Estudo de biomarcadores lipídicos em pacientes portadores com pólipos e câncer colorretal / Study of lipid biomarkers of patients with polyps and colorectal câncer

ABSTRACT 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.

Adiponectina, vitamina D e estado nutricional em pacientes com câncer colorretal avançado e em seguimento / Adiponectin, vitamin d and nutritional status in patients with advanced colorectal cancer or during follow-up

ABSTRACT 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.

RESUMO CONTEXTO: Considerando a alta incidência de óbitos devido ao câncer coloretal (CCR), estudos investigaram variáveis que podem afetar a sobrevida, com objetivo de prolongar a sobrevida. O estado nutricional desses pacientes também pode predizer a sobrevida. OBJETIVO: O objetivo do presente estudo foi avaliar se o índice de massa corporal (IMC), a porcentagem de gordura, os níveis séricos de adiponectina e de vitamina D são relevantes para a caracterização e diferenciação de pacientes com CCR avançado e pacientes com histórico de CCR. MÉTODOS: O estudo foi realizado por pacientes com câncer colorretal avançado (Grupo 1) e pacientes em acompanhamento após o tratamento do CCR (Grupo 2). O estado nutricional foi avaliado por meio do IMC, percentual de gordura corporal, ângulo de fase da bioimpedância elétrica, escore de Avaliação Global Subjetiva Gerada pelo Paciente. As concentrações de adiponectina foram determinadas por ELISA e os níveis de vitamina D foram medidos por meio de cromatografia líquida de alta performance. RESULTADOS: Os grupos 1 e 2 consistiram de 23 e 27 pacientes, respectivamente. O IMC, percentual de gordura corporal, ângulo de fase, níveis de vitamina D e adiponectina não foram significativamente diferentes entre os grupos. O escore médio da Avaliação Global Subjetiva Gerada pelo Paciente foi significativamente maior no grupo 1 em comparação com o Grupo 2, e foi significativamente correlacionado com o risco de mortalidade a longo prazo. CONCLUSÃO: Entre os indicadores do estado nutricional, apenas o escore da Avaliação Global Subjetiva Gerada pelo Paciente foi significativamente diferente entre os grupos e foi um importante preditor de sobrevida em pacientes com câncer colorretal avançado.

Effect of FOLFOX6 chemotherapy on serum VEGF expression in advanced colorectal cancer patients

SUMMARY OBJECTIVE: To explore the effect of FOLFOX6 chemotherapy on serum vascular endothelial growth factor (VEGF) expression in advanced colorectal cancer patients. METHODS: A retrospective analysis of 81 patients with advanced colorectal cancer who visited our hospital from March 2014 to February 2016 was performed. All the patients were treated with FOLFOX6 chemotherapy. On day 1, patients received oxaliplatin 100 mg/m2 ivgtt (2h), calcium folinate 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus and 5 fluorouracil 2500 mg/m2 ivgtt (5h). The treatment course was 2 weeks, and 4 treatment courses were required. The changes in the levels of VEGF and CRP and quality of life before and after 4 courses of chemotherapy were observed and therapeutic effects and adverse reactions after chemotherapy were evaluated. RESULTS: After treatment, the total efficiency of chemotherapy was 82.72% (67/81) with 24 cases in complete remission, 25 cases in partial response, 18 cases in stable disease and 14 cases in progressive disease. The levels of CRP and VEGF after the treatment were significantly lower than those before treatment (5.69±0.77) mg/L vs. (7.99±1.36) mg/L; (443.26±21.55) pg/mL vs. (542.83±20.44) pg/mL] (P<0.05). The KPS grade after treatment was significantly higher than that before treatment (57.84±4.6) point vs. (50.99±3.73) point] (P<0.05). Among them, 3 cases developed a rash, 5 cases experienced hair loss, and 9 cases developed nausea and vomiting. CONCLUSION: FOLFOX6 chemotherapy can decrease serum VEGF expression in patients with advanced colorectal cancer and enhance the curative effect with high safety, which is good for the improvement of patients' survival.

RESUMO OBJETIVO: Explorar o efeito da quimioterapia Folfox6 na expressão do fator de crescimento endotelial vascular sérico (VEGF) em pacientes com câncer colorretal avançado. MÉTODOS: Uma análise retrospectiva de 81 pacientes com câncer colorretal avançado que visitaram nosso hospital de março de 2014 a fevereiro de 2016 foi realizada. Todos os pacientes foram tratados com quimioterapia Folfox6. No dia 1, os doentes receberam oxaliplatina 100 mg / m2 ivgtt (2h), folinato de cálcio 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus e 5 fluorouracil 2.500 mg/m2 ivgtt (5h). O curso de tratamento foi de duas semanas e foram necessários quatro cursos de tratamento. Foram observadas as alterações nos níveis de VEGF e CRP e qualidade de vida antes e após quatro cursos de quimioterapia e avaliados os efeitos terapêuticos e reações adversas após a quimioterapia. RESULTADOS: Após o tratamento, a eficácia total da quimioterapia foi de 82,72% (67/81), com 24 casos em remissão completa, 25 casos em resposta parcial, 18 casos em doença estável e 14 casos em doença progressiva. Os níveis de CRP e VEGF após o tratamento foram significativamente inferiores aos do tratamento (5,69 ± 0,77) mg / L vs. (7,99 ± 1,36) mg / L; (443,26 ± 21,55) pg / mL vs. (542,83 ± 20,44) pg / mL] (P < 0,05). O grau de KPS após o tratamento foi significativamente maior do que antes do tratamento (57,84 ± 4,6 pontos) vs. (50,99 ± 3,73 pontos)] (P < 0,05). Entre eles, três casos desenvolveram erupção cutânea, cinco casos sofreram perda de cabelo e nove casos desenvolveram náuseas e vômitos. CONCLUSÃO: A quimioterapia Folfox6 pode, obviamente, diminuir a expressão de VEGF no soro em pacientes com câncer colorretal avançado e melhorar o efeito curativo com alta segurança, o que é bom para a melhoria da sobrevivência dos pacientes.

Identificação de células tumorais circulantes e outros componentes sanguíneos em pacientes com câncer de cólon localizado / Identification of circulating tumor cells and other blood componentes in localized colon cancer

Introdução: A detecção precoce do câncer de cólon proporciona altas taxas de cura, no entanto, há pacientes que apresentam recidiva local e metástase à distância. As células tumorais circulantes (CTCs) e os microêmbolos circulantes (MEs) desempenham um papel importante nestes processos. Objetivo: avaliar o papel de CTCs e MEs em pacientes com câncer de cólon localizado. Material e métodos: foram coletados 10 mL de sangue de pacientes com câncer de cólon pré-cirúrgico, pré-adjuvância e 6 meses após o final do tratamento. As amostras foram processadas no dispositivo ISET® e as CTCs foram fixadas com formaldeído e identificadas por imunocitoquímica. Para detecção de expressão de RNAm, foi realizada a técnica de hibridização in situ cromogênica. O DNA foi extraído das membranas sem formaldeído e analisado por PCR digital em gotas. Resultados: no módulo I, foram incluídos 69 pacientes (18 com estágio I, 15 com estágio II e 36 com estágio III). A taxa de detecção de CTCs na primeira coleta foi de 94,2%, de 94,6% no primeiro seguimento e de 100% no segundo seguimento. Foi observada uma queda global na mediana de CTCs ao longo do tempo. No segundo seguimento, a expressão de ERCC1 e de ß-galactosidase nas CTCs foi mais encontrada em pacientes com estágio III (p= 0,03 e p= 0,04, respectivamente). A expressão de ERCC1 com alto índice de positividade (IP) nas CTCs, no segundo seguimento foi determinante de sobrevida livre de recidiva (SLR) inferior (p= 0,014). Foi encontrada uma correlação positiva entre o nível de CTCs e a porcentagem de células TReg (p= 0,01) e negativa entre o nível de CTCs e a porcentagem de linfócitos CD3+ (p= 0,01). Pacientes com alta Platelet-to-Lymphocyte Ratio (PLR) encontravam-se em sua maioria com estadiamentos patológicos II de alto risco e III (p= 0,014). Alta PLR foi determinante de SLR inferior (p= 0,01). No módulo II (pacientes com tumores de alto risco, submetidos à quimioterapia adjuvante) foi encontrada uma correlação positiva entre os níveis de CTC e CEA nos casos que tiveram recidiva da doença (p= 0,001). Alto IP de ERCC1 no segundo seguimento foi determinante de SLR significantemente inferior (p= 0,013). Conclusões: CTCs foram encontradas em altas taxas nos pacientes com câncer de cólon localmente avançado. A avaliação do sistema imunológico dos pacientes juntamente com as CTCs demonstrou ser uma ferramenta promissora para acompanhamento destes pacientes

Introduction: The early detection of colon cancer provides high cure rates, however, there are patients that present local relapse and distant metastasis. Circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) play a crucial role in these processes. Objectives: to evaluate the role of CTCs and CTM in non-metastatic colon cancer patients. Material and methods: 10 mL of blood were collected from colon cancer patients prior to the surgery, prior to the adjuvant treatment, and 6 months after the treatment end. Samples were processed in the ISET® device and CTCs were formaldehyde-fixed and identified by immunocytochemistry. For mRNA expression in situ hybridization was applied. The DNA was extracted from the non-fixed CTCs and analyzed by droplet digital PCR. Results: there were 69 patients included (18 at stage I, 15 at stage II, and 36 at stage III) at module I. The CTC detection rate at baseline was 94.2%, at first follow-up was 94.6%, and at second follow-up was 100%. It was observed an overall drop in CTC median over time. At second follow-up, ERCC1 and ß-galactosidase expression in CTCs was most commonly found in stage III patients (p= 0.03 and p= 0.04, respectively). High positivity index (PI) of ERCC1 in CTC at second follow-up was determinant of inferior relapse-free survival (RFS) (p= 0.014). It was found a positive correlation between CTC levels and the percentage of TReg cells (p= 0.01) and a negative correlation between CTC levels and the percentage of CD3+ lymphocytes. Patients with high Platelet-to-Lymphocyte Ratio (PLR) were mostly found in high-risk stage II and III patients (p= 0.014). High PLR was determinant of inferior RFS (p= 0.01). At module II (patients with high-risk tumors, treated with adjuvant chemotherapy), it was found a positive correlation between CTC and CEA levels in the cases that shown disease progression (DP) (p= 0.001). High PI of ERCC1 at second follow-up had shown significantly worse RFS (p= 0.013). Conclusions: CTCs were found in high rates in localized colon cancer patients. Additionally, the evaluation of the patient's immune combined with the CTCs showed to be a promising tool to monitoring these patients

Serological under expression of microRNA-21, microRNA-34a and microRNA-126 in colorectal cancer

PURPOSE: This paper describes the ability of miRNA value predict oncological outcomes in CRC patients and correlates to clinical and pathologic variables. METHODS: We prospectively analyzed the serological expression of microRNA-21, microRNA-34a, and microRNA-126 in 37 stage II - IV CRC patients and correlate to seven fit counterparts. Serological microRNAs were extracted using the miRNeasy Mini Kit(r) (Qiagen, Hilden, Germany). Quantification of microRNAs was performed using TaqMan Master Mix(r) reagent (Applied Biosystems, USA). RESULTS: We obtained serological underexpression microRNA-21, microRNA-34a, and microRNA-126 in CRC group. However, miRNAs serological values do not impact prognosis. Furthermore, miRNAs was not influenced by CEA values, TNM staging, and histological subtype. CONCLUSION: Despite lower expression of miR-21, miR-34a and miR-126 in the CRC group, no association with poor prognosis was found.

Copper-Zinc ratio and nutritional status in colorectal cancer patients during the perioperative period

PURPOSE : This study aimed to determine Cu/Zn ratio, nutritional and inflammatory status in patients during the perioperative period for colorectal cancer. METHODS: The study included patients with histological diagnosis of colorectal adenocarcinoma (Cancer Group, n=46) and healthy volunteers (Control Group, n=28). We determined habitual food intake, body composition, laboratory data of nutritional status, serum calprotectin and plasma Cu and Zn concentrations. Mann-Whitney U-test was performed between-group comparisons and Spearman correlation test for correlations between the variables. RESULTS: Individuals in the Cancer Group presented significantly lower BMI, fat mass, plasma hemoglobin, total protein and albumin as compared with the Control Group. Serum calprotectin[70.1 ng/mL (CI95% 55.8-84.5) vs.53.3 ng/mL (40.3-66.4), p=0.05], plasma Cu concentrations [120 µg/dL(CI95% 114-126) vs. 106 µg/dL(CI95% 98-114), p<0.01] and the Cu/Zn ratio [1.59 (CI95% 1.48-1.71)vs. 1.35 (CI95% 1.23-1.46), p=0.01]were higher in patients with colorectal cancer than in controls. Additionally, the Cancer Group showed negative correlations between the Cu/Zn ratio and Zn intake, hemoglobin, serum albumin, and positive correlation between the Cu/Zn ratio and serum calprotectin. CONCLUSION: These results indicate that an increased plasma Cu/Zn ratio and serum calprotectin, and decreased protein values may be a result of the systemic inflammatory response to the tumor process.

Prognostic Inflammation Score in Surgical Patients with Colorectal Cancer

Several inflammatory markers have been investigated as prognostic parameters in a variety of cancer population with mostly favorable results. This study aimed to verify the significance of common inflammatory markers as prognostic variables and assess whether a selective combination of them as prognostic inflammation score (PIS) could further improve their prognostic values in surgical patients with colorectal cancer (CRC). A total of 265 patients who had undergone curative resection of CRC were reviewed retrospectively. Preoperative levels of inflammatory markers such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and neutrophil/lymphocyte ratio (NLR) were assessed by uni- and multivariate survival analysis with disease-free (DFS) and disease-specific survival (DSS). PIS was constructed with a selective combination of inflammatory markers which were independently significant. On univariate analysis, CRP, ESR, and NLR were significantly associated with DFS and DSS. On multivariate analysis, CRP and NLR were independently significant prognostic variables for DSS and DFS respectively (P=0.013, P=0.021). When PIS was constructed with combination of CRP and NLR, it was independently and significantly associated with both DFS and DSS (P=0.006, P=0.010). Furthermore, PIS was superior to CRP for DSS (HR=15.679 vs. HR=5.183), and NLR for DFS in terms of prognosticating power (HR=4.894 vs. HR=2.687). When PIS is constructed with combination of CRP and NLR, it is a potentially significant prognostic variable associated with poor survival regardless pathologic prognostic variables in patients with CRC after curative resection.

Indicadores del proceso de tamizaje de cáncer de mama en México: un estudio de caso / Breast cancer screening process indicators in Mexico: a study case

Objetivo. Identificar, medir y comparar indicadores de desempeño de productividad, acceso efectivo y calidad en el servicio del programa de detección oportuna de cáncer de mama en México. Material y métodos. Mediante un estudio de caso basado en datos del Sistema de Información de Cáncer de la Mujer (Sicam) 2011, se midieron y compararon los indicadores con la Norma Oficial Mexicana NOM-041-SSA2-2011 y con estándares internacionales. Resultados. El análisis mostró capacidad instalada insuficiente (37%), bajas coberturas en tamizaje (15%), evaluación diagnóstica (16%), biopsia (44%) y tratamiento (57%) y muy baja efectividad en la detección de casos confirmados por número de mastografías realizadas (0.04%). En el Sicam no existe información para estimar el resto de indicadores propuestos. Conclusiones. Se requieren sistemas de información en salud eficientes para monitorear indicadores y generar observatorios del desempeño de los programas de detección.

Objective. To identify, measure and compare the performance indicators of productivity, effective access and quality service for the early detection breast cancer program in Mexico. Material and methods. By means of a study case based on the 2011 Women Cancer Information System (Sicam), the indicators were measured and compared with the Mexican official standard NOM-041-SSA2-2011 and international standards. Results. The analysis showed insufficient installed capacity (37%), low coverage in screening (15%), diagnostic evaluation (16%), biopsy (44%) and treatment (57%), and very low effectiveness in confirmed cases by the total number of screening mammograms performed (0.04%). There was no information available, from Sicam, to estimate the rest of the indicators proposed. Conclusions. Efficient health information systems are required in order to monitor indicators and generate performance observatories of screening programs.

Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

Ischemia-Modified Albumin: Could It Be a New Oxidative Stress Biomarker for Colorectal Carcinoma?

BACKGROUND/AIMS: An impaired oxidative/antioxidative status plays an important role in the pathogenesis of many diseases, including cancer. The aim of this study was to evaluate the levels of the novel marker ischemia-modified albumin (IMA) and albumin-adjusted IMA (Adj-IMA) in patients with colorectal cancer (CRC) and look for the associations of these with the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). METHODS: Forty patients with CRC (19 females and 21 males; mean age, 56.5+/-2.1 years) and 39 age- and sex-matched healthy people (22 females and 17 males; mean age, 56.0+/-1.7 years) were included in this study. Serum levels of IMA, TAS, and TOS were analyzed, and the OSI was calculated. RESULTS: Serum IMA, TOS, and OSI levels were significantly higher in patients with CRC than in controls (p<0.0001), whereas TAS levels were significantly lower in CRC patients (p=0.03). There was no significant difference in serum Adj-IMA levels between groups (p=0.32). CONCLUSIONS: In this study, the oxidative/antioxidant status was impaired in favor of oxidative stress in CRC patients. This observation was not confirmed by IMA measurement. Further studies are needed to establish the relationship between IMA and oxidative stress parameters in CRC and other cancers.

Níveis séricos pré-operatórios dos marcadores CEA e CA19-9 e imunoexpressão tecidual do marcador CA19-9 no carcinoma colorretal: relação com os aspectos morfológicos da neoplasia / Pre-operative sera levels of CEA and CA19-9 and tissular distribution of tumor marker CA19-9 in colorectal carcinoma: correlation with morphological features of neoplasia

OBJETIVO: Comparar os níveis séricos de CA19-9 e CEA e a expressão tecidual do CA19-9 e relacioná-los com os aspectos morfológicos do carcinoma colorretal. MÉTODOS: Quarenta e cinco pacientes com carcinoma colorretal foram operados com coleta de CEA e CA19-9 séricos pré-operatórios. Valores séricos de CEA = 5,0ng/mL e de CA19-9 = 37UI/mL foram considerados aumentados. A avaliação da imunoexpressão do CA19-9 no tecido neoplásico foi realizada por meio de estudo imunoistoquímico com anticorpo monoclonal anti-CA19-9. A intensidade de expressão do CA19-9 no tecido neoplásico foi semiquantificada em leve(+/+++), moderada(++/+++), intensa(+++/+++) e ausente. RESULTADOS: Os valores do CA19-9 sérico foram progressivamente maiores conforme o aumento da expressão do CA19-9 no tecido neoplásico, porém sem significância (p=0,06). O aumento do nível sérico do CA19-9 foi acompanhado de elevação significante (p<0,001) do nível sérico do CEA. O nível sérico do CA19-9, a imunoexpressão tecidual do CA19-9 e o nível sérico do CEA não apresentaram associação significante com características morfológicas do carcinoma colorretal. CONCLUSÃO: As expressões sérica e tissular do CA19-9 demonstraram relação diretamente proporcional entre si, enquanto que os aspectos morfológicos da neoplasia não tiveram influência no CEA e CA19-9 séricos ou na imunoexpressão do CA19-9 tissular.

OBJECTIVE: To compare sera levels of CEA and CA19-9 and tissular expression of the CA19-9 and to correlate these with morphological features of the colorectal carcinoma. METHODS: Forty five patients with colorectal carcinoma underwent surgical treatment following measurement of pre-operative levels of CA19-9 and CEA. Sera levels of CEA = 5.0ng/ml and CA19-9 = 37UI were deemed high values. Evaluation of CA19-9 immunoexpression in neoplastic tissue was carried through by means of immunohistochemical study with monoclonal antibody anti-CA19-9. The intensity of expression of CA19-9 in neoplastic areas was semi-quantified in each area of tumor differentiation into mild(+/+++), moderate(++/+++), intense(+++/+++) or absent. RESULTS: Sera CA19-9 values were progressively higher in the presence of elevated CA19-9 immunoexpression in colorectal carcinoma tissue, although not significant (p=0.06). Increased sera CA19-9 levels were found to be associated with significantly elevated (p<0.001) sera CEA levels. Levels of sera CA19-9, tissular immunoexpression of CA19-9 and sera levels of CEA presented no significant association with morphological features of the colorectal carcinoma. CONCLUSION: Sera and tissular levels of the CA19-9 marker exhibited, each other, a directly proportional relationship. The morphological features of the neoplasia had no influence on sera CEA or CA19-9 levels or tissular immunoexpression of CA19-9.

Relationship between peripheral and mesenteric serum levels of CEA and CA 242 with staging and histopathological variables in colorectal adenocarcinoma / Níveis séricos periféricos e mesentéricos de CEA e CA 242, estadiamento e variáveis histopatológicas no adenocarcinoma colorretal

PURPOSE: To compare histopathological variables and staging in colorectal adenocarcinoma cases with CEA and CA 242 in peripheral and mesenteric blood. METHODS: In 169 individuals underwent surgery for colorectal cancer, CEA and CA 242 were analyzed and compared to mesenteric and peripheral blood and correlated with macroscopic tumor's morphology and size, degree of cell differentiation, venous, neural and lymphatic involvement and TNM classification. RESULTS: There was a difference between the mesenteric (M) and peripheral (P) serum levels of CEA (p=0.020). Higher levels of markers were correlated with venous invasion CEA (P) p=0.013, CEA (M) p=0.05, CA 242 (M) p=0.005 and CA 242 (P) p=0.038; with advanced staging CEA (P) < CEA (M) (p < 0.05); CA 242 (P) < CA 242 (M) (p < 0.05); and with greater dimensions CEA (P) < CEA (M) (p < 0.001); CA 242 (P) < CA 242 (M) (p < 0.001). CA 242 became higher with neural invasion (P): p=0.014, (M): p=0.003). CONCLUSIONS: There were higher mesenteric than peripheral levels of CEA. Both mesenteric and peripheral levels of CEA and CA 242 were higher in neoplasm with venous involvement, greater diameter and advanced stages. There was a correlation between CA 242 and neural invasion.

OBJETIVO: Comparar variáveis histopatológicas e graus de estadiamento do adenocarcinoma colorretal com níveis sanguíneos periféricos e mesentéricos de CEA e CA-242. MÉTODOS: Em 169 doentes submetidos ao tratamento cirúrgico por adenocarcinoma colorretal, CEA e CA-242 foram analisados e comparados quanto aos níveis sanguíneos periféricos e mesentéricos e correlacionados com o tamanho e a morfologia macroscópica do tumor, grau de diferenciação celular, invasões venosa, linfática, neural e a classificação TNM. RESULTADOS: Verificou-se diferença significante entre o nível sérico mesentérico e periférico de CEA (p= 0,02). Níveis séricos mais elevados dos marcadores foram observados e correlacionados com invasão venosa, CEA (P) p=0,013, CEA(M), p=0,05, CA-242 (M) p=0,005 e CA-242 (P) p=0,038. Grau de estadiamento TNM avançado foi associado com CEA(P) < CEA(M) p<0,05, CA-242(P) < CA-242(M) p<0,05. Nas maiores dimensões tumorais constatou-se CEA(P) < CEA(M) p=0,001 e CA 242 (P) < CA 242 (M) (p < 0.001). O CA 242 periférico e mesentérico aumentados associaram-se com a invasão neural, p=0.014 e p=0.003, respectivamente. CONCLUSÕES: O nível sérico mesentérico de CEA é superior ao nível sérico periférico. Os níveis séricos mesentéricos e periféricos do CEA e do CA-242 são mais elevados no adenocarcinoma com invasão venosa, de maior diâmetro e de estadios avançados. Existe uma associação entre o nível sérico do Ca-242 e a invasão neural.

Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals

We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the å4/å4 genotype (6 percent) was present only in controls. The patients had reduced levels (mean ± SD) of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 ± 49.5 and 116.1 ± 43.1 mg/dL, respectively) compared to controls (204.2 ± 55.6, P = 0.135 and 134.7 ± 50.8 mg/dL; P = 0.330, respectively) indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low- and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014). There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P < 0.010). Moreover, a higher rate of hypertension and overweight was observed in controls (P < 0.002). In conclusion, the presence of the å4/å4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.

Persistent high postoperative carcinoembryonic antigen in colorectal cancer patients- is it important?

INTRODUCTION: Evaluation of pre- and postoperative serum CEA levels together has seldom been assessed for the prognosis of colorectal cancer (CRC). OBJECTIVE: To concurrently evaluate pre- and postoperative CEA as factors of relapse and survival. METHODS: The study consisted of 114 patients who had undergone surgery from February 2002 to June 2006 for CRC. All patients were classified into four groups according to their pre- and postoperative CEA levels. Data obtained for clinicopathologic parameters, lymph node metastasis, stage, recurrence, and CEA levels were analyzed to determine their association with survival. Multivariate analysis by the Cox proportional hazard regression model was performed to identify the independent prognostic factors associated with survival. RESULTS: Postoperative serum CEA levels remained high in Group 3 (n = 32). Nineteen patients (59.3 percent) demonstrated a detectable cause for persistent high CEA levels, while the reasons for those in the other thirteen patients (40.6 percent) remained obscure. Abnormal preoperative CEA levels significantly correlated with the depth of tumor invasion, lymph node metastasis, TNM stage, and recurrence (p < 0.05). Abnormal postoperative CEA levels were significantly related to the depth of tumor invasion, TNM stage, and postoperative relapse (p<0.05). Patients in Group 3 demonstrated the worst survival rate. Abnormal postoperative CEA levels, lymph node metastasis, and location of the tumor were independent prognostic factors for survival. CONCLUSION: The survival of patients with high postoperative CEA levels due to unknown reasons may be extended if they are exhaustively tested with sensitive diagnostic methods and treated at an early stage.

CEA preoperatorio como factor pronóstico en cáncer de colon y recto: análisis de 532 pacientes / Preoperative carcinoembriogenic antigen as prognostic factor in colorectal carcinoma

Antecedentes: La relevancia del antígeno carcinoembrionario (CEA) preoperatorio como factor pronóstico en el cáncer de colon y recto (CCR) es controversial. El objetivo de este estudio es analizar el valor del CEA preoperatorio como factor pronóstico independiente en el CCR. Pacientes y método: Se trata de 532 pacientes (54 por ciento mujeres) con un promedio de edad de 64,5 años (extremos 21-92). Para la etapificación de los tumores se usó la clasificación de la AJCC, conocida como TNM 1997. Las curvas de sobrevida fueron estimadas según el método de Kaplan-Meier. Para comparar las curvas de sobrevida se empleó el test log-rank. Para determinar los factores pronósticos más relevantes en el análisis multivariado se utilizó el modelo de regresión de Cox. Resultados: El CEA preoperatorio promedio en esta serie fue 21,42 ng/ml (desviación estándar (DE)= 70,76; extremos 0,1-840) y resultó mayor de 5 ng/ml en el 38 por ciento de los casos. Globalmente considerado, hubo una fuerte asociación entre el CEA preoperatorio y el estadio (p<0.0001). El seguimiento promedio de esta serie es de 49,3 meses (extremos 2-186). En el análisis multivariado la localización (recto; p<0.0001), el compromiso linfonodal (p<0.0001) y el CEA preoperatorio (p=0.002) se revelan como variables independientes con gran impacto en la sobrevida. Al introducir en el modelo de regresión de Cox el estadio según el TNM, se observó una diferencia estadísticamente significativa en la sobrevida sólo en los tumores del recto (RD=2.02; 95 por ciento IC= 1,35-3,03; p<0.0001) y en los estadios III (RD=4,19; 95 por ciento IC=1,08-16,24; p=0.038) y IV (RD=30,36; 95 por ciento IC=8,39-109.81; p<0.0001). Conclusión: El CEA preoperatorio refleja en buena medida la extensión del CCR y es un factor pronóstico relevante junto a la localización del tumor y del compromiso de los linfonodos. La fuerte asociación entre CEA preoperatorio y estadio determina que el CEA sea un factor pronóstico de menor potencia que...

Background: The real usefulness of preoperative carcinoembrionic antigen (CEA) as prognostic factor in colorectal cancer is not clearly defined. Aim: To assess the prognostic value of CEA in colorectal cancer. Material and methods: Follow up, during 2 to 186 months, of 532 patients aged 21 to 92years (54 percent females) operated for a colorectal cancer and in whom a preoperative determination of CEA was available. Tumor staging was done using the American Joint Committee on Cancer classification. Survival was determined using Ufe tables. A Cox regression model was used to determine relevant prognostic factors. Results: Mean preoperative CEA was 21.4 +/- 70.7 ng/ml and was over 5 ng/ml in 38 percent of patients. There was a strong association between CEA and tumor stage. Multivariate analysis disclosed location (rectum), lymph node involvement and preoperative CEA as independent prognostic factors. If TNM tumor stage is introduced in the Cox model, a significant difference in survival among patients with abnormal CEA values, is observed for rectal tumors with a Odds ratio of 2.02 and 95 percent confidence intervals (Cl) of 1.35-3.03, for stage III tumors, with an odds ratio of 4.19 (95 percent Cl 10.8-16.24) and for stage IV tumors, with an odds ratio of 30.36 (95 percent Cl 8.39-109.8). Conclusions: Preoperative CEA and the extension of colorectal tumors are independent prognostic factors for survival. The strong association between tumor stage and CEA values, determines that the latter outweigh the former as prognostic factor.

Detección de micrometástasis por RT-PCR de citokeratina 20 y su correlación con la sobrevida global en pacientes portadores de cáncer colorrectal / Cytokeratin 20 as a marker of tumor progression or dissemination in patients with colorectal cancer

Background: Colorectal cancer relapses or metastasizes in 30 percent of cases. Cytokeratin 20 is present in 95 percent of colorectal tumors and their metastases and could be used as a marker to detect tumor cells. Aim: To assess the usefulness and prognostic value of peripheral blood and bone marrow cytokeratin 20 determinations in patients with colorectal cancer. Material and methods: Blood and bone marrow samples were obtained from 56 patients with colorectal cancer aged 26 to 77 years (31 females) before surgical procedure. They were followed for a mean of 22 months (range 2.9 to 72 months) after surgery. Blood and bone marrow from 45 patients without cancer and 35 healthy subjects were used as negative controls. Messenger RNA expression of cytokeratin 20 was studied by real time and nested polymerase chain reaction. Results: Cytokeratin 20 was detected in 6 percent of controls and 41 percent of patients. There was no relation between cytokeratin 20 expression and age, gender, overall survival, tumor relapse, progression, localization or stage. Conclusions: Cytokeratin 20 determination is not useful as a marker of tumor progression or dissemination in patients with colorectal cancer.

Serum concentrations of fatty acids and colorectal adenoma risk: a case-control study in Japan.

BACKGROUND: Epidemiologic studies of n-3 fatty acids (FAs) and risk of colorectal cancer have generated inconsistent results, and relations with precursor colorectal adenomas (CRA) have not been evaluated in detail. We here focused on possible associations of serum FAs with CRA in the Japanese population. METHODS: We conducted a case-control study of 203 asymptomatic CRA cases (148 men, 55 women) and 179 healthy controls (67 men, 112 women) during 1997-2003 in Nagoya, Japan. Baseline information was obtained using a lifestyle questionnaire and serum FA levels were measured by gas chromatography. RESULTS: A non-significant inverse association with CRA was observed for eicosapentaenoic acid (EPA) among women. Moreover, the concentrations of docosahexaenoeic acid (DHA), a major component of n-3 highly-unsaturated FAs (HUFAs), were significantly lower in cases in both sexes. In addition, serum concentrations of total FAs, saturated FAs (SFAs) and mono-unsaturated FAs (MUFAs) had strong positive links with CRA risk. In contrast, arachidonic acid (AA) and DHA were inversely related, with 66% and 59% risk reduction, respectively. Ratios of SFAs/n-3 PUFAs and SFAs/n-3 HUFAs exhibited significant positive relations with CRA risk but there was no clear link with n-6 PUFAs/n-3 PUFAs. CONCLUSIONS: Our findings suggest a promoting influence of SFAs and MUFAs along with a protective effect of DHA on CRA risk. However, further research is needed to investigate the observed discrepancy with the generally accepted roles of the AA cascade in carcinogenesis.

C-Reactive Protein Level and Colorectal Adenoma / 대한소화기학회지

BACKGROUND/AIMS: Recent studies implicated inflammation playing an important role in the occurrence and advancement of colorectal cancer. Colorectal adenoma as the representative precursor lesion of colorectal cancer has meaningful association with inflammation. Accordingly, the purpose of this study was to evaluate the association between serum C-reactive protein (CRP) levels and the risk of colorectal adenoma METHODS: This study was undertaken on 5,487 subjects (3,478 men and 2,009 women) who underwent colonoscopy at the Health Promotion Center in Kangbuk Samsung Hospital and Samsung Medical Center. The subjects were allocated into 3,505 normal control subjects and 1,982 patients with colorectal adenoma. The mean level of CRP was compared between the two groups, and the correlations with other variables were analyzed by multiple regression analysis. Also, the risk of colorectal adenoma according to CRP level and difference of CRP level according to the characteristics of adenomas were analyzed. RESULTS: There was no significant difference in serum CRP level between normal and colorectal adenoma group. After adjusting for the clinically significant variables of colorectal adenoma, multiple logistic regression analysis of the risk of colorectal adenoma according to the CRP level (3) and the CRP level according to characteristics of adenomas showed no significant difference. CONCLUSIONS: An inflammatory marker, CRP is not a risk factor for colorectal adenoma development.

Association of serum lipids and apolipoprotein E gene polymorphism with the risk of colorectal adenomas

To investigate the relationship of serum lipids and apolipoprotein [apoE] gene polymorphism to colorectal adenomas. This study took place in the Department of Gastroenterology, Renmin Hospital of Wuhan University, PR China from June 2003 to March 2005. Ninety-eight patients with colorectal adenomas and 40 healthy subjects were enrolled, and their serum levels of triglyceride [TG], total cholesterol [TC], high density lipoprotein cholesterol [HDL-C], and low density lipoprotein cholesterol [LDL-C] were determined. The apoE gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. Serum TC levels of colorectal adenomas group [5.32 +/- 0.85 mmol/L], distal colorectal adenomas group [5.58 +/- 0.63 mmol/L], and villous adenoma group [5.49 +/- 0.69 mmol/L] were higher than the control group [4.28 +/- 0.62 mmol/L, p=0.016], proximal colorectal adenomas group [4.82 +/- 0.58 mmol/L, p=0.038] and non-villous adenoma group [4.76 +/- 0.58 mmol/L, p=0.03]. Serum HDL-C levels of colorectal adenomas group [1.39 +/- 0.25 mmol/L] were lower than the control group [1.51 +/- 0.29 mmol/L] [p=0.035]. Serum lipids levels of each genotype in colorectal adenomas group were not statistically significant. Apolipoprotein E3/E4 genotypic frequency in colorectal adenomas group [7.1%] was lower than the control group [17.5%] [p=0.012]. The findings suggest that altered lipid metabolism may be differentially associated with colorectal adenomas and the persons with apoE E3/E4 genotype have lower risk suffering from colorectal adenomas than those with other genotypes

Concentration of total matrix metalloproteinase-2 in the serum of patients with colorectal cancer

The processes of basement membrane degradation and remodeling of extracellular matrix [ECM] involves proteolytlc enzymes called metalloproteinases. Among the numerous metalloproteinases enzymes of this group the key role is played by matrix metalloproteinase-2 [MMP-2]. The purpose of this study was to evaluate the concentration of soluble MMP-2 in serum of patients with colorectal cancer and the effect of surgical treatment on this parameter in the postoperative period as well as assessment whether MMP-2 serum concentration correlate with clinicopathological variables. We measured, prior to primary surgery and 4 weeks after surgery, the concentrations of MMP-2 in serum samples of 40 patients with colorectal cancer. Also the serum concentration of MMP-2 of 10 healthy volunteers was measured. The measurements were performed with enzyme linked immunosorbent assays [ELISA]. MMP-2 concentrations are higher in cancer patients than control [P < 0.001]. The levels of soluble MMP-2 in serum [median of the control cut-off limit] correlated with Dukes' stage [P = 0.03], grade P=0-04], and lymph node metastasis [P = 0.02]. No statistically significant correlation was found between the circulating MMP-2 and the other clinicopathological factors. Comparing the blood serum concentration of MMP-2 before and after operation reveals a significant decrease after radical surgery. Plasma concentration MMP-2 was correlated with clinical staging in colorectal cancer, and falling to the normal range following curative surgery