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1.
J Surg Oncol ; 121(5): 730-742, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31845348

RESUMO

BACKGROUND: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS: The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS: It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.


Assuntos
Países em Desenvolvimento , Neoplasias do Endométrio/cirurgia , Acessibilidade aos Serviços de Saúde , Brasil , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Continuidade da Assistência ao Paciente , Diagnóstico por Imagem , Neoplasias do Endométrio/patologia , Feminino , Preservação da Fertilidade , Humanos , Histerectomia , Excisão de Linfonodo , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Exame Físico , Encaminhamento e Consulta , Biópsia de Linfonodo Sentinela , Sociedades Médicas
2.
Brachytherapy ; 17(6): 935-943, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30100273

RESUMO

PURPOSE: To identify if baseline patient or magnetic resonance imaging (MRI) features can predict which women are at risk for inadequate tumor coverage with only intracavitary tandem and ovoid (T + O) brachytherapy and to correlate tumor coverage with clinical outcomes. METHODS AND MATERIALS: We performed a retrospective study of 50 women with cervical cancer treated with chemoradiation at a single institution between January 2014 and December 2015. All patients had a 3T-MRI performed at baseline (MRI1) and at the completion of external beam radiation therapy (MRI2). Gross tumor volume initial (GTV-Tinit) was measured on MRI1 and high-risk clinical tissue volume (CTVHR) on MRI2. CTVHR extending beyond point A was classified as too large for adequate coverage with T + O and requiring interstitial needles. Multivariate analysis was performed to determine predictive factors of inadequate coverage. Kaplan-Meier and Cox Regression were performed to correlate inadequate coverage with outcomes. RESULTS: Mean patient age was 49.2 ± 13.2 years, and 84% had Federation of Gynecology and Obstetrics IIB/IIIB disease. Forty-two percent of women were estimated to have inadequate tumor coverage with T + O brachytherapy. The GTV-Tinit volume and dimensions (superior-inferior, left-right, anterior-posterior) on MRI1 were all important predictive factors of inadequate coverage on multivariate analysis. Receiver operating characteristics curves identified optimal thresholds of superior-inferior ≥ 4.5 cm (area under the curve [AUC] = 0.718), left-right ≥ 4.5 cm (AUC = 0.745), anterior-posterior ≥ 5.0 cm (AUC = 0.767), and GTV-Tinit ≥ 85 cm3 (AUC = 0.842). Patients with inadequate coverage had worse clinical outcomes. CONCLUSIONS: Baseline MRI tumor size may predict inadequate CTVHR coverage at the time of brachytherapy (i.e., the need for interstitial needles). This may help identify a subset of women requiring early referral to adequately resourced centers to improve clinical outcomes.


Assuntos
Braquiterapia/métodos , Catéteres/estatística & dados numéricos , Quimiorradioterapia/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Área Sob a Curva , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Curva ROC , Dosagem Radioterapêutica , Estudos Retrospectivos , Medição de Risco/métodos
3.
PLoS One ; 10(12): e0144333, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26674523

RESUMO

OBJECTIVE: To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC). METHODS: This retrospective study included 114 patients with stage I-IV CRC who underwent primary tumour resection. Quantitative real-time PCR and immunohistochemistry assays were conducted using primary tumour samples. Kaplan-Meier survival curves were also generated to identify differences in global survival (GS) and disease-free survival (DFS) for the hypo- or hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise Cox regression models were also used to identify the risk factors associated with GS and DFS in a multivariate mode, and then were used to score the risk of death associated with each marker, either independently or in association. RESULTS: In the univariate analyses, significant differences in GS in relation to the expression profiles of ITGAV (p = 0.001), ITGA3 (p = 0.002), ITGA6 (p = 0.001), SPARC (p = 0.036), MMP9 (p = 0.034), and MMP16 (p = 0.038) were observed. For DFS, significant differences were observed in associated with ITGAV (p = 0.004) and ITGA3 (p = 0.001). However, only the ITGAV and ITGA6 gene markers for GS (hazard ratio (HR) = 3.209, 95% confidence interval (CI) = 1.412-7.293, p = 0.005 and HR = 3.105, 95% CI = 1.367-7.055, p = 0.007, respectively), and ITGA3 for DFS (HR = 3.806, 95% CI = 1.573-9.209, p = 0.003), remained in the final Cox regression models. A scoring system was developed to evaluate the risk of patient death based on the number of markers for the components of the final GS model. Scores of 0, 1, or 2 were associated with the following mean survival rates [CI]: 47.162 [44.613-49.711], 39.717 [35.471-43.964], 30.197 [24.030-36.327], respectively. CONCLUSIONS: Multivariate mathematical models demonstrated an association between hyperexpression of the ITGAV and ITGA6 integrins and GS, and also between the ITGA3 integrin and DFS, in patients with colorectal tumours. A risk scoring system based on detected hyperexpression of 0, 1, or 2 markers (e.g., ITGAV and/or ITGA6) was also found to accurately correlate with the GS curves generated for the present cohort.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Integrina alfa3/genética , Integrina alfa6/genética , Integrina alfaV/genética , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfa6/metabolismo , Integrina alfaV/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
4.
ScientificWorldJournal ; 2014: 102541, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24737953

RESUMO

Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry tissue microarray methods were performed in samples from the primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5 genes were overexpressed in tumors with lymph node and distant metastasis (III/IV-stage tumors compared with I/II tumors). The MMP-2 gene showed significant overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a significant expression correlation with EGFR epithelial marker. The overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in mucinous and villous adenocarcinoma type tumors, respectively. The epithelial marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9 and ITGA-3 expression.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Adulto Jovem
5.
Oncology ; 84(2): 81-91, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23128103

RESUMO

OBJECTIVE: To evaluate the relationship between the expression of the extracellular matrix (ECM) genes SPARC, SPP1, FN1, ITGA5 and ITGAV and the histopathologic parameters of neoplastic progression and colorectal carcinoma (CRC) dissemination. METHODS: A retrospective study was conducted in 114 patients with stage I-IV CRC who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry (IHC) assays were performed in samples obtained from the primary tumors. The correlation between the expression of these markers and the expression of p53, Bcl-2, Ki67, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor was assessed with the Spearman coefficient (r). RESULTS: The ITGAV gene was found to be significantly amplified in tumors with positive perineural invasion (p = 0.028). Expression of the SPARC, SPP1, FN1, ITGA5 and ITGAV genes did not correlate with TNM staging. A direct relationship between ITGAV and EGFR expression (r = 0.774; p < 0.001) was observed by IHC. CONCLUSIONS: ECM gene expression did not correlate with classical prognostic factors for CRC, but overexpression of the ITGAV gene and protein was correlated with an increased risk of perineural invasion. The relationship between ITGAV and EGFR expression suggests the possibility of crosstalk in this signal pathway.


Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Fibronectinas/metabolismo , Integrina alfa5/metabolismo , Integrina alfaV/metabolismo , Osteopontina/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Fibronectinas/genética , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Integrina alfa5/genética , Integrina alfaV/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Osteonectina , Osteopontina/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/secundário , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Proteínas Supressoras de Tumor/genética , Adulto Jovem
6.
Oncology ; 83(6): 346-53, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23006972

RESUMO

PURPOSE: To determine the rate of unavoidable adjuvant chemoradiation (RCTX) due to histologic results after radical surgery in patients with early cervical cancer. PATIENTS AND METHODS: Between May 2004 and July 2011, 448 consecutive patients diagnosed with invasive cervical cancer stage IA1 L1 to IIA underwent laparoscopic staging at the Department of Gynecology and Gynecologic Oncology at Charité Berlin. Only in patients without lymph node metastases (n = 394) on frozen section, radical operation was continued either by laparoscopic radical hysterectomy (n = 228) or by radical vaginal trachelectomy (n = 166). The decision for adjuvant RCTX was reached among the members of an interdisciplinary tumor board according to the presence of risk factors. The mean age of patients was 39 years. Squamous cell cancer was found in 62.5%, adenocarcinoma in 32.7%, adenosquamous cancer in 3.8% and others in 1% of patients. Adjuvant treatment was indicated if at least one category 1 risk factor (pN1, R1 or RX, parametrial involvement) and/or any combination of category 2 risk factors (lymphovascular space involvement (LVSI), hemovascular space involvement, grading 3, young age, deep stromal invasion, large tumor size) were present. RESULTS: In 39 of 394 patients (9.9%), adjuvant RCTX was recommended due to category 1 risk factors (n = 25/6.4%) and category 2 risk factors (n = 14/3.5%). Tumor-involved (R0) or unclear resection margins (RX) were present in 4 (1%) and 1 (0.3%), parametrial involvement in 12 (3%) and positive lymph nodes in 11 (2.8%) patients, respectively. Hemovascular involvement was found in 14 (3.5%), LVSI in 113 (28.7%) and grading 3 in 122 (31%) patients, respectively. CONCLUSION: Laparoscopic staging is a reliable tool to keep the rate of tri-modal (surgery + chemotherapy + radiotherapy) treatments in patients with cervical cancer stage I and IIA after radical surgery at 10%. This percentage should be used as benchmark for the quality of interdisciplinary treatment of patients diagnosed with cervical cancer.


Assuntos
Laparoscopia/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Feminino , Humanos , Histerectomia/métodos , Excisão de Linfonodo/métodos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Vagina/cirurgia , Adulto Jovem
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