Câncer colorretal: associação entre variáveis sociodemográficas e a adesão a programas de rastreamento / Colorectal cancer: association between sociodemographic variables and the adherence to cancer screening

ABSTRACT BACKGROUND Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

RESUMO RACIONAL: O câncer colorretal (CCR) é um problema de saúde mundial cujo controle depende do estabelecimento de políticas públicas e programas de prevenção e rastreamento eficazes. No Brasil existem poucos estudos relacionados à adesão métodos de rastreamento. OBJETIVO: Avaliar a associação de características sócio-demográficas à realização de testes de sangue oculto nas fezes do tipo imunoquimicomecanizado (FIM) em população de médio risco para o desenvolvimento de câncer colorretal. MÉTODOS: Estudo observacional transversal, com coleta prospectiva de dados. Entre março de 2015 e abril de 2016, 1.254 indivíduos assintomáticos, com idade entre 50 e 75 anos, foram consecutivamente selecionados a partir de uma campanha hospitalar de rastreamento para neoplasias. RESULTADOS: As taxas de adesão ao teste FIM foi 55.6% (697/1254). Na análise de regressão logística múltipla os fatores independentes associados à adesão ao rastreamento do CCR foram: Idade entre 60-75 anos (oddsratio (OR)=1.30; intervalo de confiança de 95% (IC): 1.02-1.66; p=0.03), crença religiosa (OR=2.04; 95%IC: 1.34-3.11; p<0.01), realização prévia de exame de sangue oculto nas fezes (OR=2.07; 95%IC: 1.55-2.76; p<0.01) e vínculo empregatício em período integral ou parcial (OR=0.66; 95%IC: 0.49-0.89; p<0.01). CONCLUSÃO: Este estudo enfatiza a importância de considerar aspectos laborais ao implementar programas de rastreamento do câncer colorretal e sugere que campanhas de rastreamento implantadas no ambiente de trabalho e de maneira repetida ao longo dos anos podem ser mais efetivas.

É o carcinoma colônico localmente avançado não metastático uma variante biológica distinta? Estudo baseado na avaliação histológica, painel imuno-histoquímico e sobrevida / Is the non-metastatic, locally advanced colon adenocarinoma a distinct biological tumor variant? A study based on pathological evaluation, immunohistochemical panel and survival

RESUMO Objetivo: avaliar diferenças clínicas e patológicas entre os adenocarcinomas colônicos localmente avançados com aderências entre órgãos ou estruturas adjacentes (LACA) e adenocarcinomas colônicos com outras apresentações clínicas. Métodos: estudo retrospectivo a partir de amostra de conveniência de pacientes com adenocarcinoma colônico, estádio patológico pT3, distribuídos de acordo com características clínicas e patológicas em três grupos: tumores localmente avançados (LACA), tumores pT3 sem aderências ou metástases à distância (SF), e tumores com doença metastática (M1). Foram avaliadas as características clínicas e patológicas, e a expressão de sete marcadores imuno-histoquímicos relacionados à proliferação/apoptose, invasão celular/migração e metástase. Resultados: foram avaliados 101 pacientes: 30 LACA, 44 SF e 27 M1. Tumores localmente avançados apresentaram dimensões maiores e estiveram associados a aumento das taxas de infiltração linfocitária, menores níveis de expressão de bax e de CD 44v6 quando comparados aos grupos SF e M1. Diferenças significantes foram observadas em relação aos LACA e M1 em relação à localização colônica, histologia, estado linfonodal e expressão bax e CD44v6. Diferenças foram observadas em relação aos três grupos frente ao tamanho do tumor e infiltrado linfocítico. A sobrevida foi similar entre os grupos LACA e SF (p=0,66) e foi inferior no grupo M1 (p<0,001). Conclusão: os dados sugerem que os adenocarcinomas colônicos localmente avançados com aderências entre órgãos ou estruturas adjacentes representam uma entidade distinta.

ABSTRACT Objective: to evaluate the clinical and pathological differences between locally advanced colonic adenocarcinomas (LACA) with adhesions between adjacent organs or structures, and colonic adenocarcinomas with other clinical presentations. Methods: we conducted a retrospective study from a convenience sample of patients with colonic adenocarcinoma, pathological stage pT3, distributed according to clinical and pathological characteristics in three groups: locally advanced tumors (LACA), pT3 tumors without adhesions or distant metastases (SF) and tumors with metastatic disease (M1). We evaluated clinical and pathological characteristics and the expression of seven immunohistochemical markers related to proliferation/apoptosis, cell invasion/migration and metastasis. Results: we studied 101 patients: 30 LACA, 44 SF and 27 M1. Locally advanced tumors presented larger dimensions and were associated with increased lymphocyte infiltration rates, lower levels of bax expression, and CD 44v6 when compared with SF and M1 groups. We observed significant differences between LACA and M1 in relation to colonic location, histology, lymph node status and bax and CD44v6 expression. We found differences were observed between the three groups for tumor size and lymphocytic infiltrate. Survival was similar in the LACA and SF groups (p=0.66) and was lower in the M1 group (p<0.001). Conclusion: the data suggest that locally advanced colonic adenocarcinomas with adhesions between adjacent organs or structures represent a distinct entity.

Comparison between an immunochemical fecal occult blood test and a Guaiac based fecal occult blood test in detection of adenomas and colorectal cancer

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Brazil does not have an official well established program for screening colorectal cancer. The aim of this study was to compare Guaiac Based Fecal Occult Blood Test (G-FOBT) to a kind of an Immunochemical Fecal Occult Blood Test (I-FOBT), in search of cancer or advanced adenoma. Methods: Prospective and cross-sectional study. Asymptomatic and average-risk individuals (n = 1500) aged from 50 to 75 years old were invited to participate in the study. The primary endpoint was positivity rate and the secondary endpoints were adherence rate and significant endoscopic findings. All participants received both tests with follow-up colonoscopy if either test was positive. Results: Adherence rate of G- FOBT was 756/1500 (50.4%) while for I- FOBT it was 960/1500(64%). The positivity ratio in the I- FOBT was 94/960 (9.8%) and in the G-FOBT was 20/771 (2.6%). The Positive Predict Value (PPV) for the I- FOBT counted 16/77 (21.0%) while for the G- FOBT it was 6/18 (33.0%), considering significant lesions. Regarding the colorectal cancer findings, the detection in the colonoscopy guided from the positivity of fecal occult blood tests was 5/77 (6.5%) in I- FOBT and 2/18 (11.1%) on the G- FOBT. Conclusions: The positivity, the adherence rate and the capacity to detect significant lesions were higher in I-FOBT. Considering the findings of the study we could conclude that I-FOBT was superior to G- FOBT. Trial registration: This study was reviewed and approved by the Institutional Review Board of A.C.Camargo Cancer Center, São Paulo, Brazil, number: 1877/14

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08­6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients (AU)

Surgical complications and metachronous rectal cancer risk in patients with classic familial adenomatous polyposis / Complicações cirúrgicas e risco de câncer retal metacrônico em pacientes com polipose adenomatosa familiar clássica

INTRODUCTION: Familial adenomatous polyposis (FAP), an autosomal dominant disease characterized by development of numerous adenomatous polyps in the colon and rectum, is caused by germline mutations in the Adenomatous Polyposis Coli (APC) gene. METHODS: To determine the surgical morbidity in patients with classical familial adenomatous polyposis and determine the incidence of metachronous colorectal cancer (CRC) in those undergoing total colectomy (TC) with ileorectal anastomosis or restorative total proctocolectomy (TPC) and ileal pouch anal anastomosis. We analyzed patients with familial adenomatous polyposis who received treatment and regular follow-up at the A.C. Camargo Cancer Center from 1994 to 2013. RESULTS: Operative complications occurred in 22 patients (34.3%), 16 (25%) being early complications and 8 (12.5%) late complications. No mortality occurred as a result of postoperative complications. The incidence of metachronous rectal cancer after total proctocolectomy was 2.3% and after total colectomy 18.18% (p = 0.044). CONCLUSIONS: In order to provide better quality of life for individuals with familial adenomatous polyposis, total colectomy is commonly offered, as this simple technique is traditionally associated with lower rates of postoperative complications and better functional outcomes. However, it has become a less attractive technique in patients with familial adenomatous polyposis in its classical or diffuse form, since it has a significantly higher probability of metachronous rectal cancer. (AU)

INTRODUÇÃO: Polipose adenomatosa familiar (PAF), uma doença autossômica dominante caracterizada pela formação de numerosos pólipos adenomatosos no cólon e reto, é causada por mutações da linha germinativa no gene da polipose adenomatosa do cólon (PAC). MÉTODOS: Para determinar a morbidade cirúrgica em pacientes com PAF clássica e determinar a incidência de câncer colorretal (CCR) metacrônico naqueles pacientes submetidos à colectomia total (CT) com anastomose íleo-retal ou submetidos à proctocolectomia restaurativa (PCT) e anastomose bolsa ileal-anal, foram analisados pacientes com PAF que foram tratados e tiveram acompanhamento periódico no A. C. Camargo Cancer Center de 1994 até 2013. RESULTADOS: Ocorreram complicações cirúrgicas em 22 pacientes (34,3%); 16 (25%) tiveram complicações precoces e 8 (12,5%) complicações tardias. Não houve mortes como resultado de complicações pós-operatórias. A incidência de câncer de reto metacrônico após PCT foi de 2,3% e após CT foi de 18,18% (p = 0,044). CONCLUSÕES: A fim de proporcionar melhor qualidade de vida para os pacientes com PAF, CT é comumente oferecida, pois esta técnica simples está tradicionalmente associada com menores percentuais de complicações pós-operatórias e melhores resultados funcionais. No entanto, CT se tornou uma técnica menos atraente em pacientes com PAF em sua forma clássica ou difusa, uma vez que traz consigo uma probabilidade significativamente maior de câncer retal metacrônico. (AU)

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.

Correlação clínico molecular em pacientes portadores de câncer pertencente a famílias com suspeita de Síndrome de Lynch / Clinical molecular correlation in patients with cancer related to a Lynch Syndrome suspected families

Introdução - A Síndrome de Lynch é uma doença hereditária que predispõe aos tumores colorretais, entre outros tumores, em idade precoce, com padrão de herança autossômica dominante, representando a principal causa de hereditária de câncer intestinal. Os genes de reparo defeituosos são responsáveis pela síndrome e podem ser identificados através dos testes de seqüenciamento dos genes. Os genes MLH1 e MSH2 são responsáveis por mais de 85% das mutações germinativas encontradas nestas famílias. O restante são causadas por outros genes de menor incidência, MSH6 e PMS2. A correlação clínico-molecular foi avaliada mais extensivamente em populações norte-americanas, com poucos estudos com a população brasileira. Objetivos - Este estudo tem como objetivo avaliar a correlação clínico-molecular de dados referentes aos pacientes com suspeita de SL, assim como de dados de membros da família com câncer relacionados à síndrome. Materiais e métodos – foram estudados 43 pacientes probandos e os familiares selecionados a partir de casuística do Hospital A.C. Camargo que preenchiam os critérios clínicos para SL, Amsterdam I ou II e também pacientes com critérios de Bethesda que apresentassem mutação em qualquer dos genes de reparo. Todos os pacientes foram submetidos a pesquisa de mutações, por seqüenciamento direto, nos genes MLH1 e MSH2 e nos casos inconclusivos foram avaliados também para os genes MSH6 e PMS2. As variáveis clínicas, anatomopatológicas e dados familiares foram correlacionados com as informações obtidas dos estudos moleculares. Para a averiguação de associações entre variáveis foi realizada análise univariada, através do teste qui-quadrado ou exato de Fisher, e a sobrevida dos pacientes probandos através do método de Kaplan-Meier. Resultados - A freqüência de identificação de mutação patogênica nos genes de reparo foi de 60,2%, em 26 probandos...

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...

Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy in the Treatment of Peritoneal Dissemination of Neoplasias: Preliminary Results with Closed Perfusion Technique

OBJECTIVE: to describe preliminary results ofcytoreductive surgery and intraperitoneal hyperthermicchemotherapy in the treatment of peritonealcarcinomatosis from a brazilian single institution.MATERIALS AND METHODS: a short cohort study wascarried out. 26 patients and 28 procedures wereperformed consecutively between March 2001 and June2005. 17 patients (65.4%) were treated for pseudomyxomaperitonei, 4 patients had mesothelioma, 2 carcinomatosisfrom colorectal cancer origin, 2 from ovary cancer and 1had peritoneal sarcomatosis. All cases were treated withclosed perfusion technique. The Completeness ofCytoreduction Score was used to classify the radicalityof the procedure and the NIH Commom Toxicity Criteriawas used to classify the complications. RESULTS: CC0and CC1 resections were achieved in 24 cases (85.7%).Grade 3 or 4 toxicity were observed in 5 cases (17.8%)and two patients died (7.1%). Severe complications weresignificant associated with the duration of surgery (morethan 10 hours). CONCLUSION: this radical treatment ofperitoneal carcinomatosis envolves high morbidity andmortality rates and must be conducted in referral centerswith multiprofessional teams and carefully selection ofpatients.

Clinicopathological Significance of BAT26Instability in 184 Patients with Colorectal Cancer

Microsatellite instability (MSI) occurs in 90% ofcolorectal cancer (CRC) from HNPCC patients and 15%of sporadic CRC. Patients with CRC and MSI have adistinct phenotype. OBJECTIVE: this study evaluates theisolated clinicopathological significance of BAT26instability by itself in patients with CRC. METHODS:From 1995 to 2000, 184 patients submitted to CRC surgerywere selected at random. Medical records were studiedin order to determine clinical data and BAT26 analysiswas carried out. RESULTS: BAT26 instability was foundin 22 (12%) of the 184 cases and was correlated to proximalcolon tumors (p<0.001); CRC from HNPCC patients(p=0.002); poor cell differentiation (p=0,025); andmucinous component (p=0,007). BAT26 instabilitytumors have shown a slight trend toward absence ofmetastases (p=0,082). The five-year cancer-specificsurvival was 65% and 85% for stable and instable BAT26,respectively, with no statistical significance.CONCLUSION: BAT26 instability should be considereda useful screening method to select CRC patients forMSI.