RESUMEN
Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.
Asunto(s)
Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/metabolismo , Animales , Antígenos CD/análisis , Antígenos CD/genética , Antígenos de Neoplasias , Carboplatino/farmacología , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral/efectos de los fármacos , Movimiento Celular , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Estimación de Kaplan-Meier , Ratones Endogámicos NOD , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Many cancers are dependent on inappropriate activation of epidermal growth factor receptor (EGFR), and drugs targeting this receptor can improve patient survival, although benefits are generally short-lived. We reveal a novel mechanism linking EGFR and the membrane-spanning, cancer-promoting protein CDCP1 (CUB domain-containing protein 1). Under basal conditions, cell surface CDCP1 constitutively internalizes and undergoes palmitoylation-dependent degradation by a mechanism in which it is palmitoylated in at least one of its four cytoplasmic cysteines. This mechanism is functional in vivo as CDCP1 is elevated and palmitoylated in high-grade serous ovarian tumors. Interestingly, activation of the EGFR system with EGF inhibits proteasome-mediated, palmitoylation-dependent degradation of CDCP1, promoting recycling of CDCP1 to the cell surface where it is available to mediate its procancer effects. We also show that mechanisms inducing relocalization of CDCP1 to the cell surface, including disruption of its palmitoylation and EGF treatment, promote cell migration. Our data provide the first evidence that the EGFR system can function to increase the lifespan of a protein and also promote its recycling to the cell surface. This information may be useful for understanding mechanisms of resistance to EGFR therapies and assist in the design of treatments for EGFR-dependent cancers.
Asunto(s)
Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Receptores ErbB/metabolismo , Lipoilación , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Antígenos de Neoplasias , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/inmunología , Línea Celular Tumoral , Membrana Celular/metabolismo , Movimiento Celular , Activación Enzimática , Femenino , Humanos , Interleucina-6/farmacología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/inmunología , Trasplante de Neoplasias , Neoplasias Ováricas/patología , Transporte de Proteínas , Trasplante Heterólogo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
OBJECTIVE: Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis. METHODS: This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 µg 1.30 and 1.43, respectively) and smokers (HRs per 100 µg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 µg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98). CONCLUSIONS: Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation.
Asunto(s)
Dieta/estadística & datos numéricos , Ácido Fólico/administración & dosificación , Micronutrientes/administración & dosificación , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/mortalidad , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Australia/epidemiología , Carcinoma Epitelial de Ovario , Estudios de Casos y Controles , Estudios de Cohortes , Neoplasias de las Trompas Uterinas/genética , Neoplasias de las Trompas Uterinas/metabolismo , Neoplasias de las Trompas Uterinas/mortalidad , Neoplasias de las Trompas Uterinas/patología , Femenino , Ácido Fólico/metabolismo , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Polimorfismo de Nucleótido Simple , Fumar/epidemiología , Encuestas y CuestionariosRESUMEN
To develop a vulvar cancer-specific quality of life (QOL) subscale to accompany the Functional Assessment of Cancer-General (FACT-G) questionnaire, semistructured interviews were performed with 15 patients treated for vulvar cancer (FIGO stage 0-3). All but one patient, who received chemoradiotherapy, were treated by radical vulvectomy and six patients received a groin lymph node dissection. Patients experienced reductions in several aspects of QOL including emotional functioning, physical functioning, social functioning, sexuality, and body image. Six patients suffered from lymphedema of the legs with a mean severity of 3.5 on a 10-point scale. Four patients reported pruritus (severity rating 8.5). Seven patients expressed a need for more information about the illness and treatment. Only four patients returned to employment after treatment, and all of these patients reported work-related problems. Reductions in sexual functioning were a major concern for five patients, all younger than 65 years. Other topics were groin discomfort after removal of the lymph nodes and disturbance by odor from the vulva. Results of this study revealed vulvar cancer-specific reductions in QOL for inclusion in the newly developed vulvar cancer-specific subscale.
Asunto(s)
Calidad de Vida , Neoplasias de la Vulva/psicología , Factores de Edad , Anciano , Anciano de 80 o más Años , Imagen Corporal , Emociones , Empleo , Femenino , Humanos , Persona de Mediana Edad , Dolor , Educación del Paciente como Asunto , Estudios Prospectivos , Psicometría , Sexualidad , Apoyo Social , Neoplasias de la Vulva/tratamiento farmacológico , Neoplasias de la Vulva/radioterapia , Neoplasias de la Vulva/cirugíaRESUMEN
OBJECTIVES: The aims of this study were to assess outcomes and define prognostic factors for early-stage vaginal carcinoma. METHODS: A retrospective analysis was performed of women with FIGO stages I and II vaginal carcinoma identified from the database of the Queensland Centre for Gynaecological Cancer between January 1982 and December 1998. RESULTS: Seventy women were identified. The 5-year survivals for stages I and II carcinomas were 71 and 48%, respectively (P < 0.05). Sixty-one patients (87%) had squamous cell carcinomas with a 5-year survival of 68% versus 22% for adenocarcinomas (P < 0.01). Those women with grade 3 tumors had a 5-year survival of 40% versus 69% for grades 1 and 2 (P < 0.05). Tumor size and site were not significant prognostic factors. Patients treated by surgery alone or with combined surgery and radiotherapy had a significantly improved survival compared to the radiation alone group (P < 0.01). Eighty-five percent of recurrences were locoregional. The median time to relapse was 12 months after initiation of therapy. CONCLUSION: Tumor morphology, grade, and stage are important prognostic indicators. Measures aimed at improving local control of the disease, including surgery, are necessary.
Asunto(s)
Recurrencia Local de Neoplasia/mortalidad , Neoplasias Vaginales/mortalidad , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Registros Médicos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Queensland/epidemiología , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias Vaginales/patología , Neoplasias Vaginales/radioterapia , Neoplasias Vaginales/cirugíaRESUMEN
To determine the impact of anemia before and during chemoradiation in patients with cervical cancer, we collected data on hemoglobin (Hb) levels before and during treatment from 60 unselected patients with cervical carcinoma. All patients had FIGO stage IB to IVA disease and were treated with concurrent chemoradiation for the aim of cure. Patients with an Hb value below or equal to the lower 25th quartile were considered anemic. Progression-free survival (PFS) was evaluated by univariate and multivariate analyses. After a median follow-up of 26.3 months, 20 patients developed disease progression. The lowest Hb during chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were correlated significantly with PFS. On multivariate analysis, the nadir Hb (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1% for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly predictive of shortened PFS, whereas the Hb before treatment is prognostically not significant.
Asunto(s)
Anemia/mortalidad , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/complicaciones , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anemia/complicaciones , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Hemoglobinas , Humanos , Registros Médicos , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Queensland/epidemiología , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: The MUC1 antigen can be used to identify epithelial cells from the background of hemopoietic cells. The present investigation describes patterns of overexpression of two novel MUC1 splice variants in human cervical carcinoma cell lines. METHODS: RT-PCR was carried out to determine MUC1 splice variants in the cervical cancer cell lines C-4 II, C-33A, DoTc 2 4510, C-4 I, SiHa, HT3, Hs 636 T (C4-I), and HeLa. RESULTS: The novel MUC1 splice variant D was expressed in all cell lines and the novel MUC1 splice variant C was expressed in all cell lines but C-33A. Variants A and B were expressed in all (variant A) and all but one (variant B) cell line. MUC1/REP was expressed in all cell lines and MUC1/SEC was positive in all but two cell lines (C-33 A, DoTc 2 4510). All but one cell line (C-33A) expressed MUC1/X and MUC1/Y, and two cell lines (C-33 A, DoTc 2 4510) did not express MUC1/Z, respectively. MUC1 variants A, D, and REP could be demonstrated consistently among all eight cervical carcinoma cell lines we have examined. CONCLUSIONS: The present study describes the feasibility of detecting a large number of MUC1 variants, including MUC1 variants C and D which are described for cervical carcinoma cells for the first time. Further studies will examine the presence of MUC1 splice variants' expression in human cervical carcinoma tissue.
Asunto(s)
Empalme Alternativo , Mucina-1/genética , Neoplasias del Cuello Uterino/genética , Secuencia de Bases , Femenino , Células HeLa , Humanos , Datos de Secuencia Molecular , Mucina-1/biosíntesis , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/metabolismoRESUMEN
OBJECTIVE: To examine the feasibility and safety of a low anterior resection of the rectosigmoid plus adjacent pelvic tumour as part of primary cytoreduction for ovarian cancer. METHODS: This study included 65 consecutive patients with primary ovarian cancer who had debulking surgery from 1996 through 2000. All patients underwent an en bloc resection of ovarian cancer and a rectosigmoid resection followed by an end-to-end anastomosis. Parameters for safety and efficacy were considered as primary statistical endpoints for the aim of this analysis. RESULTS: Postoperative residual tumour was nil, <1 cm, and >1 cm in 14, 34, and 14 patients, respectively. The median postoperative hospital stay was 11 days (range, 6 to 50 days). Intraoperative complications included an injury to the urinary bladder in one patient. Postoperative complications included wound complications (n = 14, 21.5%), septicemia (n = 9, 13.8%), cardiac complications (n = 7, 10.8%), thromboembolic complications (n = 5, 7.7%), ileus (n = 2, 3.1%), anastomotic leak (n = 2, 3.1%), and fistula (n = 1, 1.5%). Reasons for a reoperation during the same admission included repair of an anastomotic leak (n = 1), postoperative hemorrhage (n = 1), and wound debridement (n = 1). Wound complications, septicemia, and anastomotic leak formation were more frequent in patients who had a serum albumin level of < or =30 g/L preoperatively. There was one surgically related mortality in a patient who died from a cerebral vascular accident 2 days postoperatively. CONCLUSIONS: An en bloc resection as part of primary cytoreductive surgery for ovarian cancer is effective and its morbidity is acceptably low.
Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Neoplasias Ováricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Colostomía/efectos adversos , Colostomía/métodos , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Persona de Mediana Edad , Recto/cirugíaRESUMEN
BACKGROUND: In patients undergoing radiation for cervical carcinoma, there is evidence that anemia is associated with an impaired outcome. For patients undergoing chemoradiation, there are no data available. The objective of this retrospective study was to examine the impact of anemia before and during chemoradiation in patients with cervical carcinoma. METHODS: The authors collected data on hemoglobin (Hb) levels before and during treatment from 57 patients with cervical carcinoma. The stage of disease ranged between Stage IB and Stage IVA. All patients were treated with concurrent chemoradiation. Response to chemoradiation was evaluated by univariate and multivariate analyses. RESULTS: The mean Hb level at the time of presentation was 12.9 +/- 1.6 g/dL in patients with a complete clinical response (CCR) and 12.1 +/- 1.4 g/dL in those with persistent disease (P = 0.126). In patients with a CCR, the mean nadir Hb level was 11.1 +/- 1.3 g/dL, and in patients with treatment failure, it was 9.8 +/- 1.8 g/dL (P = 0.008). A univariate logistic regression model demonstrated that the nadir Hb level was the most predictive factor for treatment failure (relative risk, 1.92; P = 0.015) followed by disease stage (relative risk, 0.51; P = 0.074). In a multivariate model, the nadir Hb level remained the only prognostically relevant factor predicting the response to chemoradiation. Only patients with nadir Hb values > 11 g/dL throughout chemoradiation had a more than 90% chance of achieving a CCR. CONCLUSIONS: In patients undergoing chemoradiation for cervical carcinoma, the nadir Hb level is highly predictive of response to treatment, whereas the Hb level at the time of presentation is prognostically not significant.
Asunto(s)
Hemoglobinas/metabolismo , Neoplasias del Cuello Uterino , Adulto , Anciano , Anemia/complicaciones , Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
OBJECTIVE: The aim of this study is to look at the efficacy of extended surgical staging and postoperative vaginal vault brachytherapy in patients with Stage II (occult) endometrial carcinoma. METHODS: Between January 1989 and December 1997, there were 30 patients with Stage II (occult) endometrial carcinoma who received postoperative vaginal vault brachytherapy as the only adjuvant treatment. The study group consisted of 15 of these patients who had extended surgical staging (including lymphadenectomy). RESULTS: At a median follow-up of 36 months (range 17 to 113 months), there has been no recurrence. There were no major complications from surgery. Only 1 patient had mild rectal bleeding following vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities. CONCLUSIONS: Extended surgical staging and postoperative vaginal vault brachytherapy for Stage II (occult) endometrial carcinoma is associated with minimal morbidity and excellent survival.
Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias Endometriales/radioterapia , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , VaginaRESUMEN
This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously published data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2000 was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively. All patients presented with a local swelling or a lump. Two had associated discharge and 2 had associated pain. Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the Bartholin gland. None of the patients with SCC developed recurrent disease. The patient with adenoid-cystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine cancer of the Bartholin gland was considered tumour-free after operation. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC.
Asunto(s)
Glándulas Vestibulares Mayores , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/cirugía , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/cirugía , Adulto , Anciano , Biopsia , Terapia Combinada , Femenino , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study. All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived. The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.
Asunto(s)
Carcinoma/cirugía , Neoplasias de las Trompas Uterinas/cirugía , Dolor Abdominal/etiología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/diagnóstico , Carcinoma/patología , Quimioterapia Adyuvante , Diagnóstico Diferencial , Neoplasias de las Trompas Uterinas/diagnóstico , Neoplasias de las Trompas Uterinas/patología , Femenino , Hemorragia/etiología , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system. While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation. Patients with negative washings had a DFS of 96% at 36 months compared with 67% for patients with positive washings (log-rank P<0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor.
Asunto(s)
Adenocarcinoma/patología , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Neoplasias Uterinas/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Adulto , Diferenciación Celular , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Estudios Multicéntricos como Asunto , Pronóstico , Factores de Tiempo , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirugíaRESUMEN
OBJECTIVES: The aim of this study is to examine the patterns of failure after extended surgical staging and postoperative vaginal vault brachytherapy as the only adjuvant treatment in high-risk surgical Stage I patients with endometrial carcinoma. METHODS: The records of all patients with endometrial carcinoma (adenocarcinoma or adenosquamous) receiving vaginal vault brachytherapy as the only adjuvant treatment from January 1989 to December 1997 were examined. A total of 489 patients were found. Of these, 133 had extended surgical staging. The study group consists of 77 surgical Stage I patients with Substages IBG3 and any grade IC. Recurrences were recorded as in the vagina, pelvis, or distant. RESULTS: The mean follow-up interval was 45 months (range 14 to 96 months). Eleven patients had recurrence (14%). Median time to recurrence was 15 months (range 6 to 56 months). Recurrences occurred in the vagina in 7, pelvis in 1, and distantly in 3 patients. Five of 7 vaginal recurrences occurred within 2 years. All patients with distant recurrence died from disease. One patient with pelvic recurrence is alive with disease. Only 1 patient with vaginal recurrence died from disease. Six patients with isolated recurrences in the vagina were successfully treated with radiotherapy with or without local excision. All 6 have no evidence of disease at follow-up (median survival 29 months, range 20 to 71 months). CONCLUSIONS: The vagina remains the most common site of recurrence for high-risk surgical Stage I patients treated with postoperative vaginal vault brachytherapy. Close follow-up in the first 2 years is essential to detect isolated vaginal recurrences. These are amenable to salvage treatment with good disease-free survival.
Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Carcinoma Adenoescamoso/radioterapia , Neoplasias Endometriales/radioterapia , Recurrencia Local de Neoplasia , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/cirugía , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Estadificación de Neoplasias , Radioterapia Adyuvante , Factores de Riesgo , Vagina , Neoplasias Vaginales/radioterapia , Neoplasias Vaginales/secundarioRESUMEN
BACKGROUND: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy. RESULTS: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring.
Asunto(s)
Germinoma/cirugía , Neoplasias Ováricas/cirugía , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Niño , Estudios de Cohortes , Cistectomía/métodos , Femenino , Estudios de Seguimiento , Germinoma/patología , Humanos , Menstruación , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Epiplón/cirugía , Neoplasias Ováricas/patología , Ovariectomía/métodos , Reproducción , Estudios RetrospectivosRESUMEN
Malignant ovarian germ cell tumours (MOGCT) principally occur in girls and young women and are generally unilateral. Effective combination chemotherapy with conservative surgery has seen a dramatic improvement in survival rates. This increase has shifted the focus to long-term fertility and reproductive outcome. The present study describes 45 patients with MOGCT treated with conservative surgery to preserve fertility, with or without the addition of chemotherapy. The age range was 10 to 32 years with a mean of 20 years. The majority of the subjects had Stage 1 tumours; 44 underwent unilateral salpingo-oophorectomy and 1 patient ovarian cystectomy. Adjuvant chemotherapy was administered in 29 patients. Overall mean follow-up was 58.7 months. There were 4 recurrences and 2 deaths. Survival of those with Stage 1 disease was 97% and for advanced stages 87%. During chemotherapy 50% became amenorrhoeic but 96% resumed normal menstrual function on completion. Seven healthy babies were recorded in the chemotherapy group and no documented birth defects occurred in any of these. There was no case of persistent infertility; 3 patients experienced temporary problems. It is concluded that conservative fertility-sparing surgery is the treatment of choice in these young women and advanced disease is not necessarily a contraindication. The majority can anticipate normal menstrual function and fertility.
Asunto(s)
Germinoma/cirugía , Neoplasias Ováricas/cirugía , Adolescente , Adulto , Quimioterapia Adyuvante , Niño , Disgerminoma/cirugía , Trompas Uterinas/cirugía , Femenino , Germinoma/tratamiento farmacológico , Humanos , Menstruación , Recurrencia Local de Neoplasia , Neoplasias Ováricas/tratamiento farmacológico , Ovariectomía , Periodo PosoperatorioRESUMEN
We evaluated the management of patients with microinvasive adenocarcinoma of the cervix (MIAC), in particular, to determine the place of conservative surgery, and determine if the FIGO classification for MIAC is valid and equivalent to the classification as it applies to microinvasive squamous cancer. A review was undertaken of the database of the Queensland Centre for Gynaecological Cancer (QCGC) from January, 1986 to October, 1998. The records of all patients recorded as having MIAC were retrieved. Microinvasion was defined according to the 1995 FIGO classification as a depth of invasion of no greater than 5 mm and a horizontal dimension of no greater than 7 mm 30 patients were found to have been treated for MIAC. The vast majority (29) were asymptomatic, disease being discovered at the time of routine Papanicolaou smear. There was a 43% incidence of coexisting squamous intraepithelial neoplasia. Multifocal disease was found in 17% of patients and lymph-vascular positivity in 7%. Eighteen patients were treated with radical surgery and 13 with conservative surgery. There were no recurrences over a follow-up interval of 3-116 months. Of the 18 patients treated with radical surgery, none was found to have occult microscopic disease in the parametria or nodal metastases. A total of 27 ovaries were removed, all of which were free of disease. In this small study, MIAC appears to behave in a manner similar to the squamous equivalent. The results provide some justification for the FIGO classification of a microinvasive glandular neoplasm of the cervix. There is some support for a role for conservative surgery in managing this condition, but there is insufficient worldwide experience to make definitive recommendations.
Asunto(s)
Adenocarcinoma/terapia , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/terapiaRESUMEN
The syndrome of adenocarcinoma of unknown primary (ACUP) is a frequent problem in both medical and surgical practice. The prognosis is poor, the median lifespan being 4 months. In general, multiple invasive procedures aimed at determining the primary tumour are not warranted due to the low frequency of detecting a tumour for which adequate treatment exists. In this paper we wish to highlight a subset of female patients presenting with malignant ascites and no evidence of a pelvic mass, who on laparotomy were found to have primary peritoneal papillary serous adenocarcinoma. These tumours must be regarded as a potentially treatable subset of patients with ACUP in view of their frequent response to chemotherapy and relatively good prognosis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cistadenocarcinoma Papilar/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Carboplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Papilar/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/mortalidad , Pronóstico , Factores de TiempoRESUMEN
A new treatment for recurrent pelvic lymphocysts is reviewed. Nine women with recurrent symptomatic lymphocyst were treated by marsupialization of the lymphocyst to the peritoneal cavity and functioning omental flap. The omental flap was dissected off the greater curve of the stomach maintaining its blood supply from the appropriate gastroepiploic vessels. The flap functioned by absorbing the lymph that previously accumulated in the lymphocyst. The efficacy of treatment was accessed both clinically and with diagnostic imaging. The pelvic lymphocysts were successfully treated in all 9 cases. There was no significant morbidity and the average hospital stay was 7 days. Marsupialization of pelvic lymphocysts combined with an omental flap is effective, not associated with increased morbidity and has a very low recurrence rate.