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BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

BACKGROUND: Considering the high incidence of colorectal cancer (CRC) related deaths, many studies have investigated variables that can affect survival, with the aim of prolonging survival. The nutritional status can also be predict survival in patients with CRC. OBJECTIVE: The aim of the present study was to evaluate if BMI, %FAT, PhA, PG-SGA, adiponectin levels, and vitamin D levels are relevant to the characterization and differentiation of patients with advanced CRC and patients with a history of CRC. METHODS: The study was carried out by patients with advanced colorectal cancer (Group 1) and patients in follow-up after colorectal cancer treatment (Group 2). Nutritional status was assessed using the body mass index, body fat percentage, phase angle from bioelectrical impedance, Patient-Generated Subjective Global Assessment score. Adiponectin concentrations were determined using an enzyme-linked immunosorbent assay, and vitamin D levels were measured using high performance liquid chromatography. RESULTS: Groups 1 and 2 consisted of 23 and 27 patients, respectively. The body mass index, body fat percentage, phase angle, vitamin D and adiponectin levels were not significantly different between the groups. The mean Patient-Generated Subjective Global Assessment score was significantly higher in group 1 compared with group 2, and was significantly correlated with the long-term mortality risk. CONCLUSION: Among the nutritional status parameters, only the Patient-Generated Subjective Global Assessment score was significantly different between the groups and was an important predictor of survival in patients with advanced colorectal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

BACKGROUND: Worldwide, colorectal cancer (CRC) and gastric cancer (GC) are the third and the fifth most prevalent, respectively. Diarrhea is a common symptom in patients on chemotherapy or radiotherapy treatment and can reduce treatment tolerance. Surgical resections and chemotherapy change the intestinal microbiota that can lead to lactose intolerance, small intestinal bacterial overgrowth (SIBO). OBJECTIVE: The aim of the study was to evaluate the frequency of diarrhea in patients with CRC and GC on chemotherapy with SIBO or intolerance of lactose. METHODS: This is a descriptive and observational study with patients of both sexes, over 18 years old, in treatment in the Gastro-Oncology outpatient clinic of the Federal University of São Paulo. Patients with a confirmed diagnosis of CRC or GC during chemotherapy treatment were included. To detect bacterial overgrowth and lactose intolerance, breath hydrogen test with lactulose and lactose was done. Number and aspects of the evacuations and toxicity degree were collected. For the nutritional assessment, weight and height were performed to calculate the BMI. and the Patient Generated Subjective Global Assessment (PG-SGA). RESULTS: A total of 33 patients were included, 29 with CRC and 3 with GC. Most of them were male (57.57%), mean age of 60.03±10.01 years and in chemotherapy with fluoropyrimidine and oxaliplatin (54.5%). Diarrhea was present in 57.6% and 30.3% had toxicity grade 2. According to the BMI, 78.9% were eutrophics, obese or overweight, but according to PG-SGA, 84.9% had moderate or severe nutritional risk grade. Between patients, 45% had lactose intolerance and 9% SIBO. Diarrhea grade 2-3 was observed in 66.6% of patients with SIBO and 66.7% of that with lactose intolerance. No statistical difference was observed between patients with SIBO or lactose intolerance and grade of diarrhea. CONCLUSION: Diarrhea was a frequent symptom in chemotherapy patients with gastric or colorectal cancer independent of the presence of SIBO or lactose intolerance. Surgery and chemotherapy treatment impacted in the intestinal habit of patients. Diagnosis of other causes of diarrhea may contribute to a better tolerance to treatment and quality of life.

Background : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. Aim : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. Methods: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. Results : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. Conclusion : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available. RESUMO Racional: O II Consenso Brasileiro de Câncer Gástrico da Associação Brasileira de Câncer Gástrico ABCG (Parte 1) foi recentemente publicado. Nesta ocasião inúmeros especialistas que atuam no tratamento desta doença expressaram suas opiniões diante declarações apresentadas. Objetivo: Apresentar as Diretrizes da ABCG (Parte 2) quanto às indicações de tratamento cirúrgico, técnicas operatórias, extensão de ressecção e terapia combinada. Métodos: Para formulação destas diretrizes os autores realizaram extensa e atual revisão referente a cada declaração presente no II Consenso, utilizando as bases Medline/PubMed, Cochrane Library e SciELO, inicialmente com os seguintes descritores: câncer gástrico, gastrectomia, linfadenectomia, terapia combinada. Ainda, cada declaração foi classificada de acordo com o nível de evidência e grau de recomendação. Resultados: Das 43 declarações presentes neste estudo, 11 (25,6%) foram classificadas com nível de evidência A, 20 (46,5%) B e 12 (27,9%) C. Quanto ao grau de recomendação, 18 (41,9%) declarações obtiveram grau de recomendação 1, 14 (32,6%) 2a, 10 (23,3%) 2b e um (2,3%) 3. Conclusão: O complemento das diretrizes aqui presentes possibilita que cirurgiões e oncologistas que atuam no combate ao câncer gástrico possam oferecer o melhor tratamento possível, de acordo com as condições locais disponíveis.

Background: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. Aim: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. Methods: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers “fully agree” and “partially agree” was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. Results: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. Conclusion: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency. Radium Hospital Foundation (Oslo, Norway)

Purpose It has become crucial to translate scientific findings and to find ways by which to mobilize local resources to improve the quality and accessibility of cancer care in developing countries. This study seeks to provide insight into challenge through examining differences in clinician documentation of patients with cancer treated at a Brazilian Public University Hospital. Methods ASCO Quality Oncology Practice Initiative (QOPI) measures were used to examine the care provided in the departments of breast, colorectal, lymphoma, gynecology, and lung cancers. For this study, data from a representative sample of patients receiving chemotherapy in the previous month were extracted and quality of cancer care indicators examined. Results Certain elements of medical care were consistently and appropriately documented, including cancer diagnosis and stage, chemotherapy planning, administration, and summary. In general, considering the specific cancer management measures, patients received recommended care in accordance with recognized guidelines. Despite this, a number of important gaps in care were identified, including the assessment and treatment of pain, documentation of chemotherapy intention, symptom and toxicity management, patients’ psychosocial status, and provision of a treatment summary at care completion. Conclusion These findings are encouraging in terms of adherence to core treatment guidelines in cancer care in Brazil. However, results suggest important opportunities for improving care across a number of domains, many of which represent a challenge throughout both developing and developed countries. This study may also provide preliminary guidance for enhancing educational and training programs for professionals and students alike, to implement high-quality, comprehensive cancer care.

Aging patients with cancer have a higher risk of mortality and treatment-associated morbidity than younger patients. Nutrition status may play an important role in cancer mortality. We aimed to evaluate the survival time of elderly patients with colorectal cancer and its association with body mass index (BMI), the patient-generated subjective global assessment (PG-SGA), and phase angle (PA).BMI, PG-SGA, and PA were determined for all patients (n = 250) at first assessment.Seventy-one (28.4%) patients were in active oncologic treatment (group 1) and 179 (71.6%) were in remission (group 2). At the time of the analysis, 73 (29.2%) patients had died and 177 (70.8%) were censored. The mean (standard deviation) age was 70.9 (7.49) years; 17.2% were undernourished, 56% normal weight, and 26.8% were overweight. According to the PG-SGA, 35.2% of patients needed some nutrition intervention and 4.4% needed it urgently. The mean PA was 4.94 ± 1°. PG-SGA, tumor stage, and PA differed significantly ( P.001) between the groups; BMI did not ( P = .459). Severe malnutrition (PG-SGA C), compared with PG-SGA A, was associated with a relative hazard of death of 12.04 (95% confidence interval [CI], 3.43-42.19, P.001). PA5° was associated with better prognosis: a relative hazard of 0.456 (95% CI, 0.263-0.792; P.005).Among elderly patients with colorectal cancer, PA and PG-SGA were prognosis factors. PA5° was associated with best survival and PG-SGA C with worst survival.

The aim of this study was to correlate patients with gastrointestinal cancer, classified according to different stages of cancer cachexia (SCC) as proposed by Fearon, with nutritional assessment tools such as PG-SGA, phase angle (PA), and handgrip strength. One hundred one patients with a mean age of 61.8 ± 12.8 yr, with 58.4% being men were included. 32.6% were malnourished according to the body mass index (BMI). A severe or moderate malnutrition had been diagnosed in 63.3% when assessed using the PG-SGA, 60.4% had decreased handgrip strength, and 57.4% had lower grades of PA. Among the patients in the study, 26% did not have cachexia, 11% had precachexia, 56% cachexia, and 8% refractory cachexia. The PG-SGA, PA, and handgrip strength were associated with cachexia (P ≤ 0.001). An increased risk of death was found in patients with cachexia [RR: 9.1; confidence interval (CI) 95%: 0.1-90.2, P = 0.039], refractory cachexia (RR: 69.4, CI 95%: 4.5-1073.8, P = 0.002), and increased serum C-reactive protein (CRP) levels (P0.001). In conclusion, most of the patients with digestive system cancer had cachexia or refractory cachexia in the first nutritional assessment. Nutritional risk, as determined by PG-SGA, was correlated with PA and handgrip strength. High CRP levels, cachexia, and refractory cachexia were prognostic factors for cancer patients.

BACKGROUND AND OBJECTIVES The prognosis of colorectal cancer (CRC) has improved in the last decades, however, a lower overall survival persists in the elderly. The understanding of immunity changes in the elderly with CRC will allow the emergence of new treatments with higher response rates. 4-1BB and CD40L, an immune checkpoint stimulator, play an important role in T-cell responses and platelets. Our aim was to characterize the soluble levels of CD40L and 4-1BB in CRC elderly patients. METHODS A cross-sectional study was performed in 41 patients with CRC and 35 healthy elderly controls. Patients with CRC were divided into three groups according to staging: 13 patients with advanced tumor restricted to the organ (stages II); 16 patients with lymph node metastasis (stage III); and 12 patients with distant metastasis (stage IV). RESULTS There were higher levels of soluble s4-1BB and sCD40L in CRC elderly stage II patients when compared with healthy controls (P = .0009 and P

Colorectal cancer is a leading cause of cancer that may metastasize. KRAS gene sequence of exon 2 should be examined for identification of patients that can be treated with anti-EGFR. The aim of the present study was to evaluate the efficacy of high-resolution melting (HRM) to detect KRAS mutations in colorectal cancer (CRC) tumors. The exon 2 of KRAS was amplified from 47 adenocarcinoma CRC tissues. The tumors were subjected to high-resolution melt using quantitative PCR to identify wild-type and mutant subgroups. The results were compared to the mutations detected by next-generation sequences (NGS). The study included 47 patients, with a mean age of 62 years, of whom 24 patients were male. Most of the patients had stage II or stage III tumors. The mean melting temperatures for the wild-type and mutated group at exon 2 were 78.13˚C and 77.87˚C, respectively (P

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer worldwide. Early diagnostic methods using serum biomarkers are required. The study of omics, most recently lipidomics, has the purpose of analyzing lipids for a better understanding of human lipidoma. The evolution of mass spectrometry methods, such as MALDI-MS technology, has enabled the detection and identification of a wide variety of lipids with great potential to open new avenues for predictive and preventive medicine. OBJECTIVE: To determine the lipid profile of patients with colorectal cancer and polyps. METHODS: Patients with stage I-III CRC, adenomatous polyps and individuals with normal colonoscopy were selected. All patients underwent peripheral blood collection for lipid extraction. The samples were analyzed by MALDI-MS technique for lipid identification. STATISTICAL ANALYSIS: Univariate and multivariate (principal component analysis [PCA] and discriminant analysis by partial least squares [PLS-DA]) analyses workflows were applied to the dataset, using MetaboAnalyst 3.0 software. The ions were identified according to the class of lipids using the online database Lipid Maps (http://www.lipidmaps.org). RESULTS: We included 88 individuals, 40 with CRC, 12 with polyps and 32 controls. Boxplot analysis showed eight VIP ions in the three groups. Differences were observed between the cancer and control groups, as well as between cancer and polyp, but not between polyps and control. The polyketide (810.1) was the lipid represented in cancer and overrepresented in polyp and control. Among the patients with CRC we observed differences between lipids with lymph node invasion (N1-2) compared to those without lymph node invasion (N). CONCLUSION: Possible lipid biomarkers were identified among cancer patients compared to control and polyp groups. The polyketide lipid (810.1) was the best biomarker to differentiate the cancer group from control and polyp. We found no difference between the biomarkers in the polyp group in relation to the control. RESUMO CONTEXTO: O câncer colorretal (CCR) é, mundialmente, uma das principais causas de câncer. Métodos de diagnóstico precoce através de biomarcadores séricos são necessários. O estudo das ômicas, mais recentemente a lipidômica, tem a finalidade de analisar os lipídeos para melhor compreensão do lipidoma humano. A evolução dos métodos de espectrometria de massa, como a tecnologia por MALDI-MS, possibilitou a detecção e a identificação de uma ampla variedade de lipídeos com grande potencial para abrir novos caminhos para a medicina preditiva e preventiva. OBJETIVO: Determinar o perfil lipidômico de pacientes com câncer colorretal e pólipos. MÉTODOS: Foram selecionados pacientes com CCR estádio I-III, com pólipos adenomatosos e indivíduos com colonoscopia normal. Todos os pacientes foram submetidos a coleta do sangue periférico para extração do lipídeo. As amostras foram analisadas por técnica de MALDI-MS para a identificação dos lipídeos. ANÁLISE ESTATÍSTICA: Para análise univariada e multivariada foram utilizados a análise de componentes principais (PCA) e a análise discriminante pelos quadrados mínimos (PLS-DA). Os íons foram identificados de acordo com a classe de lipídeos usando-se o Lipid Maps (http://www.lipidmaps.org). RESULTADOS: Foram incluídos 88 indivíduos, 40 com CCR, 12 com pólipos e 32 controles. A análise de boxbolt evidenciou oito íons VIP nos três grupos. Observou-se diferenças entre os grupos câncer e controle, assim como entre câncer e pólipo, mas não entre pólipos e controle. O policetídeo (810,1) foi o lipídeo hipo-representado no câncer e hiperrepresentado no pólipo e controle. Entre os pacientes com CCR observamos diferenças entre os lipídeos com invasão linfonodal (N1-2) comparados aos sem invasão linfonodal (N0). CONCLUSÃO: Foram identificados possíveis biomarcadores lipídicos entre os pacientes com câncer comparados aos grupos controle e pólipo. O lipídeo policetídeo (810,1) foi o melhor biomarcador para diferenciar o grupo câncer do controle e pólipo. Não encontramos diferença entre os biomarcadores no grupo pólipo em relação ao controle.

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.

Background The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. The objective of the study was to verify the variables involved in the nutritional status and genetic mutations, which correlate with survival of CRC patients. Methods Patients with surgical intervention for tumor resection were evaluated using body mass index, nutritional screening, patient self-produced global subjective assessment, phase angle, and computed tomography to calculate the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue, and muscle mass for the determination of sarcopenia. Ten gene mutations involved in CRC carcinogenesis were studied (PIK3CA, KRAS, BRAF, EGFR, NRAS, TP53, APC, PTEN, SMAD4, and FBXW7). DNA was extracted from fresh tumor or paraffin tissues. Results Of the 46 patients, 29 (64.4%) were at nutritional risk and 21 (45.7%) were moderately malnourished. However, there was a high percentage of VAT in 24 (61.5%) and sarcopenia in 19 (48.7%) patients. These variables were associated with a higher risk of mortality. Nutritional risk, moderate or severe malnutrition, phase angle

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

Background: Colorectal cancer (CRC) is one of the most frequent cancers. Genetic mutations in CRC already described can be detected in feces. Microarray methods in feces can represent a new diagnostic tool for CRC and significant improvement at public health. Aim: to analyze stool DNA by human DNA quantify and microarray methods as alternatives to CRC screening. Method: Three methods were analyzed in stool samples: Human DNA Quantify, RanplexCRC and KRAS/BRAF/PIK3CA (KBP) Arrays. Results: KBP array mutations were presented in 60.7% of CRC patients and RanplexCRC Array mutations in 61.1% of CRC patients. Sensitivity and specificity for human DNA quantification was 66% and 82% respectively. Fecal KBP Array had 35% sensitivity and 96% specificity and RanplexCRC Array method had 78% sensitivity and 100% specificity. Conclusion: Microarray methods showed promise as potential biomarkers for CRC screening; however, these methods had to be optimized to improve accuracy and applicability by clinical routine.

Background - Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. Objective - To quantify the human DNA in the stools of patients with colorectal cancer or polyps. Methods - Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. Results - An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. Conclusion - A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer. Contexto - O câncer colorretal é, mundialmente, uma das principais causas de câncer. A colonoscopia é o melhor método de rastreamento, no entanto a adesão é inferior a 50%. A quantificação de DNA humano (hDNA) nas fezes pode ser um possível método não invasivo de rastreamento, que é consequência da elevada proliferação e esfoliação de células cancerosas. Objetivo - Quantificar o DNA humano nas fezes de pacientes com câncer colorretal ou pólipos Métodos - Cinquenta pacientes com câncer colorretal, 26 pólipos e 53 com colonoscopia normal foram incluídas. DNA total e humano foram analisados a partir de fezes congeladas. Resultados - Maior concentração de hDNA nas fezes foi observada em pacientes com câncer colorretal em comparação com controles e pólipos. Pacientes com tumores localizados no cólon esquerdo apresentaram concentrações mais elevadas de hDNA. Não houve diferença entre pólipos e controles. Um nível de corte de 0.87ng/mL de DNA humano foi determinado para pacientes com câncer colorretal pela curva ROC, com sensibilidade de 66% e especificidade de 86,8%. Para pólipos o nível de corte foi de 0,41, a sensibilidade foi de 41% e a especificidade de 77,4%. Conclusão - Maior concentração de hDNA foi encontrada em pacientes com câncer colorretal. A quantificação de hDNA das fezes pode ser um método de rastreio do câncer colorretal.

Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.

Colorectal cancer is the third most common cancer worldwide, accounting for more than 610,000 mortalities every year. Prognosis of patients is highly dependent on the disease stage at diagnosis. Therefore, it is crucial to investigate molecules involved in colorectal cancer tumorigenesis, with possible use as tumor markers. Heparan sulfate proteoglycans are complex molecules present in the cell membrane and extracellular matrix, which play vital roles in cell adhesion, migration, proliferation, and signaling pathways. In colorectal cancer, the cell surface proteoglycan syndecan-2 is upregulated and increases cell migration. Moreover, expression of syndecan-1 and syndecan-4, generally antitumor molecules, is reduced. Levels of glypicans and perlecan are also altered in colorectal cancer; however, their role in tumor progression is not fully understood. In addition, studies have reported increased heparan sulfate remodeling enzymes, as the endosulfatases. Therefore, heparan sulfate proteoglycans are candidate molecules to clarify colorectal cancer tumorigenesis, as well as important targets to therapy and diagnosis.

Background The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D3 (circulating form) and 1,25(OH)2D3 (active form), in colorectal cancer (CRC) patients. Methods One hundred fifty-two CRC patients and 321 controls were included. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by PCR-RFLP. Those of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing. Results The median serum levels of circulating vitamin D were not different between CRC patients and controls; however, the percentage of those with deficient vitamin D was higher in patients with cancer. The active form of the vitamin D was higher in CRC patients. VDR, CYP27B1 and CYP24A1 polymorphic genotypes had no influence on serum levels of circulating vitamin D. The correlation between circulating and active vitamin D forms was lower among patients with CRC, regardless of the presence or absence of any genetic polymorphism. The mean serum levels of active vitamin D were higher among patients with polymorphic genotype variants of Apa1 or Bsm1. Conclusions CRC patients had a higher frequence of insufficient vitamin D and a higher concentration of active vitamin D. These concentration were higher between patients with polymorphic genotypes variants of ApaI and BsmI, CYP24A1 and CYP27B1. Polymorphic genotypes cause a lower correlation between the forms of vitamin D.

Purpose Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). Patients and methods Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. Results We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44–1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. Conclusion Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. Clinical trials Identification number: EF024-201; Trial registry: NCT01249352 .

Context Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives To investigate the adhesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the first visit and 8-12 weeks after treatment. Results Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically significant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusions Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance. Contexto A capecitabina, uma droga oral, é tão eficaz quanto as drogas quimioterápicas tradicionais. Objetivos Investigar a adesão ao tratamento oral com capecitabina para câncer de mama e colorretal e determinar qualquer correlação com as mudanças na qualidade de vida do paciente. Métodos Pacientes com câncer colorretal ou de mama em uso de capecitabina foram incluídos. A cada consulta os pacientes trouxeram a medicação restante. O questionário de qualidade de vida QLQ- C30 foi aplicado na primeira visita e 8-12 semanas após o tratamento. Resultados Trinta pacientes foram avaliados. A adesão foi de 88,3% para o câncer de cólon metastático, 90,4% para o de cólon não-metastático, 94,3% para o de reto e 96,2% para o de mama metastático. Com exceção da dispnéia, não houve forte correlação entre adesão e as taxas European Organisation for Research and Treatment of Cancer QLQ-C30 em relação a escala funcional ou de sintomas no início ou após quimioterapia. Conclusões O nível de adesão foi bom, embora não houvesse adesão absoluta ao tratamento com capecitabina oral. Os profissionais de saúde, portanto, precisam dar maior atenção a pacientes em regimes de tratamento oral. Os pacientes com menor grau de dispneia tiveram maior adesão. Neoplasias colorretais, terapia

Purpose Chemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of patients with colorectal cancer. The LAR for Chemotherapy-Induced Diarrhea (LARCID) trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population. Patients and Methods Patients with colorectal cancer starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil, capecitabine, and/or irinotecan were randomly assigned to receive octreotide LAR 30 mg intramuscularly every 4 weeks (experimental arm) or the physician's treatment of choice in case of diarrhea (control arm). Results A total of 139 patients were randomly assigned, most of whom received fluorouracil- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n = 68) and 78.9% in the control group (n = 71). Treatment with octreotide LAR did not prevent or reduce the severity of CID. Treatment choices for diarrhea management included loperamide in the majority of patients. No benefit from octreotide LAR was identified in terms of need for diarrhea treatment, opioids, or intravenous hydration or in the rate of hospitalization or quality of life. Conclusion This study could not prove the efficacy of octreotide LAR in the prevention of CID.

Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. Genetic alterations have been associated with an increased risk of cancer and greater tumor aggressiveness. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) genes are important in cell cycle regulation, tumor growth and prostaglandin synthesis. The aim of the present study was to investigate the association between polymorphisms in the COX-2 and 5-LOX genes and the risk of CRC. A case-control study was conducted in patients with CRC matched for gender and age to a control group. DNA was extracted from peripheral leukocytes, and the polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. A specific questionnaire was applied to evaluate smoking, excessive alcohol consumption, physical activity, non-steroidal anti-inflammatory drug use and meat, fiber and fat intake. A total of 185 patients with CRC and 146 controls were studied. The heterozygous GC genotype of the COX-2 gene polymorphism was the most common in the two groups (60.0% in CRC patients and 52.7% in controls). The CC genotype was associated with an increased risk of CRC (odds ratio, 3.63; 95% confidence interval, 1.31–10.1; P=0.013). The homozygous wild-type genotype of the 5-LOX gene polymorphism was detected in 72.4% of the CRC patients and in 71.2% of the control subjects. The homozygous mutant genotype (CC) of the COX-2 gene is an independent risk factor for CRC. No association was found between 5-LOX genotypes and CRC.

Sporadic colorectal cancer (CRC) is a consequence of the accumulation of genetic and epigenetic alterations that result in the transformation of normal colonic epithelial cells to adenocarcinomas. Studies have indicated that a common event in the tumorigenesis of CRC is the association of global hypomethylation with discrete hypermethylation at the promoter regions of specific genes that are involved in cell cycle regulation, DNA repair, apoptosis, angiogenesis, adhesion and invasion. The present study aimed to investigate the epigenetic changes (DNA methylation) in 24 candidate genes in CRC. A total of 10 candidate hypermethylated (HM) and unmethylated (UM) genes were identified that may be useful epigenetic markers for non-invasive CRC screening. The five genes that had the highest average UM percentages in the control group were MLH1 (71.7%), DKK2 (69.6%), CDKN2A (68.4%), APC (67.5%) and hsa-mir-342 (67.4%). RUNX3 (58.9%), PCDH10 (55.5%), SFRP5 (52.1%), IGF2 (50.4%) and Hnf1b (50.0%) were the five genes with the highest average HM percentages in the test group. In summary, the present preliminary study identified the methylation profiles of normal and cancerous colonic epithelial tissues, and provided the groundwork for future large-scale methylation studies.

Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Our goal in this study was to detect c-myc, p21WAF/CIP1, p53, C-erbB-2 and COX-2 immuno-expression in ESCC. Archival formalin-fixed, paraffin-embedded tissues of 18 cases of ESCC (13 biopsies and 5 surgical specimens) were studied, retrospectively, by immunohistochemistry. p53 protein was observed in 50% of the cases, while c-myc was found in 6 of 18 samples (33.33%). All samples (100%) were negative for p21WAF/CIP1. C-erbB-2 oncoprotein and the COX-2 protein were detected in 5.5% (1/18) and 16.66% (3/18) of the cases, respectively. Taken together, our results suggest that c-myc, p53, C-erbB-2 and COX-2 proteins do not correlate with cancer stage or follow-up in ESCC as revealed by immunohistochemistry.

Introduction Vitamin D receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 involved in the production and inactivation of vitamin D can influence vitamin D and the susceptibility to colorectal cancer (CRC). The objective of this study was to investigate the relationship between the risk of CRC and polymorphisms in VDR, CYP27B1 and CYP24A1, lifestyle and dietary habits. Methods The study included 152 patients with CRC and 321 controls. All participants answered a questionnaire on their dietary habits, alcohol consumption and smoking habits. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by performing PCR-RFLP. Identification of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) polymorphisms was performed by gene sequencing. Results Smoking, alcohol use, and low or no consumption of fruit, cereals and dairy products were associated with an increased risk of CRC. A heterozygous genotype Aa or an association genotype aa + Aa of the VDR ApaI polymorphism increased the risk of CRC. The VDR BsmI polymorphism was not significantly associated with the risk of CRC. Multivariate analysis showed that heterozygous and association genotype AT + AA of the rs6013897 polymorphism, genotype CT of the rs158552 polymorphism, association genotype CT + CC and genotypes AA and GG of the rs17217119 polymorphism of CYP24A1, and heterozygous genotype GT and association genotype GT + TT of the rs10877012 polymorphism in CYP27B1 were associated with a higher risk of CRC. Conclusions Dietary habits, lifestyle, and polymorphisms in VDR (ApaI), CYP24A1 (rs6013897, rs158552, rs17217119) and CYP27B1 (rs10877012) were associated with a higher risk of CRC.

Worldwide the percentage of individuals older than 60 years is growing due to the increase in longevity. Age is an important risk factor for cancer and subjects aged over 60 also have a higher risk of comorbidities. Approximately 50 % of neoplasms occur in patients older than 70 years and these patients often have a range of therapies ranging from surgery, adjuvant or neoadjuvant therapy, or even palliative chemotherapy. While the OPAS (Pan American Health Organization) considers elderly subjects to be those aged over 60 years and for the WHO (World Health Organization) it is subjects over 65 years, a major concern for poor prognosis is with cancer patients over 70–75 years. These patients have a lower functional reserve, a higher risk of toxicity after chemotherapy, and an increased risk of infection and renal complications that lead to a poor quality of life. Several biomarkers (immunological and physiological) have been evaluated in cancer aiming to improve diagnostics, to predict whether a patient could have any benefit from a specific treatment, and to perform patient follow-up. Cancer is a complex disease and in this chapter we will discuss the distribution of cancer cases in older adults, the most important types of cancer in this population, treatment and outcomes, and possible immunosenescence characteristics related to cancer in the aged.

Background - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. Objective - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. Methods - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value

OBJECTIVE: Gastric cancer (GC) is one of the most common cancers, and its incidence increases with age. The objective of the study was to evaluate the response rate (RR), overall survival (OS), and toxicity in patients aged over 60 years, with metastatic GC and who were undergoing chemotherapy. METHODS: This is a retrospective study developed in a university hospital. Medical records of patients treated in the last 4 years were analyzed. RESULTS: Twenty-one patients were included; the average age was 69.6 ± 7.6 years, 76.2% men, 61.9% Karnofsky Performance Status (KPS) > 70, 85.7% had weight loss > 10% in 6 months, 28.6% had at least 2 sites of metastasis, and 42.9% had unfavorable histology (diffuse). Most of the patients (85.7%) were treated with combination regimens (4.6 cycles on average). Patients with better nutritional status had a non-statistically significant better tolerance to the treatment (p = 0.17). The median progression-free survival (PFS) was 9.0 months and the median OS was 13.8 months. Toxicity grade 1-2 was observed in 61.9%, and grade 3-4, in 14.3%. Less than two sites of metastasis (hazard ratio [HR] = 0.15; CI95% 0.02 - 0.93), absence of metastasis to non-regional lymph nodes (HR = 0.04; CI95% < 0.01 - 0.44), higher number of chemotherapy cycles (HR = 0.72; CI95% 0.53 - 0.97), objective response (HR = 0.06; CI95% 0.01 - 0.69) were associated with higher OS. Higher body mass index (BMI) was related with a not statistically significant better OS (HR = 0.84; CI95% 0.64 - 1.10). CONCLUSIONS: Patients treated in our hospital showed results compatible with literature. The doublet chemotherapy is feasible in elderly individuals with manageable toxicity.

Adjuvant or neoadjuvant chemoradiotherapy (CRT) increases the survival rates significantly, but it also increases morbidity. Molecular markers may help on prognosis evaluation and treatment choice. The purpose of this study is to evaluate the imunoexpression of p53 and Ki-67 in rectal cancer tissue after CRT treatment. Stage II or III rectal cancer patients were evaluated and treated with RT and 5-FU preoperatively (neoadjuvant treatment, NG) or after surgical resection of the cancer (adjuvant treatment, AG). Thirty-one patients were enrolled in the NG and 30 in the AG; 63.95% were between 50 and 70 years, 50.8% were male, and 53% were in stage III. Of the tumors, 64.5% of the NG and 63.34% of the AG had not overexpressed p53 (p = 0.865) and 9.67% of NG and 33.33% of the AG tumors had a high proliferative index (HPI) of Ki67, p = 0.052. We have not found any difference among metastasis development in the groups (p = 0.708). After 5 years, patients with low proliferative index (LPI) of Ki67 tumors had the best survival rate (p = 0.041). Patients with positive or negative p53 tumors had similar survival (p = 0.35). Patients with HPI of Ki67 had an increased marginal risk for death (p = 0.069). The rate of tumors that overexpressed p53 was similar in both groups. Patients with p53 positive tumors survived as long as those with p53 negative. Patients treated with chemoradiotherapy before surgical resection, expressed Ki67 in a small percentage. Rectal cancer patients with LPI of Ki67 had the best prognosis.

e13623Background: Lynch syndrome (LS) is the most common inherited colorectal cancer syndrome (CRC), comprising 2-4% of CRC, that may cause others cancers. Individuals with LS have at least one MMR...

Cancer has been seen negatively by the people that disclose fear and anxiety face to the disease closely associated with distress, aggressive treatments, and death. Colorectal cancer is one of the most prevalent cancer and few assays were developed studying depression and anxiety in patients after surgical resection of tumor and before adjuvant therapy.This research aims to study the prevalence of depression and anxiety in patients with colorectal cancer before and after adjuvant chemotherapy.After surgical resection of colorectal cancer, 37 patients were included according to the kind of treatment: chemotherapy group (CHG) and the other one without indication of chemotherapy, the control group (CG). Questionnaires of Depression and Anxiety were done at the beginning and at the end of the treatment in the CHG (n = 19) and at the first and after 6 months of follow-up (n = 18) in the CG.No difference on gender, age, or site was observed among the groups. Stage III tumor was more frequent in the CHG group. Mild or moderate depression was diagnosed in 31.6% of the CHG patients in the first evaluation and in 38.6% at the second one. In the CG no depression was observed in both evaluations. About the State-Trait Anxiety Inventory, the results were similar before and after chemotherapy treatment. There was a higher number of patients with moderate state or trait anxiety in the CHG when compared to the CG in both evaluations. No correlation was found about the inventories of anxiety and depression and site of tumor or stage.After surgical treatment of colorectal cancer, depression and indexes of anxiety were higher in the group of patients treated with chemotherapy when compared to the control group.

Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle. A common G to A polymorphism in the CCND1 gene is implicated on the splicing of the CCND1 transcript, and this protein may be associated to a deregulated cell proliferation. Correlate the polymorphism A870G of CCND1 to the risk of colorectal cancer (CRC), to environmental risk factors and clinical aspects in Brazilian patients. One hundred twenty-three Brazilian patients with colorectal cancer were matched by age and sex to 120 healthy individuals. PCR-RFLP was performed to investigate the A870G CCND1 genotype. Between the cases 70 were men, the mean age was 62.6 years, 74.78% were stage II or III, and 91% were well or moderately differentiated. The patients were followed for a mean time of 37.22 months. The frequency of ethanol and fat intake was similar among the groups. Patients with a family history of CRC had a higher frequency of CRC compared with the controls (OR 4.16, CI 1.89–9.16). There was no difference in the frequency of the alleles A (43.8% versus 43.9%) and G (56.3% versus 56.1%) in the groups. In analysis of both control and cancer group, the influence of sex, smoking, alcohol, fiber, or meat intake did not differ significantly according to CCND1 genotype. The genotype AA or AG was associated with an increased risk of CRC (OR 3.63 CI 1.25–10.5) in patients with a family history of cancer. We did not find any association among the genotypes and localization of the tumor or prognosis. Although a difference on age onset of the tumor and genotype was not observed, patients with GG genotype had a mean 8 years lower than the others. This genotype was also associated to an increase risk of metastatic disease (OR 3.47, CI 1.38–8.68, p = 0.024). We did not find a correlation among the polymorphism of CCND1 A870G and colorectal cancer risk or between this polymorphism and lifestyle habits, diet, or follow-up. GG genotype patients had an increased risk of advanced disease and between the young patients, this genotype was associated to a lower mean age. On the other hand, the genotype AA or AG had been involved to a higher risk of CRC in patients with family history of CRC.

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1%). Histological examination revealed fundic type epithelium in 58.3% of cases, H. pylori was present in 50% and chronic inflammation in 66.7%. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7% of cases and Barrett's esophagus in 90% of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Background Despite the decreased incidence, gastric cancer is still a frequent cause of cancer related death. The 1st line 2 or 3 drugs regimen is still a debatable issue. HER2 targeted therapy has emerged as the standard of care, but it is unavailable in the Brazilian Public Health System. The end-point of this trial was overall survival (OS) in patients with metastatic gastric cancer treated in a public university hospital in Brazil. The secondary end-points were efficacy and safety of regimens with 2 (F+P) or 3 (EOX) drugs to develop an institutional guideline to facilitate optimal treatments. Materials and methods In this retrospective study, 1st line regimens were evaluated for OS and PFS stratified by age and ECOG using Cox regression. Results 47 patients were treated over the last 3 years. In 1st line, 29 were treated with F+P (mean 59.3 years, 34.5% ECOG 2 and a mean of 5.69 cycles) and 16 with EOX (mean 47 years, 18.8% ECOG 2 and a mean of 5.44 cycles). The median OS was 13.8 months (95%CI 10.7-16.9). Response was evaluated in 40 cases and was 64.3% for EOX and 37.5% for F+P (p=0.25). The median PFS was 9.5 months for EOX and 5.6 months for F+P (HR 0.85, 95%CI 0.41-1.74). However, among patients with ECOG 2 mPFS was 3.70 vs 5.40 months, respectively (p=0.86). Regimens showed similar manageable adverse events. A total of 34 patients suffered progression and 14 received 2nd line therapy. Diffuse histology (HR 1.89, 95%CI 1.22-2.88), achieving 2nd line (HR: 0.25, 95%CI 0.11-0.58) and treatment response (HR 0.23, 95%CI 0.12-0.47) were OS prognostic factors. Conclusions Patients treated in our hospital had outcomes compatible with the literature. The regimen choice should be related to patient features. Second line treatment should be considered.

RACIONAL: O câncer colorretal é a quarta causa de câncer no Brasil e o 5-fluourouracil uma das principais drogas usadas no tratamento adjuvante e paliativo dessa doença. A toxicidade da quimioterapia e as alterações de qualidade de vida, causadas pela própria doença e pelo tratamento, são motivo de muitos estudos. OBJETIVO: Avaliar nos doentes com câncer colorretal em tratamento quimioterápico, a toxicidade e possíveis alterações da qualidade de vida. MÉTODOS: Durante o período de março de 2001 a maio de 2003 no Ambulatório de Oncologia da Disciplina de Gastroenterologia Clínica da Universidade Federal de São Paulo, foram acompanhados 45 pacientes com câncer colorretal em tratamento quimioterápico adjuvante ou paliativo com 5-fluourouracil e ácido folínico durante seis ciclos. A toxicidade gastrointestinal e hematológica foi analisada utilizando-se as Recomendações para a Graduação da Toxicidade Aguda e Subaguda. Após o término de cada ciclo quimioterápico, os resultados foram anotados de acordo com os respectivos graus que variaram entre 0 e 4. A qualidade de vida foi pesquisada pelo questionário WHOQOL bref (World Health Organization Quality of Life) que consta de 26 questões e é composto por 4 domínios: físico, psicológico, relações sociais e meio ambiente, no início, no 3° e no 6° ciclo de tratamento. RESULTADOS: Entre os 45 pacientes, 28 eram do sexo masculino, a média de idade foi de 58,4 anos (34 a 79 anos). Segundo a classificação da União Internacional Contra o Câncer, 34 (75,6%) eram estádio II ou III e 11 estádio IV (24,4%). Quanto à localização, 64,4% eram de cólon. Em 57,7% a quimioterapia foi adjuvante e nos demais paliativa. As toxicidades mais comumente encontradas foram náuseas (42%), diarréia (38%) e neutropenia (15,7%). Não houve diferença significante entre os graus de toxicidade nos diferentes ciclos, assim como entre os doentes em tratamento adjuvante ou paliativo. Quanto à qualidade de vida foram observadas alterações significantes nos domínios físico e psicológico quando comparadas a primeira com a segunda ou a primeira com a terceira aplicação do questionário. Não foi encontrada alteração da qualidade de vida entre os doentes em quimioterapia adjuvante quando comparada aos em tratamento paliativo. Independente da indicação terapêutica, a média dos escores de qualidade de vida diminuiu em relação aos domínios físico e social na terceira aplicação do teste. CONCLUSÃO: As toxicidades gastrointestinais foram mais freqüentes que as hematológicas com o esquema utilizado. A qualidade de vida diminuiu após o início da quimioterapia em relação à atividade física e psicológica. No estudo da média dos escores observou-se queda dos mesmos nos domínios físico e social. A análise do questionário não mostrou alteração de qualidade vida quando comparados os doentes em tratamento paliativo com os em adjuvância. BACKGROUND: The colorectal cancer is the fourth cause of cancer in Brazil and 5-fluorouracil is the drug most commonly used in the adjuvant or palliative treatment of this disease. AIM - Evaluating in patients with colorectal cancer and chemotherapy, the toxicity and the quality of life. PATIENTS AND METHODS: From March 2001 and May 2003, 45 patients treated with colorectal cancer treated with 5-fluourouracil and folinic acid were followed closely during six cycles. The gastrointestinal and hematologic toxicity was analysed making use of the chart "Recommendations for the Graduation of Acute and Subacute Toxicity". After the end of each cycle of chemotherapy, the results were registered according to the respectives degrees that vary from 0 to 4. The quality of life was researched through the WHOQOL bref (World Health Organization Quality of Life) questionary that consists of 26 questions and 4 domains: physical, psychological, social relations and environmental, in the beginning, on the 3rd and 6th cycles of treatment. RESULTS: Among the 45 patients, 28 were male, the average age was 58.4 years old (from 34 to 79 years old). According to the International Union Against Cancer classification, 34 patients (75.6%) had tumors stage II or III and 11 had tumors stage IV (24.4%), 64.4% were in the colon. In 57.7% the chemotherapy was adjuvant and in the others palliative. The toxicities more commonly found were nauseas (42%), diarrhea (38%), and neutropenia (15.7%). There was no significant difference among the degrees of toxicity in the different cycles as well as among the patients in adjuvant or palliative treatment. Significant alterations was found among the quality of life in the physical and psychological domains when the 1st and the 2nd or the 1st and the 3rd application of the test were done. Alterations of the quality of life were also found in the social domain when the first evaluation was compared with the last one. There was no difference between the quality of life and the treatment.

RACIONAL: Polimorfismos genéticos são variações genéticas que podem ocorrer em seqüências codificadoras e não-codificadoras, levando a alterações qualitativas e/ou quantitativas das proteínas em questão. O p53 é o gene mais comumente alterado no câncer humano. O polimorfismo desse gene no códon 72 ocorre por substituição de uma base e tem sido associado a maior risco de câncer. OBJETIVO: Determinar a possível associação entre o polimorfismo no códon 72 (72 arginina/prolina) do gene p53 e câncer colorretal. CASUÍSTICA E MÉTODOS: Foram avaliados em 100 pacientes com câncer colorretal e em 100 indivíduos sem câncer, pareados quanto ao sexo idade, o hábito de fumar, o etilismo e no grupo caso o estádio, o grau de diferenciação e a evolução da doença. O genótipo (72 arginina/prolina) foi determinado por PCR, utilizando-se primers (seqüências de nucleotídeos) específicos. RESULTADOS: O genótipo homozigoto arginina/arginina foi prevalente em 56% no grupo controle e em 58% no grupo caso. Não se observou diferença entre os dois grupos. No estádio IV este genótipo foi mais freqüente quando comparado ao estádio I (80% versus 14%). Não se observou diferença entre as variações do genótipo e fumo, álcool, evolução clínica ou grau de diferenciação. CONCLUSÃO: A prevalência do genótipo arginina/arginina foi a mais freqüente nos dois grupos. Não foi encontrada correlação entre maior risco de câncer e o polimorfismo no códon 72 prolina/arginina do gene p53. Apesar do pequeno número de doentes com câncer em estádio avançado (IV), estes tiveram maior prevalência do genótipo arginina/arginina. BACKGROUND: Polymorphisms are genetic variations that can occur in sequences of codons, leading to defective proteins. p53 is the most commonly gene affected in human cancer. The polymorphism of this gene occurs by a substitution of a base in codon 72 and may increase the risk of cancer. AIM: To investigate the possible association between p53 arginine/72 proline polymorphism and susceptibility to colorectal cancer. PATIENTS AND METHODS: This polymorphism was studied by polymerization chain reaction using specific primers in 100 patients with colorectal cancer paired by sex and age to 100 patients without cancer. Alcohol and tobacco used by all the patients and clinical aspects as stage, grade of differentiation and recurrence in the case group was compared with the genotype analyzed. RESULTS: The frequency of homozygosis for arginine was 56% in the cancer group and 58% in the control group. No significant difference was observed among both groups. This genotype was more frequent in colorectal cancer patients stage IV than in stage I (80% versus 14%). There was no significant difference between genotypes and alcohol, tobacco, grade of differentiation or recurrence. CONCLUSION: Homozygosity for arginine was the most prevalent genotype in both groups. The frequency of codon 72 proline/arginine p53 gene polymorphism was not correlated with a higher risk of colorectal cancer. Arginine/arginine genotype was more prevalent in advanced cancer patients (stage IV).

Primary small intestine cancers are not frequent, accounting for

Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. The AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.

Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.

Gastric cancer (GC) remains a virtually incurable disease when metastatic and requires early screening tools for detection of early tumor stages. Therefore, finding effective strategies for prevention or recurrence of GC has become a major overall initiative. RNA-interference (RNAi) is an innovative technique that can significantly regulate the expression of oncogenes involved in gastric carcinogenesis, thus constituting a promising epigenetic approach to GC therapy. This review presents recent advances concerning the promising biomolecular mechanism of RNAi for GC treatment.

Introdução - Estudos epidemiológicos e gênicos mostram que os pólipos colônicos do tipo adenoma são lesões pré-neoplásicas. O seguimento de um paciente com câncer colorretal visa principalmente o diagnóstico e retirada de pólipos adenomatosos. Objetivo - Estudar a freqüência do aparecimento de pólipos adenomatosos em doentes com câncer colorretal em acompanhamento clínico após ressecção tumoral. Casuística e Métodos - Foi estudada, retrospectivamente, a freqüência de pólipos do tipo adenoma em 68 pacientes com idade média de 59 anos, submetidos a cirurgia curativa para tratamento de câncer colorretal e a colonoscopia de controle. Resultados - A incidência de pólipos adenomatosos foi de 18%, sendo maior acima de 45 anos (20%) e no cólon esquerdo (38%). Em relação ao tipo histológico, 61% eram tubulares, 22% vilosos e 17% túbulo-vilosos. Discussão - Assim como em outros relatos da literatura, a incidência de pólipos foi superior em indivíduos com mais de 45 anos, sendo em mais da metade do tipo tubular. A freqüência de pólipos foi maior nos dois primeiros anos de acompanhamento.