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1.
Med Oncol ; 34(8): 134, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28681218

RESUMEN

The aim of this study is to evaluate the outcome and safety of the multidisciplinary strategy using cisplatin plus dose-dense paclitaxel (dose-dense TP) before and after radical hysterectomy (RH) for stage IB2, IIA2, or IIB patients with cervical cancer. In the dose-finding phase, 12 patients received 3 cycles of cisplatin (75 mg/m2, day 1) with paclitaxel (70 or 80 mg/m2, days 1, 8, and 15) every 21 days as neoadjuvant chemotherapy (NAC). In the phase II study, 51 patients received 3 cycles of dose-dense TP at the recommended dose as NAC, and another 2 cycles of the same regimen after RH. The primary endpoint was 2-year progression-free survival (PFS). The secondary endpoints were 2-year overall survival (OS), adverse events (AEs), response rate (RR), and pathological complete response (pCR) rates. The recommended dose of paclitaxel at dose-finding phase was 80 mg/m2. In the phase II study, 34 patients (66.7%) had FIGO stage IIB disease. The RR and pCR rates were 94 and 28%. With a median follow-up duration of 58 months, each of the 2- and 5-year PFS rates was 88.2%, the 2- and 5-year OS rates were 94.1 and 88.2%, respectively. The incidence of grade 3/4 AEs was neutropenia (34%), nausea (12%), appetite loss (10%), fatigue (6%), and anemia (6%). Febrile neutropenia was uncommon (2%). Dose-dense TP before and after RH achieved a good long-term survival and was feasible for patients with locally advanced cervical cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología
2.
Jpn J Clin Oncol ; 46(6): 517-21, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26977055

RESUMEN

OBJECTIVE: The purpose of this study is to investigate the clinical characteristics to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. METHODS: We reviewed the charts of women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who underwent interval debulking surgery following neoadjuvant chemotherapy at our cancer center from April 2006 to April 2014. RESULTS: There were 139 patients, including 91 with ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) Stage IIIc in 56 and IV in 35], two with fallopian tube cancers (FIGO Stage IV, both) and 46 with primary peritoneal cancer (FIGO Stage IIIc in 27 and IV in 19). After 3-6 cycles (median, 4 cycles) of platinum-based chemotherapy, interval debulking surgery was performed. Sixty-seven patients (48.2%) achieved complete resection of all macroscopic disease, while 72 did not. More patients with cancer antigen 125 levels ≤25.8 mg/dl at pre-interval debulking surgery achieved complete resection than those with higher cancer antigen 125 levels (84.7 vs. 21.3%; P< 0.0001). Patients with no ascites at pre-interval debulking surgery also achieved a higher complete resection rate (63.5 vs. 34.1%; P< 0.0001). Moreover, most patients (86.7%) with cancer antigen 125 levels ≤25.8 mg/dl and no ascites at pre-interval debulking surgery achieved complete resection. CONCLUSIONS: A low cancer antigen 125 level of ≤25.8 mg/dl and the absence of ascites at pre-interval debulking surgery are major predictive factors for complete resection during interval debulking surgery and present useful criteria to determine the optimal timing of interval debulking surgery.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Área Bajo la Curva , Ascitis , Antígeno Ca-125/análisis , Carcinoma Epitelial de Ovario , Procedimientos Quirúrgicos de Citorreducción , Neoplasias de las Trompas Uterinas/complicaciones , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/complicaciones , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/cirugía , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Curva ROC , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo
3.
Diagn Cytopathol ; 43(10): 791-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26173165

RESUMEN

BACKGROUND: Gastric-type mucinous carcinoma (GAS) is a clinically aggressive variant of cervical adenocarcinoma. This study sought to describe the cytologic features of GAS. METHODS: We reviewed the cervical and endometrial smears of 14 patients with a histopathologic diagnosis of GAS. All slides were conventionally smeared. We included 20 controls with usual-type endocervical adenocarcinoma (UEA). RESULTS: Monolayered and honeycomb sheets were observed in 78.6% (11/14) of patients with GAS, and were prominent in seven patients. Three-dimensional clusters were more prominent in the UEA group. Vacuolar and/or foamy cytoplasm was observed in 71.4% (10/14) of patients with GAS, whereas this finding was rare among those with UEA (2/18). Marked intracytoplasmic neutrophil entrapment was more common in the GAS group (7/14) than in the UEA group (2/18). Intracytoplasmic mucin was present in eight patients with GAS. Nuclei were vesicular in eight patients with GAS, but were homogenous and hyperchromatic in UEA patients. Conspicuous nucleoli were present in nine patients with GAS. Conversely, this finding was rarely observed in UEA patients. CONCLUSIONS: The characteristic cytologic findings of GAS include (1) monolayered and honeycomb sheets, (2) vacuolar and/or foamy cytoplasm, (3) intracytoplasmic neutrophil entrapment, and (4) vesicular nuclei with prominent nucleoli.


Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Cuello del Útero/citología , Cuello del Útero/patología , Neoplasias del Cuello Uterino/diagnóstico , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou , Neoplasias del Cuello Uterino/patología , Frotis Vaginal
4.
Int J Gynecol Cancer ; 25(7): 1300-5, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26166556

RESUMEN

OBJECTIVE: Neuroendocrine carcinoma of the cervix is a rare and aggressive subtype of cervical cancer and includes small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). We conducted a single-institution retrospective review to explore the pattern of treatments and outcomes with the aim of defining an optimum treatment strategy for these carcinomas. METHODS: Twenty-three consecutive patients with SCNEC or LCNEC of the cervix diagnosed at the Hyogo Cancer Center between 1996 and 2013 were included in this study. Pertinent information, including clinical and pathological characteristics, and survival data were collected from clinical records and/or telephone surveys. The pathological review was conducted by a pathologist specializing in gynecologic cancer. RESULTS: Eleven patients had SCNEC and 12 had LCNEC. Eighteen patients with International Federation of Gynecology and Obstetrics (FIGO) stage I/II underwent type III radical hysterectomy with pelvic lymphadenectomy. After surgery, 9 received adjuvant chemotherapy (8, irinotecan plus cisplatin; 1, paclitaxel plus carboplatin), 7 received concurrent chemoradiation therapy (CCRT; 6, nedaplatin; 1, cisplatin), and 2 received radiation therapy (RT). Patients who received adjuvant chemotherapy had a better overall survival than did patients who received CCRT or RT (hazard ratio, 0.21; 95% confidence interval, 0.030-1.51; P = 0.12). Although the overall survival rates are not statistically significant, the 9 patients who underwent radical hysterectomy followed by adjuvant chemotherapy are all alive. Among the remaining 5 patients who did not undergo radical hysterectomy, 2 with FIGO stage III and 1 with stage IVa received CCRT, and 2 with stage IVb received palliative RT or chemotherapy. These 5 patients with FIGO stage III/IV died of disease within 36 months. CONCLUSIONS: Radical hysterectomy followed by platinum-based chemotherapy, especially the irinotecan plus cisplatin combination, is beneficial for long-term survival in patients with early-stage neuroendocrine carcinoma of the cervix.


Asunto(s)
Carcinoma de Células Grandes/patología , Carcinoma Neuroendocrino/patología , Carcinoma de Células Pequeñas/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Carcinoma de Células Grandes/mortalidad , Carcinoma de Células Grandes/terapia , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/terapia , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/terapia , Terapia Combinada , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapia
5.
Cancer Chemother Pharmacol ; 76(2): 335-42, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26092322

RESUMEN

PURPOSE: We previously reported that the concept of "platinum sensitivity" could be applied to recurrent endometrial cancer. We conducted an ancillary analysis to determine an appropriate second-line regimen for patients who received a platinum agent as first-line chemotherapy. METHODS: We extracted and reanalyzed data of patients treated with doxorubicin and cisplatin (AP), paclitaxel and carboplatin (TC), or docetaxel and carboplatin (DC) as first- and second-line chemotherapies from the SGSG012/GOTIC004/Intergroup study. RESULTS: We identified 216 patients: 38 received AP as first-line chemotherapy, of which 36 received TC or DC (Tax-C) as second-line chemotherapy; and 178 received Tax-C as first-line chemotherapy, of which 51 received AP and 127 received Tax-C as second-line chemotherapy. Median progression-free survival (PFS) and overall survival (OS) after second-line chemotherapy decreased in the order of Tax-C followed by Tax-C (10 and 48 months, respectively), AP followed by Tax-C (9 and 23 months, respectively), and Tax-C followed by AP (3 and 12 months, respectively). Median PFS and OS after second-line chemotherapy for platinum-resistant patients receiving Tax-C as first-line chemotherapy were longer in Tax-C than in AP (7 and 23 vs. 3 and 10 months, respectively) as second-line chemotherapy [hazard ratio (HR) 3.255, 95 % confidence interval (CI) 1.908-5.555, p < 0.0001; HR 3.179, 95 % CI 1.835-5.507, p < 0.0001, respectively]. Median PFS and OS after second-line chemotherapy for platinum-sensitive patients receiving Tax-C as first-line chemotherapy were almost equivalent to those receiving Tax-C or AP as second-line chemotherapy. CONCLUSIONS: For platinum-resistant recurrent endometrial cancer patients, Tax-C may be preferred over AP as second-line chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Resistencia a Antineoplásicos , Neoplasias Endometriales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Recurrencia Local de Neoplasia/patología , Paclitaxel/administración & dosificación , Estudios Retrospectivos , Taxoides/administración & dosificación
6.
Gynecol Oncol ; 137(1): 34-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25662625

RESUMEN

OBJECTIVE: In order to determine indications for less radical surgery such as modified radical hysterectomy, the risk of pathological parametrial involvement and prognosis of FIGO stage IB1 cervical cancer patients undergoing standard radical hysterectomy with pre-operatively assessed tumor diameter≤2 cm were investigated. METHODS: We conducted a retrospective multi-institutional chart review of patients with FIGO stage IB1 cervical cancer who underwent primary surgical treatment between 1998 and 2002. The eligibility criteria for the analyses were (i) histologically-proven squamous cell carcinoma, adenocarcinoma or, adenosquamous cell carcinoma, (ii) radical hysterectomy performed, (iii) clinical tumor diameter data available by MR imaging or specimens by cone biopsy, and (iv) age between 20 and 70. Based on the clinical tumor diameter, patients were stratified into those with the following tumors: i) 2 cm or less (cT≤2 cm) and ii) greater than 2 cm (cT>2 cm). We expected 5-year OS of ≥95% and parametrial involvement<2-3% for patients with cT≤2 cm who underwent radical hysterectomy. RESULTS: Of the 1269 patients enrolled, 604 were eligible for the planned analyses. Among these, 571 underwent radical hysterectomy (323 with cT≤2 cm and 248 with cT>2 cm). Parametrial involvement was present in 1.9% (6/323) with cT≤2 cm and 12.9% (32/248) with cT>2 cm. Five-year overall survivals were 95.8% (95% CI 92.9-97.6%) in cT≤2 cm and 91.9% (95% CI 87.6-94.8%) in cT>2 cm patients. CONCLUSION: Patients with cT≤2 cm had lower risk of parametrial involvement and more favorable 5-year overall survival. They could therefore be good candidates for receiving less radical surgery.


Asunto(s)
Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Conización , Femenino , Humanos , Histerectomía/métodos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía , Adulto Joven
7.
Int J Clin Oncol ; 20(3): 566-73, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25030546

RESUMEN

BACKGROUND: Platinum agents are essential for treating gynecological malignancies, particularly ovarian cancer. However, multiple carboplatin doses may cause hypersensitivity reactions (HSRs). Carboplatin desensitization prevents life-threatening HSRs and promotes the successful completion of planned chemotherapy. METHODS: Since January 2010, carboplatin desensitization was performed at our institution. Solutions with 1/1000, 1/100, and 1/10 dilutions of carboplatin and an undiluted solution were prepared in 250 mL of 5% glucose. Each solution was administered as a 1-h intravenous infusion (4-step 4-h protocol). This retrospective analysis was approved by the institutional review board. RESULTS: From January 2010 to December 2013, 20 patients with gynecological malignancies (median age 62 years, range 43-74 years) received desensitization treatment. The International Federation of Gynecology and Obstetrics stages at presentation were I, II, III, and IV in 1, 1, 15, 13 patients, respectively. During first-line and second-line treatments, 3 and 17 patients, respectively, experienced carboplatin-induced HSRs. The median carboplatin cycle number was 11 (range 2-16). In the first desensitization cycle, 17 (85%) patients completed treatment without adverse events, 2 experienced Grade 1 HSRs but completed treatment, and 1 experienced Grade 3 HSR and discontinued treatment. The first desensitization cycle completion rate was 95%. Of 83 desensitization cycles administered, 79 (95.2%) were completed. No treatment-related deaths occurred. CONCLUSIONS: Most patients completed the planned chemotherapy. Our protocol could be conducted safely with shorter duration and simpler procedures than previous protocols. Carboplatin desensitization seems beneficial for patients with a history of carboplatin-induced HSRs; however, the risk of HSR recurrence still remains. Desensitization should therefore be performed only by well-trained staff.


Asunto(s)
Carboplatino/efectos adversos , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/terapia , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Adulto , Anciano , Carboplatino/uso terapéutico , Hipersensibilidad a las Drogas/etiología , Femenino , Humanos , Persona de Mediana Edad , Compuestos de Platino/efectos adversos , Estudios Retrospectivos
8.
Jpn J Clin Oncol ; 44(10): 1000-3, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25098705

RESUMEN

We have developed a collaborative hospital-based approach to monitoring the impact of a human papillomavirus vaccine on cervical cancer, its precursor lesions and human papillomavirus type-specific prevalence in Japan. The monitoring will be conducted for a total period of 21 years on women aged <40 who are newly diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia or adenocarcinoma in situ at 21 participating institutes. Women are monitored to determine their vaccine history and will be human papillomavirus-genotyped each year. The primary endpoint is the human papillomavirus16/human papillomavirus18-positive rate in women aged 16-25 who are diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia grade 2/3 and adenocarcinoma in situ. The major secondary endpoints are the number of women aged <40 who are diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia grade 2/3 and adenocarcinoma in situ, the human papillomavirus type-specific prevalence, and the number of deaths from invasive cervical cancer in women aged <40. Long-term surveillance for human papillomavirus-associated cervical diseases in young females is important for the development of future strategies for cervical cancer prevention in Japan.


Asunto(s)
Vacunación Masiva , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adenocarcinoma in Situ/prevención & control , Adenocarcinoma in Situ/virología , Adolescente , Adulto , Femenino , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Japón , Evaluación de Programas y Proyectos de Salud , Proyectos de Investigación , Adulto Joven , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virología
9.
Gynecol Oncol Case Rep ; 8: 24-6, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24707459

RESUMEN

•A 59-year-old postmenopausal woman had ovarian clear cell adenocarcinoma producing AFP.•The tumor lacked a yolk sac component and formed ducts similar to the fetal gut.

10.
World J Oncol ; 5(2): 62-67, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29147379

RESUMEN

BACKGROUND: Currently, there is no standardized follow-up protocol for patients who undergo laser conization. Therefore, we retrospectively investigated the clinical outcomes of laser conization in patients with high-grade cervical intraepithelial neoplasia 2-3 (CIN 2-3) and microinvasive squamous cell carcinoma and assessed the risks of residual and recurrent lesions of the cervix uteri. METHODS: The medical and pathological records of 91 patients with CIN 2, 580 with CIN 3 and 73 with microinvasive cervical cancer (MIC) who underwent laser conization between January 2000 and December 2011 were retrospectively reviewed. RESULTS: Positive margins increased with the extent of disease and were observed in 5.5%, 8.9% and 16.4% patients with CIN 2, CIN 3 and MIC, respectively, while residual or recurrent disease was observed in 0%, 3.2% and 13.6% patients, respectively. Examination of specimens obtained through postconization biopsy or hysterectomy revealed that 1.5% and 20% patients with negative and positive margins, respectively, were diagnosed with residual or recurrent lesions. Among patients who were conservatively managed after conization, seven with CIN 3 exhibited residual or recurrent disease, as evidenced by abnormal cytological findings, within 2 years after conization. CONCLUSIONS: Continuous follow-up by cytology and colposcopy, particularly during the first 2 years after conization, can effectively detect early residual or recurrent disease in CIN 3 and MIC patients, regardless of their margin status.

11.
Gynecol Oncol ; 131(3): 531-4, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24096109

RESUMEN

OBJECTIVE: To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery. METHODS: Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: The 124 enrolled patients had a median age of 62 years (range, 35-79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR]=1.94, p=0.003), residual cancer at the end of surgery ≥1cm (HR=3.78, p<0.001), and histological grade 0-1 (HR=1.65, p=0.03) were independent predictors of decreased OS. Grade 0-1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio=8.42, p=0.003). CONCLUSIONS: Residual disease of ≥1cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Adulto , Anciano , Carboplatino/administración & dosificación , Carcinoma Epitelial de Ovario , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento
12.
Transl Res ; 162(3): 181-90, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23856093

RESUMEN

Ovarian cancer is the most lethal gynecological malignancy in the western world. Although patients with early-stage ovarian cancer generally have a good prognosis, approximately 20%-30% of patients will die of the disease, and 5-year recurrence rates are 25%-45%, highlighting the need for improved detection and treatment. We investigated the role of VAV1, a protein with guanine nucleotide exchange factor activity, which is associated with survival in patients with early-stage ovarian cancer (International of Obstetrics and Gynecology [FIGO] stages I and II). We analyzed 88 samples from patients with primary epithelial ovarian cancer, which were divided into FIGO stages I and II (n = 46), and III and IV (n = 42). Prognostic analysis revealed that upregulated VAV1 expression correlated significantly with poor prognosis in patients with early-stage epithelial ovarian cancer (P ≤ 0.05), but not with other clinicopathologic features. Stable overexpression of VAV1 in human high-grade serous ovarian cancer SKOV3 cells induced morphologic changes indicative of loss of intercellular adhesions and organized actin stress fibers. Western blotting and real-time reverse transcriptase-polymerase chain reaction demonstrated that these cells had downregulated E-cadherin protein and messenger RNA levels, respectively. This downregulation is associated with epithelial-mesenchymal transition (EMT) and invasive cancer. Furthermore, VAV1 overexpression in both SKOV3 and human ovarian surface epithelial cells demonstrated that its upregulation of an E-cadherin transcriptional repressor, Snail and Slug, was not confined to ovarian cancer cells. Conversely, knockdown of VAV1 by RNA interference reduced Snail and Slug. Our findings suggest that VAV1 may play a role in the EMT of ovarian cancer, and may serve as a potential therapeutic target.


Asunto(s)
Cadherinas/metabolismo , Transición Epitelial-Mesenquimal , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-vav/fisiología , Factores de Transcripción/metabolismo , Carcinoma Epitelial de Ovario , Regulación hacia Abajo , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Factores de Transcripción de la Familia Snail
13.
Int J Gynecol Cancer ; 23(6): 1084-91, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23792604

RESUMEN

OBJECTIVE: Cervical cancer is the second most common cancer in females worldwide, and the majority of squamous cell carcinomas and adenocarcinomas are associated with high-risk human papillomavirus (HPV) infection. However, the relationship between clear cell carcinoma of the cervix (CCCC) and HPV is unclear. In this study, we sought to determine if HPV infection is associated with CCCC and to elucidate the signaling pathways involved. METHODS: We collected samples from 13 CCCC patients and collated the relevant clinicopathologic data. We then evaluated the presence of HPV types 16, 18, 31, 33, 35, 52, and 58 by broad-spectrum amplification by polymerase chain reaction and HPV types 39, 45, 51, 56, 59, and 68 by nested polymerase chain reaction assay that combines degenerate E6/E7 consensus primers and type-specific primers from extracted genomic DNA. Immunohistochemistry was used to analyze the expression of EGFR (epidermal growth factor receptor), HER2, PTEN (phosphatase and tensin homolog), phospho-AKT, phospho-mTOR (mammalian target of rapamycin), p16, and p53. EGFR and HER2 gene amplification was determined by fluorescence in situ hybridization. RESULTS: Patients with stage IB CCCC had a better 3-year overall survival rate compared with those with advanced-stage cancer (100% vs 44%; P = 0.014). High-risk HPVs were not detected in any of the cases examined. EGFR immunostaining was observed in 9 (75%) of 12 patients, HER2 in 3 (25%) of 12, PTEN in 6 (50%) of 12, and phospho-AKT in 7 (58%) of 12, and phospho-mTOR in 6 (50%) of 12. EGFR amplification could not be detected, but HER2 amplification was identified in 1 of (12.5%) 8 cases. CONCLUSIONS: Patients with stage I CCCC demonstrated good overall survival and rare recurrence. Clear cell carcinoma of the cervix is unrelated to high-risk HPV infection; hence, current vaccines will not prevent the incidence of CCCC. However, increased EGFR or HER2 expression or activation of AKT or mTOR was observed in all cases, indicating that inhibitors of tyrosine kinases or the AKT-mTOR pathway may be suitable treatment regimens for CCCC.


Asunto(s)
Adenocarcinoma de Células Claras/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Papillomaviridae/genética , Infecciones por Papillomavirus/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/virología , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Estudios de Seguimiento , Amplificación de Genes , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología , Estadificación de Neoplasias , Fosfohidrolasa PTEN/metabolismo , Infecciones por Papillomavirus/mortalidad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Fosforilación , Reacción en Cadena de la Polimerasa , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Transducción de Señal , Tasa de Supervivencia , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología
14.
Arch Gynecol Obstet ; 288(2): 385-91, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23435725

RESUMEN

PURPOSE: Endometrial stromal sarcomas (ESSs) are rare tumors and are divided into two groups: low-grade endometrial stromal sarcoma (ESS-LG) and undifferentiated endometrial sarcoma (UES). The purpose of this study was to compare the clinicopathological features and immunophenotypes of ESS-LG and UES. METHODS: The authors evaluated 16 patients diagnosed with ESS at the Hyogo Cancer Center, reviewed their files and data, and performed an immunohistochemical study for oncogenic proteins (EGFR, PDGFR-α, and PDGFR-ß) and cell cycle regulators (cyclin D1, cyclin E, p16(INK4a), p21(cip1), p27(kip1), and p53) to compare ESS-LG and UES using the World Health Organization (WHO) classification. RESULTS: Four cases (25 %) were classified as ESS-LGs and 12 (75 %) as UES. Patients with UES had a significantly worse overall survival than did those with ESS-LG (p = 0.0445). Although no ESS-LGs showed expression of p16(INK4a), 10 of 12 (83 %) UESs showed expression of p16(INK4a). UESs showed a trend toward higher expression of cyclin D1, p21(cip1), and p53 compared with ESS-LGs. CONCLUSIONS: Our data emphasize the clinical importance of the WHO classification of ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.


Asunto(s)
Tumores Estromáticos Endometriales/metabolismo , Tumores Estromáticos Endometriales/patología , Sarcoma/metabolismo , Sarcoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Ciclina D1/metabolismo , Ciclina E/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Tumores Estromáticos Endometriales/terapia , Receptores ErbB/metabolismo , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Persona de Mediana Edad , Clasificación del Tumor , Ovariectomía , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Salpingectomía , Sarcoma/terapia , Estadísticas no Paramétricas , Proteína p53 Supresora de Tumor/metabolismo
15.
J Cancer ; 3: 191-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22606208

RESUMEN

AIM: To evaluate the effect of abdominal radical trachelectomy on ovarian reserve and compare it with abdominal radical hysterectomy and a control group that did not have surgery. METHOD: We enrolled eighteen women who had abdominal radical trachelectomy with pelvic lymphadenectomy and sixteen patients who had abdominal radical hysterectomy for this study. Ten thousand one hundred eighty-six women were also included as a control group for comparison. The Mann-Whitney U test was used for comparison of patient characteristics and comparison of serum anti-Müllerian hormone levels between the three groups. RESULTS: Serum anti-Müllerian hormone levels in patients with abdominal radical trachelectomy were significantly higher than those of patients with abdominal radical hysterectomy (P<0.05). Serum anti-Müllerian hormone levels in the abdominal radical hysterectomy group were significantly lower than those in the control group (P=0.02), with no significant difference between the abdominal radical trachelectomy and control groups. These data indicated that abdominal radical trachelectomy did not affect ovarian function with respect to ovarian reserve and the response to ovarian stimulation. CONCLUSIONS: Serum anti-Müllerian hormone levels could be useful as a marker of ovarian reserve after abdominal radical trachelectomy. It is important to avoid postoperative complications causing a reduction in ovarian function to accomplish fertility-sparing surgery.

16.
Int J Gynecol Cancer ; 22(3): 479-83, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22214963

RESUMEN

OBJECTIVE: The purpose of this study was to compare surgical outcomes using modified (type II) and traditional (type III) abdominal radical trachelectomy (ART) for fertility-sparing surgery in early cervical cancer. METHODS: A prospectively maintained database of ART procedures was analyzed. Data were collected regarding age, stage, histology, operative outcome, surgical complication, and fertility outcome. RESULTS: We performed 23 fertility-sparing ARTs for patients with International Federation of Gynecology and Obstetrics stages IA to IB1 tumors of less than 2 cm between 2006 and 2010. Type III ART was attempted in 8 patients and modified ART in 15 patients. The median operating time was greater in the type III group compared with that in the type II group (305 vs 247 minutes; P < 0.02). The median surgical blood loss was greater in the type III ART group (580 mL; range, 250-988 mL) compared with that in the modified type II group (366 mL; range, 200-850 mL; P < 0.05). The median time to recovery of bladder dysfunction was less in the type II group (9 days; range, 3-10 days) than that in the type III group (13 days; range, 10-23 days; P < 0.01). There were no recurrences at the time of this report. CONCLUSIONS: Type II ART provides surgical and pathological outcomes with better recovery of bladder function similar to those in type III ART. For patients with early cervical cancer who wish to preserve reproductive function, type II ART is a feasible and safe operation.


Asunto(s)
Cavidad Abdominal/cirugía , Adenocarcinoma/cirugía , Preservación de la Fertilidad/métodos , Procedimientos Quirúrgicos Ginecológicos/métodos , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adulto , Detección Precoz del Cáncer , Estudios de Factibilidad , Femenino , Humanos , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología
17.
J Cancer ; 3: 14-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22211141

RESUMEN

A choriocarcinoma component with a malignant tumor is relatively rare. We present a case of an 85-year-old woman with mixed carcinoma, which was endometrioid adenocarcinoma with squamous differentiation, choriocarcinoma and a disseminated peritoneal nodule, which was papillary serous adenocarcinoma. The patient received surgery and conservative treatment. Twenty weeks after surgery, a recurring tumor appeared at the Douglas pouch. Histology showed that the recurring tumor was poorly differentiated carcinoma that was very different from the primary tumor. This case represents an unusual uterine corpus cancer with high-grade transformation with serous and choriocarcinomatous differentiation. This case also demonstrates the capacity of tumor cells to differentiate into divergent elements.

18.
Gan To Kagaku Ryoho ; 38(8): 1337-40, 2011 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-21829076

RESUMEN

A 65-year-old female was admitted to our hospital with abdominal distension. Abdominal CT and MRI revealed massive ascites and an omental cake, but the ovaries were of normal size. After an omentum biopsy was performed during open abdominal surgery, she was diagnosed as peritoneal serous papillary adenocarcinoma. After 6 courses of chemotherapy with paclitaxel and carboplatin, the massive ascites totally disappeared, and a second look operation could be performed. She is still alive with no sign of recurrence.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma Papilar/tratamiento farmacológico , Paclitaxel/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Membrana Serosa/patología , Anciano , Biopsia , Carboplatino/administración & dosificación , Carcinoma Papilar/cirugía , Terapia Combinada , Femenino , Humanos , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , Tomógrafos Computarizados por Rayos X
19.
Int J Gynecol Cancer ; 21(2): 349-54, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21721193

RESUMEN

BACKGROUND: In the surgical treatment for early-stage cervical carcinoma, it is important to identify preoperatively a low-risk group of patients as candidates for less radical surgery to avoid the morbidity associated with radical hysterectomy. The aim of this study was to evaluate the correlation between tumor diameter measured preoperatively using magnetic resonance imaging (MRI) and pathological prognostic factors in International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical carcinoma. METHODS: A total of 125 patients with FIGO stage IB1 cervical cancer were included in this study. Clinical records, pathology reports, and MRI findings were retrospectively reviewed. RESULTS: Histological diagnosis was squamous cell carcinoma in 57 patients and non squamous cell carcinoma in 68 patients. All patients underwent preoperative evaluation by MRI within a median period of 13.5 days before surgery. The tumor diameter measured by MRI ranged from zero (no tumor detected) to 42 mm, with a median of 23 mm.Pathological prognostic factors included parametrial involvement, lymph node metastasis,deep stromal invasion, and lymphovascular space invasion. All these factors were found less frequently in patients with a smaller tumor diameter. Most notably, parametrial involvement was seen in none of the patients with tumors 20 mm or less and was detected only in patients with tumors greater than 20 mm (P = 0.01). CONCLUSIONS: In the FIGO stage IB1 cervical carcinoma, the tumor diameter measured preoperatively by MRI correlates well with other pathological prognostic factors, especially with parametrial involvement. This finding suggests that the tumor diameter measured in preoperative MRI may serve as a strong predictor of parametrial involvement in FIGO stage IB1 cervical carcinoma, which can be used to select a candidate population for less radical surgery without the need for a cone biopsy before hysterectomy.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Diafragma Pélvico/patología , Carga Tumoral , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto Joven
20.
Int J Gynecol Cancer ; 19(4): 723-7, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19509578

RESUMEN

The purpose of this study was to evaluate the use of concurrent chemoradiotherapy involving weekly administration of cisplatin and paclitaxel for the treatment of locally advanced cervical carcinoma in Japanese women. Twenty Japanese patients were registered for this phase I study. Radiation therapy was performed using external irradiation and high-dose rate intracavitary irradiation of the pelvis. Chemotherapy was performed once a week until termination of the radiation therapy. The dose of cisplatin was decided as 30 mg/m2, and the initial dose of paclitaxel was set as 30 mg/m2, with a planned incremental increase of 10 mg/m2 up to 70 mg/m2. When 3 to 6 patients were registered at each dose level and dose-limiting toxicity (DLT) was noted in more than 3 patients, the dose level was assumed to be the maximum tolerated dose. Among the 20 patients, 1 patient experienced DLT during 2 courses because of dehydration and arrhythmia. In another patient, chemotherapy was discontinued after 4 courses because of a hypersensitivity reaction to paclitaxel at dose level 3. No patient experienced DLT resulting from hematologic toxicities. All patients underwent radiation therapy according to schedule without any discontinuations. A complete response was obtained in 16 patients. Based on the results obtained from this study, weekly administration of 30 mg/m2 cisplatin and 50 mg/m2 paclitaxel with concurrent chemoradiotherapy can be considered a tolerable and safe dose for the treatment of locally advanced cervical carcinoma in Japanese women.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Braquiterapia , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Adulto Joven
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