CEA as a prognostic index in colorectal cancer

INTRODUCTION: The carcinoembryonic antigen, CEA, is the tumor marker most used in colorectal patients, principally during follow up after radical surgery. High serum CEA level before surgery is often associated with worse prognosis, in some studies. OBJECTIVE: The purpose of this study was to evaluate the preoperative carcinoembryonic antigen levels (CEA) and the frequency of recurrence. MATERIAL AND METHODS: Eighty-three patients with colorectal cancer at Dukes stages A, B or C were evaluated retrospectively. The patients' follow up was at least two years or to death. CEA was detemined in serum by enzyme immunoassay (Sorin Biomedica), normal value 0-5ng/mI. RESULTS: Disease recurrence was observed in 32 patients (38.5%), 13 Dukes B and 19 Dukes C. Seventy five per cent of the patients with CEA higher than 10ng/ml relapsed and 80% of the patients without recurrence had normal CEA. Disease recurrence in patients with preoperative elevated CEA occurred during the first year of follow up in 56% of the patients. CONCLUSION: Although the tumor stage is today the most valuable prognostic variable in colorectal cancer, the preoperative CEA value can provide some additional information in the prognosis of the patient.INTRODUÇÃO: O antígeno carcinoembrionário, CEA é o marcador tumoral mais usado em pacientes com câncer colorretal, principalmente no acompanhamento clinico após ressecção cirúrgica do tumor. Níveis séricos elevados de CEA no pré-operatório são frequentemente associados, em alguns estudos, a pior prognóstico. OBJETIVO: Comparar os níveis séricos de CEA no pré-operatório e a frequência da recorrência no acompanhamento clinico. MATERIAL E MÉTODOS: Oitenta e três pacientes com câncer colorretal estadiados em Dukes A, B, e C foram avaliados retrospectivamente. Os pacientes foram acompanhados, por no mínimo dois anos ou até o óbito. O CEA sérico foi determinado por Elisa (Sorine Biomédicas, valor normal 0-5 ng/ml). RESULTADOS: A recorrência foi observada em 32 pacientes (38.5%), sendo 13 pacientes Dukes B e 19 Dukes C. Setenta e cinco por cento dos pacientes com CEA maior que 10ng/ml apresentaram recorrência e oitenta por cento dos pacientes sem recorrência tinham níveis séricos de CEA dentro do valor de normalidade. Nos pacientes com CEA elevado no pré-operatório e que desenvolveram recorrência, esta ocorreu no primeiro ano de acompanhamento em 56% dos pacientes. Dezesseis pacientes foram a óbito durante o acompanhamento, 11 destes tinham CEA sérico aumentado no pré-operatório. CONCLUSÃO: Embora, o estadiamento clinico seja a variável mais usada na avaliação do prognóstico, os valores de CEA no pré-operatório podem fornecer algumas informações adicionais sobre o prognóstico do doente.UNIFESP-EPM Department of OncologyUNIFESP, EPM, Department of OncologySciEL

¿Cuáles son los métodos más eficaces de valoración del estado nutricional en pacientes ambulatorios con cáncer gástrico y colorrectal?

Objective: To evaluate methods for the identification of nutrition risk and nutritional status in outpatients with colorectal (CRC) and gastric cancer (GC), and to compare the results to those obtained for patients already treated for these cancers.Methods: A cross-sectional study was conducted on 137 patients: group 1 (n = 75) consisting of patients with GC or CRC, and group 2 (n = 62) consisting of patients after treatment of GC or CRC under follow up, who were tumor free for a period longer than 3 months. Nutritional status was assessed in these patients using objective methods [body mass index (BMI), phase angle, serum albumin]; nutritional screening tools [Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), Nutritional Risk Index (NRI)], and subjective assessment [Patient-Generated Subjective Global Assessment (PG-SGA)]. the sensitivity and specificity of each method was calculated in relation to the PG-SGA used as gold standard.Results: One hundred thirty seven patients participated in the study. Stage IV cancer patients were more common in group 1. There was no difference in BMI between groups (p = 0.67). Analysis of the association between methods of assessing nutritional status and PG-SGA showed that the nutritional screening tools provided more significant results (p < 0.05) than the objective methods in the two groups. PG-SGA detected the highest proportion of undernourished patients in group 1. the nutritional screening tools MUST, NRI and MST were more sensitive than the objective methods. Phase angle measurement was the most sensitive objective method in group 1.Conclusion: the nutritional screening tools showed the best association with PG-SGA and were also more sensitive than the objective methods. the results suggest the combination of MUST and PG-SGA for patients with cancer before and after treatment.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Oncol Grp, Div Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Oncol Grp, Div Gastroenterol, São Paulo, BrazilFAPESP: 10/19191-2Web of Scienc

Laminin concentration in ascites of patients with hepatic cirrhosis and peritoneal carcinomatosis

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 ± 0.5 vs 2.1 ± 0.4 µg/ml, mean ± SD, P 2.25 µg/ml showed 100% sensitivity and 73% specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de GastroenterologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de ImunologiaUNIFESP, EPM, Disciplina de GastroenterologiaUNIFESP, EPM, Disciplina de ImunologiaSciEL

CYP2E1 RsaI and 96-bp insertion genetic polymorphisms associated with risk for colorectal cancer

We investigated a possible association between alcoholism, cigarette smoking, obesity and CYP2E1 RsaI and 96-bp insertion genetic polymorphisms with risk for colorectal cancer (CRC). Patients with CRC (70 women and 61 men) were matched for gender and age to 206 healthy controls. the mean age of the two groups was 62 years. Meat intake, cigarette smoking and alcohol drinking were assessed using a specific frequency questionnaire. the body mass index was also calculated. DNA was extracted from peripheral blood; RsaI polymorphism genotypes were evaluated by PCR-RFLP and 96-bp insertion genetic polymorphisms were evaluated by specific primers. the distributions of CYP2E1 RsaI c1/c1, c1/c2 and c2/c2 genotypes were 90.2, 9.2 and 0.6%, respectively, in controls and 83.9, 13.7 and 2.4% in CRC cases. Allele c2 was associated with increased risk for CRC [odds ratio (OR) = 1.88, 95% confidence interval (95%CI) = 1.02-3.45]. the CYP2E1 RsaI c2/c2 genotype was associated with an increased risk for rectal cancer (OR = 3.23, 95% CI = 1.26-9.03). the 96-bp insertion was slightly more frequent in the CRC group (9.3 vs 11.4%, P = 0.19), especially in females (6.4 vs 11.5%, P = 0.34). Smoking, alcohol drinking or high intake of red meat and CYP2E1 polymorphisms were not associated with increased risk for CRC. the 96-bp insertion was marginally more frequent (P = 0.07) in undernourished CRC subjects. We concluded that the risk for CRC is higher among individuals with allele c2. the CYP2E1 RsaI c2/c2 genotype was associated with an increased risk for rectal cancer.Universidade Federal de São Paulo, Setor Oncol, Disciplina Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Setor Oncol, Disciplina Gastroenterol, São Paulo, BrazilWeb of Scienc

Establishment and Partial Characterization of an Epirubicin-Resistant Gastric Cancer Cell Line with Upregulated ABCB1

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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Med, Div Gastroenterol, São Paulo, BrazilUniv Nove de Julho, Coll Pharm, Dept Hlth, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Gastroenterol, São Paulo, BrazilWeb of Scienc

Influencia del estado nutritivo y la enfermedad sobre las concentraciones de adiponectina y TNF-α en pacientes con cáncer colorrectal

Background: the aim of this study was to evaluate the association between adiponectin and tumor necrosis factor-a (TNF-alpha) serum levels in colorectal cancer (CRC) patients and compare these levels to clinical stage and nutritional status.Methods: A total of 79 patients were enrolled in the study (39 with CRC and 40 in the control). Nutritional status was assessed by Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), and phase angle (PhA). Adiponectin and TNF-alpha serum concentrations were determined using an enzyme-linked immunosorbent assay.Results: Serum adiponectin levels were higher among CRC patients (p = 0.001). TNF-alpha serum levels were not significantly different between the groups, but patients with stage III or IV CRC had higher levels of TNF-alpha than those with lower stage disease (p = 0.037). the three tools used for the assessment of nutritional status (BMI, PhA, and PG-SGA) demonstrated that patients with a more severe nutritional deficit had higher adipocytokine levels, although these differences were significant only to TNF-alpha, when distributed PhA in tertiles.Conclusions: Adiponectin levels were higher among CRC patients. Although TNF-alpha serum levels from CRC patients did not differ significantly to the control group, CRC patients with stage III or IV had higher levels compared to those with stage I and II tumors. Nutritional status, as determined by BMI, PhA, and PG-SGA, demonstrated that patients with a greatest nutritional deficit, had higher levels of adipocytokines; however, these differences were significant only for TNF-alpha, when distributed PhA in tertiles.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Escola Paulista Med, Dept Med, Div Gastroenterol, Oncol Grp, BR-04023 São Paulo, BrazilDept Physiol, São Paulo, BrazilEscola Paulista Med, Dept Med, Div Gastroenterol, Oncol Grp, BR-04023 São Paulo, BrazilFAPESP: 10/19191-2Web of Scienc

Association between ABCB1 Immunohistochemical Expression and Overall Survival in Gastric Cancer Patients

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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Div Gastroenterol, Dept Med, UNIFESP, São Paulo, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Pathol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Div Gastroenterol, Dept Med, UNIFESP, São Paulo, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Pathol, São Paulo, SP, BrazilFAPESP: 10.19715-1Web of Scienc

Metástase cerebral hemorrágica como manifestação inicial de um carcinoma hepatocelular: relato de caso

We report herein a rare instance in which a patient presented with a hemorrhagic cerebral metastasis as the initial manifestation of a hepatocellular carcinoma (HCC). A few cases of cerebral metastasis from HCC have been reported in the literature, mainly from eastern countries. This is the first report from South America of a cerebral metastasis from hepatocellular carcinoma.Relatamos o caso de um paciente que teve como primeira manifestação de um carcinoma hepatocelular uma metástase cerebral hemorrágica, evento raro na literatura. Os poucos casos de metástase cerebral por carcinoma hepatocelular foram relatados em países do Oriente, onde o tumor é mais comum. Este é o primeiro relato de metástase cerebral de carcinoma hepatocelular da América do Sul.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Immunoexpression of cyclooxygenase-1 and -2 in ulcerative colitis

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29% of the cases and in inflammatory cells in 43%. COX-2 positivity in epithelial and inflammatory cells was found in 69% of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPM, Depto. de PatologiaUNIFESP, EPMSciEL

RNA Interference: a Promising Therapy for Gastric Cancer

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.Universidade Federal de São Paulo, Dept Med, Div Gastroenterol, São Paulo, BrazilUniv Nove Julho, Dept Hlth, Coll Pharm, São Paulo, BrazilEstadual Univ Santa Cruz, Dept Biol Sci, Santa Cruz, BA, BrazilUniversidade Federal de São Paulo, Dept Med, Div Gastroenterol, São Paulo, BrazilWeb of Scienc