RESUMO
OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort nâ¯=â¯1196, and Japan cohort nâ¯=â¯495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (Pâ¯=â¯0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, Pâ¯=â¯0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, Pâ¯=â¯0.805), overall survival (HR not estimated, Pâ¯=â¯0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, Pâ¯=â¯0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, Pâ¯=â¯0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, Pâ¯=â¯0.021), but was not associated with overall survival (HR not estimated, Pâ¯=â¯0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9â¯years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.
Assuntos
Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/terapia , Segunda Neoplasia Primária/epidemiologia , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Ovário/fisiologia , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Japão/epidemiologia , Gradação de Tumores , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.
Assuntos
Carcinossarcoma/secundário , Neoplasias Uterinas/patologia , Carcinossarcoma/mortalidade , Carcinossarcoma/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/cirurgiaRESUMO
OBJECTIVE: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.
Assuntos
Vasos Sanguíneos/patologia , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Vasos Linfáticos/patologia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Quimioterapia Adjuvante , Progressão da Doença , Feminino , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Intervalo Livre de Progressão , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) and to examine the association of VTE and survival in women with uterine carcinosarcoma. METHODS: This multicenter retrospective study examined 906 women who underwent primary surgical treatment for stage I-IV uterine carcinosarcoma. Time-dependent analyses were performed for cumulative incidence of VTE after surgery on multivariate models. RESULTS: There were 72 (7.9%) women who developed VTE after surgery with 1-, 2-, and 5-year cumulative incidences being 5.1%, 7.3%, and 10.2%, respectively. On multivariate analysis, older age (hazard ratio [HR] per year 1.03, P=0.012), non-Asian race (HR 6.28, P<0.001), large body habitus (HR per kg/m2 1.04, P=0.014), residual disease at surgery (HR 3.04, P=0.003), tumor size ≥5cm (HR 2.73, P=0.003), and stage IV disease (HR 2.12, P=0.025) were independently associated with increased risk of developing VTE. A risk pattern analysis identified that obese Non-Asian women with large tumors (13.7% of population) had the highest incidence of VTE (2-year cumulative rate, 26.1%) whereas Asian women with no residual disease (47.1% of population) had the lowest (2-year cumulative rate, 1.6%) (P<0.001). Presence of carcinoma/sarcoma in metastatic sites was significantly associated with increased risk of VTE compared to carcinoma alone (2-year rates, 31.2% versus 8.4%, P=0.049). VTE was independently associated with decreased progression-free survival on multivariate models (5-year rates, 24.9% versus 47.2%, HR 1.46, 95%CI 1.05-2.04, P=0.026). CONCLUSION: Our study suggests that VTE represents a surrogate marker of aggressive tumor behavior and diminished patient condition in uterine carcinosarcoma; obese Non-Asian women with large tumors carry a disproportionally high risk of VTE, suggesting that long-term prophylaxis may benefit this population.
Assuntos
Carcinossarcoma/cirurgia , Complicações Pós-Operatórias/etiologia , Neoplasias Uterinas/cirurgia , Tromboembolia Venosa/etiologia , Idoso , Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasia Residual , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Tromboembolia Venosa/mortalidadeRESUMO
BACKGROUND AND OBJECTIVES: To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. METHODS: This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. RESULTS: The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. CONCLUSION: Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/mortalidade , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/mortalidade , Carboplatina/administração & dosagem , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Estudos de Casos e Controles , Quimioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgiaRESUMO
OBJECTIVE: To examine tumor characteristics and survival outcome of women with uterine carcinosarcoma who had a history of tamoxifen use. METHODS: This is a multicenter retrospective study examining stage I-IV uterine carcinosarcoma cases based on history of tamoxifen use. Patient demographics, tumor characteristics, treatment pattern, and survival outcomes were compared between tamoxifen users and non-users. RESULTS: Sixty-six cases of tamoxifen-related uterine carcinosarcoma were compared to 1009 cases with no history of tamoxifen use. Tamoxifen users were more likely to be older (mean age, 69 versus 64, P<0.001) and had a past history of malignancy (100% versus 12.7%, P<0.001). Tamoxifen-related uterine carcinosarcoma was significantly associated with a higher proportion of stage IA disease (48.4% versus 29.9%) and a lower risk of stage IVB disease (7.8% versus 16.0%) compared to tamoxifen-unrelated carcinosarcoma (P=0.034). Deep myometrial tumor invasion was less common in uterine carcinosarcoma related to tamoxifen use (28.3% versus 48.8%, P=0.002). On univariate analysis, tamoxifen use was not associated with progression-free survival (5-year rates 44.5% versus 46.8%, P=0.48) and disease-specific survival (64.0% versus 59.1%, P=0.39). After adjusting for age, past history of malignancy, stage, residual disease status at surgery, and postoperative treatment patterns, tamoxifen use was not associated with progression-free survival (adjusted-hazard ratio 0.86, 95% confidence interval 0.50 to 1.50, P=0.60) and disease-specific survival (adjusted-hazard ratio 0.68, 95% confidence interval 0.36 to 1.29, P=0.24). CONCLUSION: Our study suggests that tamoxifen-related uterine carcinosarcoma may have favorable tumor characteristics but have comparable stage-specific survival outcomes compared to tamoxifen-unrelated uterine carcinosarcoma.
Assuntos
Carcinossarcoma/induzido quimicamente , Antagonistas de Estrogênios/efeitos adversos , Tamoxifeno/efeitos adversos , Neoplasias Uterinas/induzido quimicamente , Idoso , Neoplasias da Mama/tratamento farmacológico , Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
BACKGROUND: To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. METHODS: We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. RESULTS: The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27-0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13-1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02-0.90; P=0.013) but not in none/single factor (P=0.36). CONCLUSION: Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia/métodos , Carcinossarcoma/terapia , Histerectomia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Uterinas/terapia , Carcinossarcoma/patologia , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. METHODS: We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. RESULTS: There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, P<0.001). On multivariate analysis, use of taxane/platinum regimen was independently associated with improved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P=0.02). When stratified by disease-free interval, women with a disease-free interval ≥6months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P=0.002); conversely, in women with a disease-free interval <6months, 2-year SAR rates were similar between the two groups (20.5% versus 18.4%, HR 0.80, 95% CI 0.33 to 1.90, P=0.61). Among women who received a taxane/platinum doublet as adjuvant chemotherapy, re-treatment with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P=0.019). CONCLUSION: Our study suggests that taxane/platinum doublet may be a more effective chemotherapy regimen compared to other regimens among women with recurrent uterine carcinosarcoma, especially for those who had a disease-free interval of ≥6months.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinossarcoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinossarcoma/mortalidade , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Compostos Organoplatínicos/administração & dosagem , Estudos Retrospectivos , Terapia de Salvação , Taxoides/administração & dosagem , Estados Unidos/epidemiologia , Neoplasias Uterinas/mortalidadeRESUMO
OBJECTIVE: Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma. METHODS: Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes. RESULTS: LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r=0.31, p=0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93-20.4, p=0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p=0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54-5.88, p=0.001) and overall survival (HR 2.69, 95%CI 1.18-6.23, p=0.021) while ER-expression did not remain as a significant variable in multivariate analysis. CONCLUSION: Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Vasos Sanguíneos/patologia , Cistadenocarcinoma Seroso/metabolismo , Receptor alfa de Estrogênio/metabolismo , Linfonodos/patologia , Vasos Linfáticos/patologia , Neoplasias Ovarianas/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Idoso , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Receptores ErbB/metabolismo , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Razão de Chances , Neoplasias Ovarianas/patologia , Pelve , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVES: Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer. METHODS: Patients who underwent primary cytoreductive surgery were included in the analysis (n = 276). The enumeration and speciation of pathogens, antimicrobial agents used, and sensitivity assay results were culled from medical records and correlated to clinicopathologic demographics and survival outcomes. Perioperative infection was determined as a positive microbiology result obtained within a 6-week postoperative period. RESULTS: The incidence of perioperative infection was 15.9% (common sites: urinary tract, 57.3%, and surgical wound, 21.4%). Commonly isolated pathogens were Enterococcus species (22.4%) and Escherichia coli (19.4%) in urinary tract infection, and Bacteroides fragilis, E. coli, and Klebsiella pneumoniae (all, 16%) in surgical wound infection. Imipenem represents one of the least resistant antimicrobial agents commonly seen in urinary tract and surgical wound infections in our institution. Perioperative infection was associated with diabetes, serous histology, lymph node metastasis, bowel resection, decreased bicarbonate, and elevated serum urea nitrogen in multivariate analysis. Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival (median time, 8.4 vs 17.6 months; P < 0.001), and decreased overall survival (29.0 vs 51.8 months; P = 0.011). Multivariate analysis showed that perioperative infections other than urinary tract infection remained a significant risk factor for decreased survival (progression-free survival, P = 0.02; and overall survival, P = 0.019). CONCLUSION: Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.
Assuntos
Cistadenocarcinoma Seroso/cirurgia , Neoplasias Ovarianas/cirurgia , Infecção da Ferida Cirúrgica/mortalidade , Infecções Urinárias/complicações , Área Sob a Curva , Bacteroides fragilis/isolamento & purificação , Baltimore , Cistadenocarcinoma Seroso/complicações , Cistadenocarcinoma Seroso/mortalidade , Intervalo Livre de Doença , Enterococcus/isolamento & purificação , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella pneumoniae/isolamento & purificação , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/mortalidade , Período Perioperatório , Análise de Regressão , Fatores de Risco , Análise de SobrevidaRESUMO
OBJECTIVE: While the development of an index of clinical symptoms to use for the detection and diagnosis of ovarian cancer is under active investigation, the role of clinical symptoms in survival after the initial diagnosis is poorly understood. The aim of this study was to correlate the type and extent of clinical symptoms with survival outcomes in ovarian cancer. METHODS: Medical records of 276 cases of primary epithelial ovarian, fallopian tube, and peritoneal cancers were evaluated. Thirty-one symptoms in 5 categories were cataloged. The significance of clinical symptoms in progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Overall, 93.5% of ovarian cancer patients expressed at least 1 symptom at the time of initial diagnosis. The 3 most common symptoms were abdominal pain (40.6%), increased abdominal size (33.7%), and bloating (21.7%). In survival analysis, weight loss (16.3%), nausea/vomiting (13.4%), and lower extremity edema (6.5%) were significantly associated with both decreased PFS and OS (all, P < 0.05). In multivariate analysis, lower extremity edema remained the strongest significant symptom, associated with increased surgical mortality rate, decreased response rate to adjuvant chemotherapy after primary cytoreductive surgery, and diminished survival outcomes (median PFS, 4.9 vs 15.3 months, P < 0.0001; and median OS, 5.9 vs 49.1 months, P < 0.001). Multiple symptoms were associated with poor survival outcomes (individual number of symptom ≤1 vs 2 vs ≥3; median PFS, 26.8 vs 17.4 vs 11.7 months [P < 0.001]; and median OS, 70 vs 41.6 vs 37.2 months [P < 0.001]). CONCLUSIONS: Lower extremity edema at initial diagnosis is a strong prognostic indicator of ovarian cancer patient.
Assuntos
Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Ovarianas/diagnóstico , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Taxa de SobrevidaRESUMO
OBJECTIVE: The objective of this study was to evaluate the clinical significance of the extent of extreme drug resistance (EDR) in in vitro drug resistance assays in advanced epithelial ovarian, fallopian, and primary peritoneal cancers. METHODS: A retrospective study was conducted using the database for in vitro drug resistance assay (EDR Assay, Oncotech, Inc.) results for advanced stage ovarian cancer samples obtained at primary surgery between 1995 and 2009. In vitro drug resistance assay results were evaluated for thirteen drugs according to the following two groups: platinum and taxane (primary treatment group) vs remaining agents (secondary treatment group). Dual-resistance was then defined as at least one EDR in the primary and secondary treatment groups. Chemotherapy response and survival outcome were correlated with assay results. RESULTS: There were 253 cases identified. Dual-resistance (n=53, 20.9%) was not associated with chemotherapy response (p=0.62) or survival outcomes (PFS, p=0.52; OS, p=0.11). Only one (0.4%) case exhibited complete EDR to all tested drugs, and 74 (29.4%) cases showed no EDR. There was no statistical correlation between total number of drugs in the EDR range and chemotherapy response (p=0.55), progression-free survival (PFS) (p=0.18), and overall survival (OS) (p=0.87). Proportion of EDR, defined as the ratio of the number of EDR drugs divided by all drugs for an individual patient, was also not related to chemotherapy response (p=0.37), PFS (p=0.13), or OS (p=0.13). CONCLUSIONS: Presence of extreme drug resistance to multiple agents in the in vitro drug resistance assays was not associated with survival outcomes in advanced stage epithelial ovarian, fallopian, and primary peritoneal cancers.
Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Bases de Dados Factuais , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células Epiteliais/patologia , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate drug resistance after exposure to neoadjuvant chemotherapy and to postoperative chemotherapy in epithelial ovarian, fallopian, and primary peritoneal carcinomas. METHODS: In vitro drug resistance assay results (EDR Assay, Oncotech, Inc.) for platinum and taxane were evaluated for the following three groups: (1) primary cytoreductive surgery without prior chemotherapy; (2) primary cytoreductive surgery after neoadjuvant chemotherapy with platinum and taxane; and (3) recurrent cases after postoperative chemotherapy with platinum and taxane. Proportions of extreme drug resistance (EDR) were analyzed with Fisher's exact test. RESULTS: There were 277 cases that underwent primary cytoreductive surgery without prior chemotherapy: 14 cases of primary cytoreductive surgery after neoadjuvant chemotherapy with platinum and taxane, and 65 recurrent cases. Primary cytoreductive cases following neoadjuvant chemotherapy displayed an increased proportion of EDR to platinum agents compared to primary cytoreductive surgery without prior chemotherapy: neoadjuvant versus non-neoadjuvant, cisplatin 30 versus 7.3%, OR 5.4, 95%CI 1.3-23.2, P=0.027; carboplatin 33.3 versus 9.2%, OR 4.9, 95%CI 1.4-17.6, P=0.038. There were no differences in the proportion of EDR to taxanes between the two groups. On the contrary, recurrent cases showed an increased proportion of EDR to paclitaxel compared to primary cytoreductive surgery without prior chemotherapy: recurrent versus primary, paclitaxel 33.3 versus 21.1%, OR 1.9, 95%CI 1.0-3.5, P=0.031. There were no differences in the proportion of EDR for platinum and docetaxel between the two groups. Among recurrent cases, there was statistical significance between proportion of paclitaxel EDR and time interval of initial and recurrent surgeries (R2 0.143, P=0.011). Recurrent surgery after 5 years from initial cytoreduction was significantly associated with increased proportion of EDR to paclitaxel: 61.5 versus 22.6%, OR 5.5, 95%CI 1.35-22.2, P=0.011. CONCLUSIONS: Platinum resistance was common after neoadjuvant chemotherapy, while paclitaxel resistance was common after postoperative chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/uso terapêutico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Taxoides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estudos Retrospectivos , Taxoides/administração & dosagem , Fatores de TempoRESUMO
The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression-free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5-year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5-year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p < 0.001). In conclusion, LDR to both platinum and taxane chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bioensaio/métodos , Resistencia a Medicamentos Antineoplásicos , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/secundário , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/secundário , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Técnicas In Vitro , Metástase Linfática , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
BACKGROUND: Rectovaginal fistula in long-standing Crohn's disease is possibly associated with malignant transformation to mucinous adenocarcinoma of the vagina. However, there have been no previously reported cases documenting vulvar cancer in association with rectovaginal fistula in Crohn's disease. We report 2 cases of vulvar mucinous adenocarcinoma associated with Crohn's disease. Both showed vulvar symptoms after the development of rectovaginal fistula. CASE 1: A 48-year-old woman, with a 30-year history of Crohn's disease including a rectovaginal fistula, developed persistent pyoderma gangrenosum. Further workup revealed metastatic vulvar mucinous adenocarcinoma. CASE 2: A 37-year-old woman with long-standing Crohn's disease including numerous episodes of perianal or rectovaginal fistulas complained of a vulvar mass suspicious for an abscess. Biopsy showed mucinous adenocarcinoma. CONCLUSION: Vulvar lesions or symptoms in the setting of rectovaginal fistula in Crohn's disease are an important clinical feature and the possible development of vulvar cancer should be considered.
Assuntos
Adenocarcinoma Mucinoso/etiologia , Doença de Crohn/complicações , Fístula Retovaginal/complicações , Neoplasias Vulvares/etiologia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Tomografia por Emissão de Pósitrons , Neoplasias Vulvares/patologia , Neoplasias Vulvares/terapiaRESUMO
Retroperitoneal cyst is an extremely rare complication of pregnancy. The management of this rare clinical entity is not well understood. An 18-year-old primigravid woman at 11 weeks of gestation with twins presented with complaints of severe nausea and vomiting. Abdominal magnetic resonance imaging showed a 25 x 18 x 10-cm retroperitoneal cyst reaching up to the level of xiphoid processes. No solid component or ascites was seen. She underwent ultrasound-guided percutaneous aspiration of the cyst and 2 L of fluid was removed. The cytology was negative for malignant cells. There was no recurrence of retroperitoneal cyst during the subsequent pregnancy. At 37 (0)/ (7) weeks' gestation, the patient spontaneously delivered the female fetuses in cephalic and breech presentation. There were only seven cases reported in the literature of retroperitoneal cysts during pregnancy between 1955 and 2008. Retroperitoneal cyst during pregnancy is characterized by its extremely rare incidence and its massive cyst size. Because of the difficulty in surgery due to the gravid uterus and close proximity to major organs and blood vessels, percutaneous aspiration of cyst could be an option during pregnancy.
Assuntos
Cistos/diagnóstico por imagem , Complicações na Gravidez/terapia , Espaço Retroperitoneal/diagnóstico por imagem , Adolescente , Líquido Cístico/diagnóstico por imagem , Drenagem , Feminino , Humanos , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Espaço Retroperitoneal/patologia , Índice de Gravidade de Doença , UltrassonografiaRESUMO
We conducted a literature review to determine the clinical characteristics of genital sarcoma during pregnancy. The systematic literature search was conducted using the search engines PubMed and MEDLINE with keywords "sarcoma" and "pregnancy" and was limited to female genital organs such as ovary, uterus, cervix, vagina, vulva, and retroperitoneal sarcoma. Kaposi's sarcoma, metastatic sarcoma, history of sarcoma, bone sarcoma located in pelvis, and fetal sarcoma were excluded in this study. There were 40 cases of genital sarcoma during pregnancy between 1955 and 2007. The majority of the cases were uterine sarcoma (37.5%), followed by retroperitoneal sarcoma (27.5%), vulvar sarcoma (22.5%), and vaginal sarcoma (12.5%). Mean age of the patient was 27.8 +/- 7.0. The distribution in the onset of symptoms had two peaks: first trimester (27.5%) and third trimester (50.0%). Growing mass (42.5%), abdominal pain (30.0%), and vaginal bleeding (22.5%) were the three most common symptoms. Incidental diagnosis was made in 22.5% and included during cesarean section (12.5%) and routine pelvic exam (7.5%). The cases initially not suspicious for malignancy were 42.5%. Thirty-three (82.5%) cases had live-born infants with term delivery in 55.2%. Mean birth weight was 2843 +/- 791 g, and male infants were more common (66.7%). Intrauterine growth retardation was seen in 12.5% of cases. Preterm labor was a common complication. Median survival period was 2.5 years (95% confidence, 1.9 to 3.1). The 2-, 3-, and 5-year cumulative survival rates were 60%, 38%, and 17%, respectively. Genital sarcomas in pregnancy are rare. There is a delay in diagnosis due to low index of suspicion. A majority had live births, and the 5-year survival is similar to that of advanced-stage sarcoma in nonpregnant women.
Assuntos
Neoplasias dos Genitais Femininos/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Resultado da Gravidez , Diagnóstico Pré-Natal , Sarcoma/diagnóstico , Adulto , Cesárea , Terapia Combinada , Feminino , Neoplasias dos Genitais Femininos/mortalidade , Neoplasias dos Genitais Femininos/terapia , Humanos , Estadiamento de Neoplasias , Gravidez , Complicações Neoplásicas na Gravidez/mortalidade , Complicações Neoplásicas na Gravidez/terapia , Trimestres da Gravidez , Nascimento Prematuro , Prognóstico , Medição de Risco , Sarcoma/mortalidade , Sarcoma/terapia , Análise de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Endometriosis-associated ovarian cancer arising from the surgical incision site is an unusual clinical entity. CASE: A 37-year-old woman presented with a chief complaint of progressive swelling of the mons pubis. The patient was status post laparotomy for endometrioma/endometriosis 10 years ago. MRI showed a heterogeneous multiseptated large cystic mass within the mons pubis measuring 14 x 13.4 x 10.6 cm. Initial cytoreductive surgery revealed no evidence of tumor in the peritoneal cavity. The surgery was suboptimal due to severe adhesions to the symphysis pubis. The secondary cytoreductive surgery performed after six cycles of taxotere and carboplatin was optimal. Macroscopically, the tumor was a dusky pink-purple and contained a dense white-gray to light yellow gelatinous area. The tumor was a malignant cystic and glandular neoplasm. Immunohistochemical stains included CK7(+), CK5/6(-), EMA(+), Ber-Ep4(+), Calretinin(-), ER(-), and PR(-). CONCLUSION: Primary peritoneal clear cell adenocarcinoma arising from an abdominal scar associated with prior endometrioma/endometriosis surgery was first reported.
Assuntos
Adenocarcinoma de Células Claras/etiologia , Cicatriz/complicações , Endometriose/complicações , Neoplasias Peritoneais/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Endometriose/cirurgia , Feminino , HumanosRESUMO
OBJECTIVE: To examine clinico-pathological characteristics and outcomes of uterine carcinosarcoma (UCS) in women aged ≥80 years. METHODS: This is a secondary analysis of a previous multicenter retrospective study examining 906 women with stage I-IV UCS who underwent primary hysterectomy. Patient demographics, treatment types, tumor characteristics, and survival were examined across aged ≥80 (nâ¯=â¯82 [9.1%]), aged 60-79, (nâ¯=â¯526 [58.1%]), and aged <60 (nâ¯=â¯298 [32.9%]). RESULTS: Women in the aged ≥80 group were more likely to be Caucasian, undergo simple hysterectomy without lymphadenectomy, and receive no postoperative therapy (all, Pâ¯<â¯0.05). Tumors in the aged ≥80 group were more likely to have high-grade carcinoma, heterologous sarcoma, and sarcoma dominance but less likely to have lympho-vascular space invasion (all, Pâ¯<â¯0.05). Lymphadenectomy did not improve survival in the aged ≥80 group (Pâ¯>â¯0.05), whereas lymphadenectomy was protective for survival in the younger groups (both, Pâ¯<â¯0.05). Postoperative chemotherapy was associated with improved progression-free survival (PFS) in the aged ≥80 group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.89, Pâ¯=â¯0.021). With chemotherapy treatment, women in the aged ≥80 group had PFS similar to those in the aged 60-79 group (HR 0.97, 95%CI 0.51-1.83, Pâ¯=â¯0.92). In contrast, without chemotherapy treatment, women in the aged ≥80 group had significantly decreased PFS compared to the aged 60-79 group (HR 1.62, 95%CI 1.09-2.40, Pâ¯=â¯0.016). Similar associations were observed for postoperative radiotherapy. CONCLUSION: Nearly 10% of women with UCS are aged ≥80 that are characterized by aggressive tumor factors. Postoperative therapy but not extensive surgery may improve survival in this age group.
Assuntos
Carcinossarcoma/patologia , Quimioterapia Adjuvante/mortalidade , Histerectomia/mortalidade , Excisão de Linfonodo/mortalidade , Radioterapia Adjuvante/mortalidade , Neoplasias Uterinas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/mortalidade , Carcinossarcoma/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/terapiaRESUMO
BACKGROUND: Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. METHODS: In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. RESULTS: We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. CONCLUSION: In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis.