/terapia , Trastornos de la Coagulación Sanguínea/terapia , Factor VIII/administración & dosificación , Femenino , Sangre Fetal/metabolismo , Fibrinógeno/metabolismo , Humanos , Trabajo de Parto , Embarazo , Complicaciones Hematológicas del Embarazo/terapia , Resultado del EmbarazoRESUMEN
Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas >10(5) parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. (13)C-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively, we demonstrated that spheroid cells with cancer stem cell-like characteristics contributed to tumor generation, progression and chemotherapy resistance. This study provides insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells and has clinical implications for cancer therapy.
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Transformación Celular Neoplásica/metabolismo , Resistencia a Antineoplásicos , Hipoxia/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Aldehído Deshidrogenasa/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Humanos , Huésped Inmunocomprometido , Metástasis de la Neoplasia , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Esferoides Celulares , Carga Tumoral/efectos de los fármacos , Carga Tumoral/genética , Carga Tumoral/inmunología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background. HPV vaccination may prevent thousands of cases of cervical cancer. We aimed to evaluate the understanding and acceptance of the HPV vaccine among adolescents. Methods. A questionnaire was distributed to adolescents at health clinics affiliated with a large urban hospital system to determine knowledge pertaining to sexually transmitted diseases and acceptance of the HPV vaccine. Results. 223 adolescents completed the survey. 28% were male, and 70% were female. The mean age for respondents was 16 years old. Adolescents who had received the HPV vaccine were more likely to be female and to have heard of cervical cancer and Pap testing. Of the 143 adolescents who had not yet been vaccinated, only 4% believed that they were at risk of HPV infection and 52% were willing to be vaccinated. Conclusions. Surveyed adolescents demonstrated a marginal willingness to receive the HPV vaccine and a lack of awareness of personal risk for acquiring HPV.
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Differentiating uterine serous carcinoma (USC) from endometrioid adenocarcinoma (EAC) could be problematic, especially in high-grade EACs and tumors exhibiting architectural variations. To address this issue, we evaluated 103 endometrial carcinoma cases using 4 immunomarkers, beta-catenin, IMP3, PTEN, and p53. Cases included 31 USCs, 57 EACs, and 15 mixed EAC-USCs. Of 31 USCs and 57 EACs, 8 and 9, respectively, were considered diagnostically difficult and challenging. beta-catenin was more frequently expressed in EAC (P = .001); p53, PTEN, and IMP3 were more frequently found in USC (P < .001 for each). IMP3 was the best independent predictive marker for USCs. The best marker combination for predicting USCs was PTEN+/IMP3+ (exact odds ratio, 163.87; 95% confidence interval, 19.62 to infinity; P < .001). IMP3 was consistently negative in all 9 challenging EAC cases and consistently positive in all 8 challenging USC cases. None of the markers or their combinations demonstrated any value in making the diagnosis of serous component in mixed EAC-USC tumors. IMP3 immunoexpression and the IMP3+/PTEN+ pattern are the best independent and combination markers, respectively, to predict USCs. We strongly recommend using them in difficult and challenging cases.
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Biomarcadores de Tumor/análisis , Carcinoma Endometrioide/patología , Cistadenocarcinoma Seroso/patología , Fosfohidrolasa PTEN/análisis , Proteínas de Unión al ARN/análisis , Neoplasias Uterinas/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/análisis , Neoplasias Uterinas/diagnóstico , beta Catenina/análisisRESUMEN
During the past decade, significant progress has been made in understanding the interactions between the immune system and cancer. The re-emergence of cancer immunosurveillance and immunoediting concepts has provided an understanding of several immunologic markers that are associated with cancer progression and prognosis. Recent studies have attempted to define the critical role of tumor infiltration by lymphocytes as a reflection of a tumor-related immune response. More recently, there has been an improved ability to demonstrate distinct subsets of tumor-infiltrating lymphocytes (TILs) in different tumor compartments. Several of these studies indicate that the presence of TILs may be associated with improved clinical outcome in several human cancers. However, this improved clinical outcome is dependent upon the intratumoral balance and quality of TILs, or infiltration of regulatory T cells or myeloid-derived suppressor cells. Immunologic markers have an important role in demonstrating intermediate end points of a therapeutic intervention and ultimately may be useful in predicting clinical outcomes. These markers are important to the development of successful immunotherapy strategies in cancer.
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BACKGROUND: c-Kit and platelet-derived growth factor receptor (PDGFR) are potential molecular targets in epithelial ovarian cancer (EOC). Imatinib inhibits the kinase domain and subsequent downstream signaling of these receptor tyrosine kinases. The objective of this study was to investigate biochemical and biologic effects of imatinib on EOC. METHODS: Patients with recurrent EOC who had received no more than 4 prior regimens and who had good end-organ function were eligible. Imatinib was administered orally at a dose of 400 mg twice daily in continuous, 28-day cycles with reassessment imaging studies obtained every other cycle. Tumor core biopsies were obtained prior to and at 4 weeks into therapy; microdissected tumor and stroma were subjected to protein lysate array analysis. Blood samples were obtained monthly for cytokine measurements. RESULTS: Twenty-three patients were enrolled, including 16 patients who received imatinib 600 mg daily because of gastrointestinal (GI) toxicity and fluid accumulation at the starting dose. The median time to disease progression was 2 months (range, 2-14 months). Common grade 3 toxicities included edema/ascites/pleural effusions in 11 patients (48%), GI complaints in 8 patients (35%), fatigue in 3 patients (13%), and grade 2 and 3 cytopenias in 10 patients and 3 patients (43% and 13%), respectively. Increased circulating levels of interleukin 6 were associated with grade >/=2 fluid collection (P = .02). A statistically significant trend was observed between pretreatment phosphorylated-kit levels in microdissected tumor and stroma and GI toxicity (P < .01), between tumor levels of epidermal growth factor receptor (EGFR) and PDGFR with grade of fatigue (P = .005), and EGFR and phosphorylated-AKT levels with grade of ascites and edema (P = .01). CONCLUSIONS: The results of this study indicated imatinib had minimal activity as a single agent in EOC. Its ability to modulate its molecular targets suggests that it may be considered in combinatorial therapy.
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Antineoplásicos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Piperazinas/uso terapéutico , Proteoma , Proteínas Proto-Oncogénicas c-kit/metabolismo , Pirimidinas/uso terapéutico , Adulto , Antineoplásicos/efectos adversos , Ascitis , Benzamidas , Citocinas/sangre , Femenino , Humanos , Mesilato de Imatinib , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Piperazinas/efectos adversos , Estudios Prospectivos , Pirimidinas/efectos adversos , Resultado del TratamientoRESUMEN
Ovarian cancer is the leading cause of gynecologic cancer death in the Western world and more than 70% of patients are diagnosed with advanced stage disease. The high mortality rate is due to the difficulty in the early detection of ovarian cancer. Current screening strategies lack the necessary sensitivity and specificity to reliably and accurately diagnose affected women, prompting investigators to seek alternative means of analysis found in protein pathways and networks. Proteomics seeks to advance the understanding of how proteins interact in cancer and may provide a mechanism for early stage diagnosis. The proteomic techniques of laser capture microdissection, mass spectrometry and tissue lysate arrays have led to the discovery of new biomarkers and the identification, development and approval of a number of targeted therapeutic agents. Following validation through clinical trials, the application of these techniques will contribute to the changing paradigm of cancer detection and treatment toward personalized medicine.
RESUMEN
BACKGROUND: Pneumatosis intestinalis is a rare condition characterized by subserosal and submucosal gas-filled cysts in the gastrointestinal tract; it may be associated with bowel ischemia, perforation, and a high mortality rate. As a result, many authorities advocate an aggressive surgical approach in patients with pneumatosis intestinalis. CASE: A 53-year-old female with recurrent, metastatic uterine leiomyosarcoma underwent resection of the pelvic recurrence, low anterior rectal resection with primary anastomosis, and partial hepatectomy for liver metastasis. Her postoperative course was notable for a small bowel obstruction and the finding of pneumatosis intestinalis on radiologic studies. The patient developed mild abdominal pain. She did not develop tenderness or fevers. She was managed with bowel rest, nasogastric tube decompression, total parenteral nutrition, and broad-spectrum antibiotics. The finding of pneumatosis intestinalis resolved over the ensuing 6 days. Her diet was slowly advanced, and she was discharged home in stable condition without further surgical intervention or recurrence of the obstruction or pneumatosis. Currently, her only evidence of disease is pulmonary metastases. CONCLUSIONS: In select patients, the outcome of a conservative approach to the management of pneumatosis intestinalis is not much different than surgical re-exploration for highly selected patients. The clinical condition of the patient, not solely the finding of pneumatosis intestinalis, should drive management in these cases.