Disparidades na mortalidade de câncer colorretal nos estados brasileiros / Disparities in colorectal cancer mortality across Brazilian States

RESUMO: Objetivo: Analisar a tendência da mortalidade por câncer colorretal, ajustado por indicadores selecionados, segundo sexo, para unidades federativas, regiões e Brasil, no período de 1996 a 2012. Métodos: Estudo ecológico de série temporal das taxas de mortalidade por câncer colorretal, feita análise de regressão linear, sendo o ano centralizado a variável independente. Os modelos foram ajustados por indicadores selecionados. Resultados: Houve aumento nas taxas de mortalidade padronizadas por câncer colorretal em todos os estados para o sexo masculino e em 21 estados para o sexo feminino. No modelo ajustado por taxa de mortalidade por causas mal definidas, produto interno bruto e coeficiente de Gini, a tendência de aumento foi significativa (p < 0,05) no Brasil, somente para os homens, com 0,17 óbitos por 100 mil habitantes ao ano (aa). Nos estados do Piauí (0,09 e 0,20 aa), Ceará (0,17 e 0,19 aa) e Rio Grande do Sul (0,61 e 0,42 aa) ocorreu aumento em homens e mulheres, respectivamente; somente em homens nos estados da Paraíba (0,16 aa), no Espírito Santo (0,28 aa), em São Paulo (0,24 aa) e Goiás (0,31 aa); e em mulheres nos estados de Roraima (0,41 aa), do Amapá (0,97 aa), Maranhão (0,10 aa), Sergipe (0,46 aa), Mato Grosso do Sul (0,47 aa) e Distrito Federal (0,69 aa). Conclusão: O aumento da taxa de mortalidade por câncer colorretal manteve-se significativo no Brasil somente entre os homens; em sete estados, entre homens; e em nove estados, entre mulheres, independentemente dos indicadores estudados. Essas diferenças podem estar relacionadas ao possível aumento da incidência e ao acesso tardio ao diagnóstico e tratamento.

ABSTRACT: Objective: To analyze the trend of colorectal cancer mortality adjusted for selected indicators, according to sex, by Brazilian federative units and regions, and countrywide from 1996 to 2012. Methods: This is a temporal time series on colorectal cancer mortality rates, using linear regression analysis, in which the independent variable was the centered year. Models were adjusted for selected indicators. Results: There was an increase in standardized colorectal cancer mortality rates for males in all states and for females in 21 states. In the model adjusted for mortality rate from ill-defined causes, for gross domestic product, and for Gini coefficient, the upward trend remained statistically significant (p < 0.05) countrywide only for men, with 0.17 deaths per 100 thousand inhabitants per year (py). In the States of Piauí (0.09 and 0.20 py), Ceará (0.17 and 0.19 py) and Rio Grande do Sul (0.61 and 0.42 py), there was an increase for both men and women, respectively; only among men in the States of Paraíba (0.16 py), Espírito Santo (0.28 py), São Paulo (0.24 py) and Goiás (0.31 py); and among women in Roraima (0.41 py), Amapá (0.97 P/Y), Maranhão (0.10 py), Sergipe (0.46 P/Y), Mato Grosso do Sul (0.47 py), and the Federal District (0.69 py). Conclusion: The increase in colorectal cancer mortality remained significant when assessing Brazil as a whole only among men; in seven States among men, and in nine States among women, regardless of the studied indicators. These differences could be related to the possible increase in incidence and to late access to diagnosis and treatment.

Predictors of quality of life in colorectal cancer patients treated with curative intention

This study aims to evaluate predictors of quality of life in patients treated for colorectal cancer (CRC) with curative intention. PATIENT/METHODS: All patients with CRC treated with curative intention were interviewed by telephone using the SF-36 questionnaire.RESULTS/FINDINGS: One hundred and one patients (44 men, 57 women) were included in this study with a mean age of 60.8 years. Sixty-nine patients were treated for rectal cancer and 32 for colon cancer. Of the total, 23 patients had a stoma (22.8%) and 55 (54.5%) reported comorbidities. The means of the SF-36 scales varied between 90 (emotional aspects) and 65 (physical aspects). Presence of comorbidities was a predictor factor of quality of life in six of eight SF-36 scales. The female patients attained lower scores on three scales: functional capacity, pain and vitality. Patients age 60 or over attained lower scores on two SF-36 scales: functional capacity and social aspects. Patients with a stoma had lower score on limitation due to emotional aspects. We concluded that comorbidities affect the quality of life of individuals with colorectal cancer. Health professionals should be prepared to address not only the limitations caused by cancer and its treatment, but also the limitations caused by chronic diseases.

Câncer colorretal / Colorectal cancer

O câncer colorretal se destaca entre as neoplasias malignas mais incidentes no Brasil e no mundo. Estratégias de rastreamento incluem a pesquisa de sangue oculto nas fezes ou a colonoscopia, aplicadas às populações sob maior risco. A sintomatologia é pouco específica e a colonoscopia é o método ideal para diagnóstico, sendo indicada sempre que houver sinais e sintomas intestinais. O estadiamento define as modalidades de tratamento e é direcionado para as vias mais comuns da disseminação da doença: linfática, hematogênica, contiguidade e implantes. Quando o diagnóstico se faz em estádios iniciais, o tratamento do câncer colorretal proporciona elevadas taxas de cura. Este artigo resume de forma esquemática as modalidades atuais de tratamento, estratificadas em função do estadiamento.

Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5 percent, 46.7 percent and 58.3 percent, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3 percent and 41.2 percent, respectively. Severe wound complications were observed in 41.8 percent of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7 percent (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.

Mismatch repair genes in Lynch syndrome: a review: [review] / Genes de reparo de DNA na síndrome de Lynch: uma revisão: [revisão]

Lynch syndrome represents 1-7 percent of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50 percent) and MSH2 (40 percent), while others account for 10 percent. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

A síndrome de Lynch representa de 1-7 por cento de todos os casos de câncer colorretal. É uma síndrome de herança autossômica dominante que predispõe ao câncer e é causada por mutações nos genes de reparo de ácido desoxirribonucléico (DNA). Desde a descoberta dos principais genes com função de reparo de DNA, mutações nos genes MSH2, MLH1, MSH6, PMS2 e PMS1 estão relacionadas com a susceptibilidade à síndrome de Lynch. Outro gene, MLH3, tem sido proposto como tendo papel na predisposição à síndrome de Lynch, porém mutações de significância clínica nesse gene não são claras. De acordo com o banco de dados InSiGHT (International Society for Gastrointestinal Hereditary Tumors), aproximadamente 500 diferentes mutações associadas à síndrome de Lynch são conhecidas, envolvendo primeiramente MLH1 (50 por cento), MSH2 (40 por cento) e outros (10 por cento). Grandes progressos têm ocorrido para nosso entendimento das bases moleculares da síndrome de Lynch. A caracterização molecular será a forma mais precisa para definirmos a síndrome de Lynch e irá fornecer informações preditivas mais precisas sobre o risco de câncer colorretal e extra-colônico, além de permitir regimes otimizados de manejo.

Familial adenomatous polyposis: data from the Hereditary Colorectal Cancer Registry (HCCR)

Family adenomatous polyposis (FAP) is a dominant autossomic disease responsible for nearly 1% of colorectal cancer (CRC) cases caused by mutations in gene APC and nearly complete penetrance. The identification of germinative mutations can be useful in the definition of the therapeutic conduct by means of the correlation genotype-phenotype. Objective: To describe clinical and molecular characteristics of families with FAP or attenuated FAP. Method: The study included families registered in the Hereditary Colorectal Cancer Registry of A.C.Camargo Hospital. Cancer records were registered and heredograms were created. Data were collected and stored in a database. Results: From 1992 to 2007 22 families were registered that had FAP, 16 with classic FAP, nine with Gardner Syndrome, and 6 with attenuated FAP. From 604 individuals, 120 had polyposis, 62 CRC, 10 desmoid tumors, three breast tumors, two tumors of the stomach, two thyroid tumors and one with prostate tumor. From 22 families, three were submitted to molecular analysis and mutations were identified in gene APC. Discussion: Half of the individuals presented CRC concomitant to polyposis, which can indicate a late diagnostic of the disease; three identified mutations presented correlations genotype-phenotype as predicted by the literature. Follow-up of patients with FAP, although they account for less than 1% of CRC cases, is vital for early cancer diagnosis.

P16 and p27 Immunohistochemical Expression in Colorectal Cancer: Analysis of 128 Patients

P16 and p27 are inhibiting proteins of cyclin-dependent kinases (CDKIs) that act in the restriction points of the cellular cycle, and it avoids its progression to DNA verification and repair by the cellular apparatus. This way, there should be, physiologically, an inverse relation between the expression of these proteins and cellular proliferation. However, what is really observed are changeable amounts of p27 in normal and tumor tissues. P16 participation in tumorigenesis is controversial. The expression of p16 and p27 as a prognostic factor in colorectal cancer (CRC) patients is controversial. Objetive: To establish a correlation between p16 and p27 immunohistochemical expressions with clinical and anatomopathological variable from patients with CRC. Material and methods: descriptive and retrospective study, with 128 CRC patients, treated surgically between 2000 and 2004, with available material for immunohistochemical analysis through standardized methods. The association between categorical variables was done using Chi-square, Pearson or Fisher?s Exact tests, and the continuous variables were analyzed by t-Student. Global survival and disease-free period were calculated according to Kaplan-Meier method and the associations through log-rank test. Results: The average follow-up time of patients was 35 months. Positivity of p16 was detected in 100% of cases. Negativity of p27 in 6.3% (n=8) of cases, with a significant association (p30.05) between p27 negative and tumors located in right colon (62.5%, n=5) and mucinous (62.5%, n=5). The average global survival was 54.8 months, and the significant clinical and pathological variables associated to survival were: better for curative surgeries; better for early stages; better for well-differentiated tumors; worse for cases with sanguineous or vascular lymphatic invasion; worse for perineural invasion. Conclusions: p27 negative is more frequent in right colon...

p53 and p21 Immunohistochemistry in Colorectal Cancer: Clinical and Pathological Correlation in 128 Cases

Mutations of tumoral suppressor TP53 gene are present in 75% of colorectal cancer (CRC) cases. Immunohistochemistry isa method capable of demonstrating the abnormal accumulation of p53 protein in the cell. Some studies associate p53immunohistochemical positivity and a worse prognosis, while others do not confirm this finding. There are controversiesregarding the prognostic value of p53 in CRC. The same doubts apply to p21 protein, activated by p53, which is the mainresponsible for stopping the cell cycle (checkpoints), both for repair or apoptosis purposes. Objective: The objective of thisstudy is to correlate p53 and p21 immunohistochemical expression both with clinical and anatomopathological variables andwith survival rates of patients with CRC. Materials and Methods: This is a descriptive and retrospective study having asresearch subjects 128 patients affected by CRC and treated surgically from 2000 to 2004, with available surgical specimensfor immunohistochemical analysis using standardized methods. The association among categorical variables was done byPearson chi-square or Fisher exact tests, and the continuous variables were analyzed by t-Student test. Overall survival anddisease-free period rates had been calculated according to Kaplan-Meier method and the associations by log-rank test. Results:Follow-up average time was 35 months. p53 and p21 alterations had been detected, respectively, in 67.2% and 27. 3% ofcases, with a significant association (p<0.05) between p53 and tumors located in rectum (76.0%) and left colon (70.7%), andbetween p21 and right colon (43.2%). p21 positive expression was related to CRC diagnostic at an older median age. Overallsurvival was 54 months, and the significant clinical and pathological related variables were the following: better for curativesurgeries; better for precocious stages; better for well-differentiated tumors; worse for cases with sanguineous or lymphatic...

Number of Disected Lymph Nodes In Colorectal Cancer Patients SubmittedTo Radical Surgery: The Quality of Oncology Treatment

Introduction: the correct evaluation of lymph node disease influences the therapeutical decisions of colon and rectal cancer(CRC) patients. The number of dissected lymph nodes is a variable that have prognostic value and serves as an indicator of thequality of oncology treatment. For a correct evaluation of N stage to be accepted, the minimum number of dissected lymphnodes considered must be 12. In rectal cancer patients submitted to neoadjuvant radiochemotherapy, the interpretation of thenumber of dissected lymph nodes remains inconclusive. Objective: is to evaluate the number of dissected lymph nodes in CRCpatients submitted to curative surgery and determine this latter impact in oncologic treatment results. In cases of rectalcancer, to study the effect of neoadjuvant radiochemotherapy in dissected lymph nodes count. Method: in the period 1991-2004, 852 CRC patients were treated in Hospital A. C. Camargo . Patients with metastases at the time of diagnosis,synchronous and metachronic tumors, total colectomy or total proctocolectomy and hereditary colorectal cancer were excluded.The sample was constituted by 423 patients with sporadic colorectal adenocarcinoma who undergone curative radical surgery(168 colon primary tumors and 255 rectal tumors). Colon cancer patients, treated primarily by surgery, had also receivedadjuvant chemotherapy (5-FU) according to risk criteria. Rectal cancer patients with fixed or half-fixed injuries or clinicallycompromised lymph nodes (T3, T4 or N+) had received neoadjuvant radiochemotherapy, followed by surgery and chemotherapy(5-FU). Results: the median of the number of dissected lymph nodes in colon cancer patients was 17. In the case of rectalcancer patients, the median of dissected lymph nodes in the groups with and without neoadjuvant radiochemotherapy had beenrespectively 9 and 15 (p<0.001). 5-year specific survival rates for colon and rectal cancer patients were respectively...

Condrossarcoma de ramo púbico superior simulando hérnia inguinal / Chondrosarcoma of the superior pubic ramus simulating an inguinal hernia

Primary pelvic tumors are relatively rare, representing no more than 5 percent of primary bone tumors. We presented a case of a chondrosarcoma of the superior pubic ramus initially managed as an inguinal hernia and then operated under oncological principles. Special attention is attributed to the importance for the correct diagnosis and surgical treatment given the low efficacy of adjuvant treatments for this type of neoplasia.

Reconstruction of Urinary and Gastrointestinal Tracts in Patients Submitted to Pelvic Exenteration and Sphincter Preservation

Background and Objective: Reports in the literature regarding reconstruction of the lower urinary tract with orthotopic ilealneobladder post radical cystectomy for either non-transitional cell bladder tumors or other pelvic malignancies are rare. In suchcases, the reconstruction with orthotopic neobladder may represent a technical and therapeutic challenge, especially due topatients’ previous treatments like radiotherapy. To evaluate the feasibility and oncological results of the reconstruction ofurinary and gastrointestinal tracts in patients submitted to pelvic exenteration. Methods: From April 1995 to January 2004, 13patients with pelvic malignancies and non-transitional cell bladder tumors were submitted to pelvic exenteration. Bladderreconstruction was accomplished through orthotopic ileal neobladder in all cases. Seven patients had total pelvic exenterationwith anal sphincter-sparing procedure done as well as double-stapled colorectal anastomosis. Results: The mean age was 50years. In 6 patients late complications, such as hydronephrosis and urinary infection, were observed. No patient presented daytimeurinary incontinence after 6 months. During the follow-up period, no urethral recurrences were noted and all patientsremained with their functional neobladders. Two patients died of treatment-related causes and three died of cancer; sevenpatients are alive with no evidence of disease and one is alive with cancer. Overall and cancer-specific survival at 24 and 60months was 77.0% and 57%, respectively, and the mean of follow-up was 47% months (median 43 month). Conclusions:Urinary sphincter preservation and bladder reconstruction with orthotopic ileal neobladder with or without concomitant fecalsphincter preservation is a valuable option in patients with non-transitional cell bladder tumors or other pelvic malignancies thatrequire radical cystectomy for curative purposes.