Prognostic value of carcinoembryonic antigen levels in transoperative peritoneal lavage in patients with gastric cancer / Valor prognóstico dos níveis transoperatórios de antígeno carcinoembriônico em lavagem peritoneal de pacientes com câncer gástrico

ABSTRACT Background: The carcinoembryonic antigen level in peritoneal lavage has been showing to be a reliable prognostic factor in gastric cancer. Aim: To identify any association between carcinoembryonic antigen level in peritoneal lavage, in gastric cancer patients, with mortality, peritoneal recurrence, tumor relapse or other prognostic factors. Methods: In total, 30 patients (22 men, 8 women; median age 66 years) with resectable gastric cancer (mainly stage III and IV) were studied. Carcinoembryonic antigen level in peritoneal lavage was detected at operation by immunocytochemical method and a level over 210 ng/g of protein was considered as positive. Results: There were detected 10 positive cases (33.3%) of plCEA levels. These levels were associated with mortality, RR: 2.1 (p=0.018); peritoneal recurrence, OR: 9.0 (p=0.015); and relapse or gastric cancer progression, OR: 27.0 (p=0.001). Conclusion: Increased levels of plCEA fairly predicts mortality, peritoneal recurrence tumor relapse or cancer progression.

RESUMO Racional: Os níveis do antígeno carcinoembriônico no lavado peritoneal têm sido demonstrados como possível fator prognóstico de recidiva e mortalidade em pacientes com câncer gástrico. Objetivos: Medir seus níveis em lavado peritoneal durante operação de ressecção de câncer gástrico e ver se eles aumentados estão relacionados com mortalidade, recorrência, recidiva e outros fatores prognósticos. Métodos: Foi realizado lavado peritoneal durante ressecções de câncer gástrico; os níveis do antígeno carcinoembriônico nesse lavado maiores ou iguais a 210 ng/g foram considerados aumentados ou positivos. Resultados: Foram estudados 30 pacientes, destes, 33,33 % apresentaram níveis aumentados, os quais foram fator de risco para mortalidade em seis meses OR: 8,5 (1,458-49,539) IC 95%, mortalidade geral RR: 2,111 (1,314-3,391) IC 95%, mortalidade devido à doença OR: 12 (1,885-76,376) IC 95%, recorrência peritoneal OR: 9 (1,325-61,138) IC 95%, e recidiva ou progressão da doença OR: 27 (2,705-269,460) IC 95%. Conclusões: Os níveis aumentados do antígeno carcinoembriônico no lavado peritoneal foram fatores de risco para mortalidade, recorrência peritoneal, recidiva e progressão da doença em pacientes com câncer gástrico.

Analysis of gene expression EGFR and KRAS, microRNA-21 and microRNA-203 in patients with colon and rectal cancer and correlation with clinical outcome and prognostic factors

Abstract Purpose: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in colon and rectal cancer samples, correlated with their age at diagnosis, histological subtype, value of pretreatment CEA, TNM staging and clinical outcome. Methods: Expression of genes and microRNAs by real time PCR in tumor and non-tumor samples obtained from surgical treatment of 50 patients. Results: An increased expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor samples was found. There was no statistically significant difference between the expression of these genes and microRNAs when compared to age at diagnosis and histological subtype. The EGFR gene showed higher expression in relation to the value of CEA diagnosis. The expression of microRNA-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission. Conclusions: The therapy of colon and rectum tumors based on microRNAs remains under investigation reserving huge potential for future applications and clinical interventions in conjunction with existing therapies. We expect, based on the exposed data, to stimulate the development of new therapeutic possibilities, making the treatment of these tumors more effective.

Estudio comparativo de dos métodos para la cuantificación del antígeno carcinoembrionario / Comparative study of two methods for carcinoembryonic antigen quantification / Estudo comparativo de dois métodos para a quantificação do antígeno carcinoembrionário

El antígeno carcinoembrionario (CEA) es una glicoproteína ampliamente utilizada como complemento del diagnóstico, monitoreo de tratamiento y evolución del cáncer colorrectal. El objetivo del presente trabajo fue realizar un análisis comparativo entre dos métodos para la determinación de CEA: electroquimioluminiscencia y quimioluminiscencia, en muestras de suero de 57 pacientes con diagnóstico de cáncer, principalmente colorrectal. Cuando se analizaron los datos totales se obtuvo una elevada correlación (r=0,9135, p<0,00001). Al realizar un corte de los resultados tomando como límite el valor de 4 ng/mL se observó que las mayores discrepancias entre métodos estuvieron en los valores considerados dentro del rango normal (r=0,5716, p<0,0014, n=29). Por el contrario, en concentraciones mayores al límite de corte, la correlación fue elevada (r=0,9453, p<0,00001, n=28). Estos resultados sugieren que, a diferencia de lo descripto por los fabricantes, los valores de CEA obtenidos por ambos métodos son comparables. La menor correlación observada en concentraciones inferiores a 4 ng/mL no sería tan relevante debido a que estos niveles se consideran dentro del rango de normalidad y, por lo tanto, su importancia desde el punto de vista clínico es relativa. Sin embargo, debido a que pueden detectarse con baja frecuencia diferencias individuales (atribuidas probablemente a diferencias en los epitopes detectados por cada método), para los casos con fuerte presunción clínica y un valor de CEA incongruente, se sugiere repetir la determinación por medio de otra metodología.

The carcinoembryonic antigen (CEA) is a glycoprotein widely employed in colorectal cancer, mainly as evolutive marker and as measure of therapy's ef-ficacy. The goal of this work was to perform a comparative study between two analytical methods to measure serum CEA levels: electrochemiluminescence (ECL) and chemilumines-cence (CL) in serum samples of 57 patients with diagnosis of cancer, mainly colorectal. On the whole, an elevated correlation between ECL and CL (r=0.9135; p<0.00001) was obtained. When data was analyzed with a cut-off value of 4 ng/mL, the main discrepancy between methods occurred in the range of normal values (r=0.5716; p<0.0014; n=29). On the contrary, in concentrations higher than the cut-off, the cor-relation was very high (r=0.9453; p<0.00001; n=28). These results suggest that, in spite of the reports of manufacturers, the CEA values obtained by both methods are comparable. The lower correlation observed in values below 4 ng/mL would not be significant because those values are in the normal range and, for that reason, their clinical importance is minor. However, due to the individual differences that could be detected in some patients (probably resulting from the differences in epitopes detected by each method), in cases with strong clinical evidence without concordance with the CEA result, it could be necessary to repeat the determination using another methodology.

O antígeno carcinoembrionário (CEA) é uma glicoproteína amplamente usada como complemento do diagnóstico, monitoração de tratamento e evolução do câncer colorretal. O objetivo deste trabalho foi realizar uma análise comparativa entre dois métodos para a detecção do CEA: eletroquimioluminescência e quimio-luminescência em amostras de soro de 57 pacientes com diagnóstico de câncer, principalmente colorretal. Quando analisados os dados totais, houve uma correlação elevada (r=0,9135, p<0,00001). Quando realizado um corte dos resultados tomando como valor limite 4 ng/mL, observou-se que as maiores diferenças entre ambos os métodos estiveram nos valores considerados dentro da faixa dos valores normais (r=0,5716, p<0,0014, n=29). No entanto, nas concentrações superiores respeito do limite de corte, a correlação foi elevada (r=0,9453, p<0,00001, n=28). Estes resultados sugerem que, comparado com o descrito pelos fabricantes, os valores de CEA obtidos por ambos os métodos são comparáveis. A menor correlação observada nas concentrações inferiores a 4 ng/mL não seria tão relevante devido a que estes níveis consideram-se dentro da faixa de normalidade e, portanto, sua importância, do ponto de vista clínico, é relativa. Contudo, devido a que podem ser detectados com baixa frequência diferenças individuais (atribuídas provavelmente a diferenças nos epitopos detectados por cada método), para os casos com forte suspeita clínica e um valor de CEA incongruente, sugere-se repetir a determinação através de outra metodologia.

Aportes de la ecografía endoscópica a las lesiones quísticas del páncreas / [Contributions of endoscopic ultrasound to pancreatic cystic lesions].

Cystic lesions of the pancreas are peculiar in relation to their diagnosis and treatment. The use of endoscopic ultrasonography (EUS) has provided better sensitivity and specificity to differentiate benign from malignant cysts, condition that provides an early diagnosis and an effective and definite treatment.

Levels of CEA and Ca 19 - 9 in the sera and peritoneal cavity in patients with gastric and pancreatic cancers / Níveis de CEA e Ca 19 - 9 em soro e cavidade peritoneal em pacientes com câncer do estômago e pâncreas

PURPOSE: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. METHODS: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. RESULTS: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. CONCLUSIONS: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal).

OBJETIVO: Os marcadores tumorais são substâncias encontradas no sangue e outros fluidos biológicos em pacientes com doenças oncológicas. São produzidos pelo próprio tumor ou ser resultado da interação entre o tumor e o organismo. Podem ser usados no seguimento de pacientes com câncer para identificar recidiva tumoral. Os níveis pré-tratamento têm valor prognóstico e podem sinalizar persistência de doença residual mínima após cirurgia radical.. MÉTODOS: Foram operados 52 pacientes com tumores do trato gastroinstestinal superior (32 com câncer do estômago e 20 do pâncreas). Amostras sanguineas foram colhidas no préoperatório e amostras peritoneais imediatamente após a laparotomia, antes de qualquer manipulação do tumor. Todas as amostras foram examinadas bioquímicamente e os resultados foram comparados entre si e em face ao progresso da doença. RESULTADOS: Os pacientes com câncer de estômago nos estadios I e II apresentaram níveis sanguineos mais elevados de ambos os marcadores tumorais do que no peritônio, mas a maioria dos valores encontrava-se dentro dos limites fisiológicos. Já nos estadios III e IV os níveis dos marcadores tumorais foram mais elevados no peritônio do que no sangue. O número de exames positivos aumentou de acordo com o estadio da doença. Nos estádios avançados, observou-se elevada variabilidade nos níveis de ambos os marcadores analisados no peritônio. Os doentes com carcinoma de pâncreas tiveram níveis de CEA semelhantes no sangue e no peritônio, mas os níveis peritoneais foram ligeiramente mais elevados nos estadios III e IV. Ca 19 - 9 foi muito mais sensível para o câncer do pâncreas. A porcentagem de exames positivos foi mais elevada no sangue, mas o níveis do Ca19-9 foram mais elevados no peritônio.A porcentagem de exames positivos também teve correlação com o estadio da doença. CONCLUSÕES: Os níveis de marcadores tumorais no sangue podem indicar inoperabilidade do tumor. No peritônio podem indicar o tipo de ressecção, especialmente nos doentes com câncer gástrico, e o risco de recidiva peritoneal precoce. A diferença entre os níveis no peritônio e sangue podem sinalizar a via de disseminação, hematogênica ou intra-peritoneal.

Treatment of patients with colorectal cancer at a public hospital in Porto Alegre

OBJECTIVE: The purpose of this study is to demonstrate the current picture of colorectal cancer in a public hospital of Rio Grande do Sul, focusing on aspects related to diagnosis, staging and surgical therapy addressed in these patients. METHODS: A descriptive and retrospective study that includes patients with colorectal cancer admitted to the Proctology Service of the Hospital Nossa Senhora da Conceição de Porto Alegre, from January 2009 to May 2011. RESULTS: This study investigated 61 patients, 65.6% were female. Their age ranged from 40 to 84 years. Colonoscopy was performed in 58 patients; 56.9% of them had over 50% impaired colon lumen. The carcinoembryonic antigen (CEA) was collected from 59 patients, 47.5% had CEA>5 ng/mL. Distant metastases were found in 23.3% of total 60 patients. Underwent surgical treatment 58 patients, of a curative intent was 84.5%. The presence of more than 12 lymph nodes per specimen was 73.1%. All 61 patients were classified as: Stage I (9.8%), Stage II (29.5%), Stage III (29.5%) and Stage IV (31.1%). CONCLUSION: The profile of the patients treated at our institution indicates disease in advanced stage; however, the methods employed have provided a curative surgical treatment in our oncology patients. (AU)

OBJETIVO: O objetivo do presente estudo é demonstrar o panorama atual do câncer colorretal em um hospital público da capital do Rio Grande do Sul, enfocando aspectos relacionados ao diagnóstico, estadiamento e terapêutica cirúrgica abordada nesses respectivos pacientes. MÉTODOS: Estudo descritivo e retrospectivo que inclui os pacientes com câncer colorretal internados pelo Serviço de Coloproctologia do Hospital Conceição durante o período de janeiro de 2009 a maio de 2011. RESULTADOS: Foram estudados 61 pacientes, 65,6% mulheres. A idade variou de 40 a 84 anos. Realizaram colonoscopia 58 pacientes, desses 56,9% apresentavam mais de 50% de comprometimento da luz do cólon. O antígeno carcinoembrionário (CEA) foi coletado em 59 pacientes, 47,5% apresentavam CEA>5 ng/mL. Metástases à distância foram encontradas em 23,3% do total de 60 pacientes avaliados. Foram submetidos a tratamento cirúrgico 58 pacientes, desses a intenção curativa foi em 84,5%. A presença de mais de 12 linfonodos por peça foi de 73,1%. Os 61 pacientes estudados foram estratificados como 9,8% estádio I, 29,5% estádio II, 29,5% estádio III e 31,1% estádio IV. CONCLUSÃO: O perfil dos pacientes tratados em nossa instituição é de doença avançada; entretanto, os métodos curativos empregados têm ido ao encontro de um tratamento cirúrgico oncológico adequado. (AU)

Clinicopathological Characteristics of Gastric Cancer and Survival Improvement by Surgical Treatment in the Elderly / 대한소화기학회지

BACKGROUND/AIMS: It has been known that elderly patients with gastric cancer show worse general condition and higher comorbidities. Therefore, few elderly patients undergo surgery. This study was designed to determine clinicopathological characteristics of gastric cancer in elderly patients and evaluate their survival improvements by the surgical treatment. METHODS: Gastric cancer patients, diagnosed at Ewha Womans University Mokdong Hospital between 2000 to 2004, were divided into two groups those aged > or =65 years vs. <65 years. Clinicopathological characteristics, incidence of postoperative complications, and survival time of patients in each group were analyzed. RESULTS: Total 370 patients were subjected and divided into the elderly and the younger group (55.4% vs. 44.6%). The elderly group showed higher incidences of hypertension and cardiovascular disease. Well differentiated adenocarcinoma was more frequently found in the elderly group (19.0% vs. 10.0%, p=0.025). There were no differences of operation time (242.6+/-70.7 vs. 257.3+/-83.8 min, p=0.115), postoperative hospital stays (15.8+/-10.6 vs. 14.7+/-9.8 days, p=0.361), and incidence of any complications (6.7% vs. 9.9%, p=0.309) between the two subgroups. The significant factors related with the elderly patient's survival were the tumor-node-metastasis (TNM) stage (stage I, hazard ratio [HR] 1.00; stage II, HR 1.28, 95% confidence interval [CI] 0.44-3.72; stage III, HR 4.06, 95% CI 2.08-7.92, stage IV, HR 9.78, 95% CI 4.97-19.26;p<0.001) and the treatment modality (laparoscopy, HR 1.00; open surgery, HR 3.90, 95% CI 2.43-6.26;p<0.001). The elderly patients who underwent gastric cancer surgery showed prolonged survival on TNM stage I, II, and III than those who were treated conservatively. CONCLUSIONS: In the elderly patients with gastric cancer, those who had received surgical treatments showed significantly higher survival rate than those who had treated conservatively. Therefore, aggressive surgical treatments should be seriously considered even for the elderly patients with gastric cancer.

Prognosis of colorectal cancer with liver metastasis: value of a prognostic index

The objective of the present study was to explore the factors related to the prognosis of colorectal cancer (CRC) and to establish a prognostic model for the selection of patients who might benefit from hepatic resection for metastatic CRC. A total of 293 patients undergoing liver resection for metastatic CRC (172 males and 80 females ranging in age from 26 to 80 years) were selected and clinical, pathological and outcome data were examined in this retrospective study. The prognostic index (PI) of the patients was calculated on the basis of results of multivariate analysis. Patients were stratified into different groups, with survival curves projected according to PI. The 1-, 3-, and 5-year overall survival rates were 58.3, 26.4, and 11.3 percent, respectively. Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor. Patients were classified into three groups according to PI, which differed significantly in survival rate (P < 0.05). The individual survival rate was evaluated based on PI. Resection of hepatic colorectal metastases may produce long-term survival and cure. The proposed PI was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups.

Morphofunctional malignancy grading is a valuable prognostic factor for colorectal cancer / Graduação morfofuncional de malignidade como valioso fator prognóstico para o câncer colorretal

CONTEXT: Novel strategies are needed to identify more efficient biomarkers to accurately diagnose prognose and improve the treatment outcome of colorectal cancer. OBJECTIVES: To analyze the functional and morphological features of colorectal cancer to identify the neoplastic patterns that affect patient survival. METHODS: Forty-five patients with colorectal cancer were followed for a minimum of 3 years. Blood levels of carcinoembryonic antigen (CEA) were measured by chemiluminescence and immunohistochemical analysis of tissue expression followed by computer-assisted image processing. Tumors were assigned to three morphofunctional classes. The morphofunctional classification was based on combination between histological differentiation and cell polarization. The functional characterization was based on the CEA cell polarization. The tissue polarization of CEA was classified in well-polarized, moderately polarized or nonpolarized cells. Morphofunctional staging was defined by the association between morphofunctional class (polarization and histological differentiation) and TNM by score given to each one classification. RESULTS: There was an association between increased CEA tissue expression and loss of histological differentiation (P = 0.01) or loss of polarization capacity (P = 0.03). There was a progressive increase in tissue CEA quantities in accordance with the proposed morphofunctional grading system. Plasma levels of CEA were increased in advanced tumor stages. Blood levels of CEA were increased in advanced morphofunctional stages (P = 0.001). There was a relationship between survival outcome and morphofunctional staging (P = 0.005). CONCLUSION: Morphofunctional staging is a valuable prognostic factor for colorectal cancer and it correlates with plasma CEA levels.

CONTEXTO: Novas estratégias são necessárias à identificação de marcadores que promovam precisão no diagnóstico, no prognóstico e melhorem o tratamento de pacientes com câncer colorretal. OBJETIVO: Analisar características funcionais e morfológicas do câncer colorretal para identificar padrões de neoplasia que modificam a sobrevida. MÉTODOS: Quarenta e cinco pacientes com adenocarcinoma colorretal foram seguidos por no mínimo 3 anos. Níveis séricos de antígeno carcinoembrionário (CEA) foram mensurados por quimioluminescência e a análise imunoistoquímica da expressão tecidual do antígeno por meio de processamento de imagem assistida por computador. Tumores foram divididos em três classes morfofuncionais. A classificação morfofuncional foi baseada na combinação entre grau histológico e polarização do CEA celular. A polarização do CEA foi classificada em bem polarizada, moderadamente polarizada e não-polarizada. O estádio morfofuncional foi definido pela associação entre as classes morfofuncionais (polarização e grau histopatológico) e pontuação dada a cada uma das classificações. RESULTADOS: Houve associação entre aumento de expressão de CEA tecidual e perda do grau de diferenciação (P = 0.01) ou perda da capacidade de polarização (P = 0.03). Houve aumento progressivo dos níveis de proteínas teciduais em acordo com o sistema de classificação morfofuncional proposto. Níveis plasmáticos de CEA estavam aumentados com a progressão dos estádios tumorais (P = 0.001). Houve relação entre sobrevida e estádio morfofuncional (P = 0.005). CONCLUSÃO: Estádio morfofuncional é um valioso fator prognóstico para o câncer colorretal e se correlaciona com níveis séricos de CEA.

Análisis multivariado de factores clínicos y anatomopatológicos que determinan una elevación del antígeno carcinoembrionario en pacientes con cáncer de colon / Multivariate analysis of clinical and anatomopathological factors that determine an elevation of carcinoembryonic antigen in patients with colon cancer

El antígeno carcinoembrionario (ACE) es una glicoproteína que se encuentra en el endodermo primitivo y está ausente en la mucosa normal del adulto. Es usado como marcador tumoral en cáncer de colon, pero su utilidad es discutida. OBJETIVO: Evaluar la asociación del ACE preoperatorio con variables anatomopatológicas y de etapificación según TNM. MATERIALES Y MÉTODOS: Se revisaron 41 fichas clínicas de pacientes atendidos por cáncer de colon durante el año 2007 en el Hospital Clínico San Borja-Arriarán. La concentración sérica del ACE fue determinada mediante la técnica de inmuno-enzimoanálisis de micropartículas. Se utilizó el programa STATA9 para el análisis estadístico y se consideró significativo un p < 0.05. RESULTADOS: No existen diferencias entre las distintas localizaciones del tumor, histología, grado de diferenciación celular e invasión perineural, vascular y linfática del tumor.Se encontraron diferencias significativas en la etapificación según TNM. Tumores T1 poseen niveles menores que tumores T4; compromiso ganglionar N1 tiene niveles mayores que N2; el estadio1 tiene niveles menores que el estadio 3 y 4. CONCLUSIONES: El nivel plasmático de ACE preoperatorio tiene mayor correspondencia con variables de etapificación y no tiene asociación con variables anatomopatológicas, demostrando su utilidad en el proceso de etapificación clínica prequirúrgica. Sin embargo, se requieren estudios dirigidos para comprender la ventaja de este marcador como instrumento de etapificación.

The carcinoembryonic antigen (CEA) is a glycoprotein found in the primitive endoderm and is absent in normal adult mucosa. It is used as a tumor marker in colon cancer, but its usefulness is discussed. OBJECTIVE: To evaluate the association of presurgical ACE levels and pathological variables according to TNM staging. MATERIALS AND METHODS: 41 medical records were reviewed of patients seen per colon cancer in 2007 at the Hospital Clínico San Borja-Arriarán. STATA9 was used for statistical analysis and we considered significant p <0.05. RESULTS: There were not differences between tumor sites, histology, grade of cell differentiation and perineural, vascular and lymphatic invasion of the tumor. We found significant differences in the presurgical CEA levels according to TNM staging. T1 tumors have levels lower than T4 tumors; N1 lymph node involvement has greater levels than N2; stage 1 has smaller levels than the stage 3 and 4. CONCLUTIONS: The level of presurgical plasma CEA has higher correlation with staging variables than pathological variables, demonstrating its usefulness in the clinical staging process. However, studies are required aimed to understand the advantage of this marker as a means of staging.

Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma / Valor prognóstico da distribuição do antígeno carcinoembriônico (CEA) no tecido neoplásico do carcinoma colorretal

CONTEXT: Carcinoembryonic antigen (CEA) can be detected in colorectal tumor tissue but its role in the survival of patients remains controversial. OBJECTIVE: To characterize the expression of tissue CEA using immunohistochemical staining in colorectal tumors and to analyze the relationship between this finding and preoperative plasmatic level of CEA, morphologic features and survival of patients operated with curative intent for colorectal carcinoma. METHOD: Forty-seven patients were included in the study: 18 (38.3 percent) males and 29 (61.7 percent) females, with a mean age of 67.8 ± 9.7 years (37 to 84 years). Immediately before laparotomy, pre-operative serum levels of CEA were obtained where normal levels were considered <2.5 ng/mL for non-smokers, and <5.0 ng/mL for smokers. CEA immunohistochemical studies were carried out using anti-human CEA monoclonal mouse antibody. The expression of immunostaining for each neoplasia was classified according to the pattern of CEA tissular distribution into apical or cytoplasmic. The variables considered for the statistical analysis were plasmatic preoperative CEA level, location of the lesion within the large intestine, lesion diameter, lymph node involvement, Duke's classification, vein invasion, grade of cellular differentiation, survival and pattern of CEA tissular distribution. The statistical models utilized were Spearman's correlation and the Mann-Whitney, Kruskal-Wallis and Student t tests. Patients' survival was analyzed using the Kaplan-Meier method. RESULTS: The mean preoperative CEA value was 15.4 ± 5.5 ng/mL (0.2 to 92.1 ng/mL). The neoplasm was located in the colon in 29 (61.7 percent) and in the rectum in 18 (38.3 percent) patients. Eight (17.0 percent) patients were classified as Duke's stage A, 22 (46.8 percent) as stage B and 17 (36.2 percent) as stage C. On immunohistochemical studies, the pattern of CEA tissular distribution was apical in 33 (70.2 percent) patients and cytoplasmic...

CONTEXTO: O antígeno carcinoembrionário (CEA) pode ser detectado no tecido do carcinoma colorretal, mas seu papel na sobrevivência dos doentes permanece controverso. OBJETIVO: Caracterizar a expressão do CEA tecidual com coloração imunoistoquímica na neoplasia colorretal e analisar a relação entre esse achado e os níveis plasmáticos pré-operatórios do CEA, aspectos morfológicos e a sobrevivência dos doentes operados com intenção curativa de carcinoma colorretal. MÉTODO: Quarenta e sete doentes foram incluídos neste estudo: 18 (38,3 por cento) homens e 29 (61,7 por cento) mulheres, com média de idade de 67,8 ± 9,7 anos (37 to 84 anos). Imediatamente antes da laparotomia, foram obtidos os níveis plasmáticos pré-operatórios do CEA. Níveis séricos pré-operatórios normais de CEA foram considerados < 2,5 ng/mL para não-fumantes e <5,0 ng/mL para fumantes. O estudo imunoistoquímico do CEA foi realizado utilizando anticorpo monoclonal de rato anti-CEA humano. A expressão da imunocoloração de cada neoplasia foi classificada de acordo com o padrão de distribuição tecidual do CEA em apical ou citoplasmática. As variáveis consideradas para a análise estatística foram os níveis plasmáticos pré-operatórios do CEA, localização da lesão no intestino grosso, diâmetro da lesão, comprometimento dos linfonodos, classificação de Dukes, invasão venosa, grau de diferenciação celular, sobrevivência e padrão da distribuição tecidual do CEA. Os modelos estatísticos utilizados foram correlação de Spearman, teste de Mann-Whitney, teste de Kruskal-Wallis e teste t de Student. A sobrevivência dos doentes foi analisada utilizando-se o método de Kaplan-Meier. RESULTADOS: O valor médio de CEA pré-operatório foi de 15,4 ± 5,5 ng/mL (0,2 a 92,1 ng/mL). A neoplasia estava localizada no colo em 29 (61,7 por cento) e no reto em 18 (38,3 por cento) doentes. Oito (17,0 por cento) doentes foram classificados como estádio A de Dukes, 22 (46,8 por cento) como estádio B e 17...

Utility of fibronectin in immuocytochemial differentiation of reactive mesothelial cells from metastatic malignant cells in serous effusions.

Cytological evaluation of serous effusions often poses difficulties to the pathologists. This study was designed to assess the utility of fibronectin as a mesothelial cell marker and evaluate its use along with carcinoembryonic antigen (CEA) as a short panel to aid in the differentiation of reactive mesothelial cells from metastatic adenocarcinoma cells in serous effusions. Forty serous effusion cases from clinically benign cases and forty from clinically malignant cases with a known primary were included in the study. After routine cytological evaluation, the cases were categorized as benign, suspicious and malignant. All the cases were studied for fibronectin and CEA immunostaining using APAAP technique. In the present study, fibronectin emerged as a 100% specific and 93.4% sensitive marker for mesothelial cells. CEA immunostaining was seen in 80% cases of metastatic adenocarcinoma in serous effusions. Mesothelial cells did not show any CEA positivity. Short panel of CEA and fibronectin aided in reaching a correct diagnosis in three out of five cytologically suspicious cases.

Evaluation of preoperative predictive values of serum CA15-3 and CEA within Sudanese women with breast cancer

Early detection of cancer comprises early diagnosis in symptomatic and screening of asymptomatic individuals. Our aim was to evaluate the significant values of carbohydrate antigen 15-3 [CA15-3] and/or Carcinoembryonic antigen [CEA] in women with breast cancer. This case control study was conducted in Khartoum Teaching Hospital, Khartoum, Sudan. Application of such measurement may be helpful within screening and early detection efforts in such a country like Sudan with poor resources. We examined by serological radioimmuno-assay methods, significant elevation of CA15-3 and CEA serum samples obtained from 100 women of whom 40% and 35% were patients with histopathologically confirmed breast cancer and benign breast lumps respectively and the remaining 25% were apparently healthy controls. Statistical analysis: Data were analyzed by using a computer SPSS program. Among the 75 patients with breast lumps, 33 [44%] and 31[37.3%] showed high CA15-3 and CEA levels respectively. Of the 40 carcinomas, high expressions of CA15-3 and CEA were found among 28[70%] and 24[60%] respectively. Notably, only 2[8%] of the controls showed lightly elevated CEA. The obtained Specificity of 85.7%, 80% and sensitivity of 70%, 60% for CA15-3 and CEA correspondingly, support the combined application of both markers in screening for breast cancer

Níveis dos marcadores CEA e CA 19-9 no soro e no lavado peritoneal na avaliação do comprometimento linfonodal do carcinoma gástrico / Levels of CEA and CA 19-9 markers in sera and peritoneal wash and the evaluation of lymph node involvement in gastric carcinoma

Introdução: A recidiva peritoneal precoce do carcinoma gástrico operado com intenção curativa constitui grande desafio para seu tratamento e prevenção. Objetivo: Analisar a relação entre os níveis do marcador tumoral CEA e CA 19-9 no sangue e no lavado peritoneal e o comprometimento linfonodal do carcinoma gástrico. Métodos: Foram estudados 46 doentes operados por carcinoma gástrico. Vinte e nove (63

) eram do sexo masculino e 17 (37

Levels of carcinoembryonic antigen and CA 19-9 in the sera and peritoneal washing of patients undergoing surgical treatment for gastric carcinoma / Níveis do antígeno carcinoembriônico e do CA 19-9 no soro e no lavado peritonial em doentes submetidos ao tratamento cirúrgico do carcinoma gástrico

BACKGROUND: Early peritoneal recurrence of gastric carcinoma following curative resection remains a great challenge in the treatment and prevention of this disease. AIM: To analyze the relationship between levels of tumor markers, carcinoembryonic antigen (CEA) and CA 19-9 in the sera and peritoneal washing, and anatomopathological aspects of the gastric carcinoma. METHODS: Of the 46 patients in the study, 29 (63.0 percent) were males and 17 (37.0 percent) females. Mean age was 63.6 ± 11.7 years (31 to 91 years). Peripheral venous blood samples were collected from the upper limb vein from both patient groups after anesthetic induction, in order to determine serum levels of CEA and CA 19-9. After the end of the procedure, 50 mL of physiologic solution was introduced into the bottom of the Douglas sack and a portion aspirated to determine CEA and CA 19-9 levels in the peritoneal washing. Levels of CEA and CA 19-9 in the sera and peritoneal washing were compared to the following variables: lesion diameter ≤4 cm or >4 cm, lymph node involvement, angiolymphatic invasion, depth of invasion into gastric wall, and initial or late stage. RESULTS: Sera CEA levels were significantly higher in patients with lesions >5 cm. CEA levels in the sera and peritoneal washing were significantly greater in patients with signet ring cell gastric carcinoma. In addition, levels of CEA in peripheral blood and peritoneal washing showed significant association with the degree of carcinoma penetration into the gastric wall, while sera CEA was significantly higher in patients at more advanced stages. There was no significant difference between sera and peritoneal CEA values regarding grade of differentiation. Patients with gastric lesions measuring > 5cm and more differentiated lesions had significantly higher sera CA 19-9 values. In patients with lymph nodes invasion by gastric carcinoma, CA 19-9 levels in peritoneal washing were significantly higher than in ...

RACIONAL: A recidiva peritonial precoce do carcinoma gástrico operado com intenção curativa continua sendo um grande desafio do seu tratamento e prevenção. OBJETIVO: Analisar a relação entre os níveis do marcador tumoral antígeno carcinoembriônico (CEA) e CA 19-9 no sangue e no lavado peritonial e os aspectos anatomopatológicos do carcinoma gástrico. MÉTODO: Dos 46 doentes do estudo, 29 (63,0 por cento) eram do sexo masculino e 17 (37,0 por cento) do feminino. A média de idade foi de 63,6 ± 11,7 anos (31 a 91 anos). Após a indução anestésica, o sangue venoso periférico foi coletado de veia do membro superior para a determinação do nível sérico do CEA e CA 19-9. Após o término do procedimento operatório foram derramados 50 mL de solução fisiológica no fundo de saco de Douglas, aspirada alíquota que foi encaminhada para a determinação do nível no lavado peritonial do CEA e CA 19-9. O nível do CEA e do CA 19-9 sérico e no lavado peritonial foram relacionados às seguintes variáveis: diâmetro da lesão ≤4 cm ou >4 cm, comprometimento linfonodal, invasão angiolifática, profundidade de invasão na parede gástrica e estádio inicial ou tardio. RESULTADOS: Em relação ao CEA, o nível sérico foi significantemente maior nos doentes com o diâmetro da lesão >5 cm. O nível de CEA sérico e no lavado peritonial foi significantemente maior nos doentes com carcinoma gástrico com células em anel de sinete. O nível de CEA no sangue periférico e no lavado peritonial mostrou relação significante com o nível de penetração do carcinoma na parede gástrica, e o CEA sérico foi significantemente mais elevado nos doentes com estádio mais avançados. Não houve diferença significante entre os valores do CEA sérico e peritonial nos carcinomas mais diferenciados em relação aos menos diferenciados. No tocante ao CA 19-9, os enfermos com lesões gástricas com diâmetro >5 cm e mais diferenciadas exibiram valores séricos de CA 19-9 significantemente maiores. Nos doentes ...

O valor da dosagem do antígeno carcinoembrionário no diagnóstico diferencial entre derrame pleural neoplásico e tuberculoso / Carcinoembrionic antigen levels value in the differential diagnosis betwen neoplasic and tuberculous pleural effusion

Objetivos: Este trabalho objetiva avaliar o valor do antíge­no carcinoembrionário (CEA) no diagnóstico diferencial entre derrame pleural neoplásico e tuberculoso. Métodos: Com o intuito de determinar o ponto discrimi­nante (ponto de corte) da dosagem do CEA nestes dois tipos de derrames, foram estudados 106 pacientes com derrame pleural, atendidos na Fundação Centro de Controle de Oncologia do Amazonas (FCECON) e Hospital Universitário Getúlio Var­gas. A etiologia da doença foi confirmada por métodos histoló­gicos, citológicos e microbiológicos. Deste total, 28 pacientes foram retirados do protocolo por não se enquadrarem no diag­nóstico de tuberculose ou neoplasia. Os estudos estatísticos foram realizados com o programa de estatística SPSS 13.0, com a aplicação da estatística não paramétrica de Mann-Whitney e análise discriminante. O alfa adotado foi de 5%, com um intervalo de confiança de 95%. Resultado: Na análise dos dados dividiu-se a população em estudo inicialmente em quatro grupos, constituídos por tuberculose confirmada, neoplasia confirmada, tuberculose pro­vável e neoplasia provável, posteriormente agrupados nos dois grupos principais: tuberculose e neoplasia. Ao final, 33 pacientes eram tuberculosos e 45 tinham neoplasia. A mediana da dosagem do CEA nos derrames tuberculosos foi de 0,95 ng/ml, enquanto nos pacientes com derrame neoplásico foi de 18,80 ng/ml. O ponto de corte encontrado foi de 11,5 ng/ml. Conclusão: O estudo mostrou que a dosagem do CEA e um fator importante no diagnóstico diferencial entre os derrames pleurais supracitados, sendo um meio menos invasivo no auxílio para o diagnóstico.

Histopathological characterization of a syngeneic orthotopic murine bladder cancer model

PURPOSE: We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line. MATERIALS AND METHODS: Bladder tumor implantation was achieved by intravesical instillation of 5 x 10(5) MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3). After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7), carcinoembrionic antigen (Dako-CEA), p53 and c-erbB2 oncoprotein (Her2/neu). RESULTS: Twenty-nine out of 30 animals (96.7 percent) developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g), 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model. CONCLUSIONS: High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

Establishment of Reference Intervals of Tumor Markers in Korean Adults / 대한진단검사의학회지

BACKGROUND: The sensitivity and specificity of tumor markers for detecting cancer could be significantly changed by the reference intervals of tumor markers. We established reference intervals of tumor markers in Korean adults and evaluated its importance, since the reference intervals recommended by the manufacturers were determined in the Caucasian population and have sometimes been adopted without verification. METHODS: We established the reference intervals of alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)125, carbohydrate antigen (CA)19-9, total prostate specific antigen (TPSA), cytokeratin fragment (Cyfra)21-1, and neuron specific enolase (NSE) according to the CLSI guideline in a maximum number of 1,364 healthy adults aged 20-60 yrs who visited a health promotion center from January to February 2007. RESULTS: Reference intervals of all tumor markers except for AFP were not in agreement with those recommended by the manufacturers. Reference intervals of CEA, TPSA, CA19-9, CA125, and Cyfra21-1 were age dependent. The mean reference values of NSE, CA125, and CEA were statistically different according to gender (11.72 vs 10.78 ng/mL), menopause status (18.89 vs 12.62 U/mL), and smoking status (2.60 vs 2.12 vs 1.80 ng/mL for smokers, past smokers, and non-smokers, respectively),respectively. CONCLUSIONS: With the verification and establishment of reference intervals of tumor markers in a Korean local population, we found the reference intervals significantly different by either age, gender, smoking or menopause status.

Avaliação dos valores sérico e pleural dos marcadores tumorais CEA, CYFRA21-1 e CA 15-3 em portadores de derrame pleural / Evaluation of serum and pleural levels of the tumor markers CEA, CYFRA21-1 and CA 15-3 in patients with pleural effusion

OBJETIVO: Dosar os marcadores tumorais antígeno carcinoembrionário (CEA), fragmento da citoqueratina 19 (CYFRA21-1) e antígeno glicosídico associado a tumor 15-3 (CA 15-3) em sangue e líquido pleural de portadores de derrames pleurais benignos e malignos, avaliando a sensibilidade de cada um deles nesses fluidos. MÉTODOS: Avaliamos prospectivamente 85 pacientes com derrame pleural. O estudo do líquido pleural obedeceu a critérios determinados pela literatura. A dosagem dos marcadores foi realizada por eletroquimioluminescência. A sensibilidade foi determinada sob a condição de que a especificidade fosse > 90 por cento. RESULTADOS: Foram diagnosticados 36 casos malignos (42,4 por cento), 30 benignos (35,3 por cento); em 19 pacientes (22,3 por cento), o diagnóstico foi inconclusivo. Nos casos malignos, os valores de CEA e CYFRA21-1 foram maiores no líquido pleural do que no sangue, fato não observado para o CA 15-3. Nos casos benignos, os valores do CYFRA21-1 foram maiores no líquido pleural do que no soro, enquanto que para o CEA e o CA 15-3, ocorreu o oposto. Todos os marcadores apresentaram diferença significativa entre os casos malignos e benignos, em líquido pleural e soro. Foi encontrada sensibilidade para CEA, CYFRA21-1 e CA 15-3 no líquido pleural de 69,4 por cento, 69,4 por cento e 66,7 por cento, respectivamente e quando associados, foi 80,6 por cento. No soro, a sensibilidade foi 57,1, 71,4 e 48,6 por cento para CEA, CYFRA21-1 e CA 15-3, respectivamente, e quando associados, foi 77 por cento. CONCLUSÃO: Os resultados sugerem que a utilização desses marcadores pode ser útil na diferenciação entre derrames pleurais malignos e benignos.

OBJECTIVE: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15-3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. METHODS: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was > 90 percent. RESULTS: Of the 85 cases, 36 (42.4 percent) were malignant, 30 (35.3 percent) were benign, and the results were inconclusive in 19 (22.3 percent). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7 percent, respectively, and the combined sensitivity was 80.6 percent. In the blood, the sensitivity was 57.1 percent, 71.4 percent and 48.6 percent for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77 percent. CONCLUSION: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion.

Marcadores morfológicos de prognóstico no mesotelioma maligno: um estudo de 58 casos / Morphological aspects as prognostic factors in malignant mesothelioma: a study of 58 cases

OBJETIVO: Diversos marcadores têm se mostrados promissórios como preditores do diagnóstico e prognóstico do mesotelioma maligno (MM). MÉTODO: Mediante estudo morfométrico e inmunomarcação de componentes estromais (calretinina, CEA, Leu-M1 e trombomodulina) e nucleares (p53 e Ki-67), avaliamos a sobrevida após o diagnóstico de 58 pacientes com tumores malignos de pleura. RESULTADOS: O padrão histológico típico do mesotelioma maligno foi encontrado em 50 casos e o padrão atípico em 8 casos. Imunohistoquimicamente foram confirmados 40 casos como sendo mesoteliomas, 11 como adenocarcimonas e 7 casos do padrão atípico não puderam ser classificados. A análise multivariavel do Cox demonstrou a coexistência de um maior fator de risco de morte (476.2), nos pacientes com idade avançada, subtipo histológico bifásico e componentes de expressão nuclear. CONCLUSÃO: A calretinina foi o marcador inmunohistoquímico (IHQ) mais útil para o diagnóstico do mesotelioma e o CEA para o de adenocarcinoma. A quantificação por IHQ da trombomodulina foi fundamental na diferenciação do mesotelioma quando este foi positivo tanto para calretinina e como para o CEA. A informação prognostica mais valiosa foi a fornecida pela análise rotineira histopatológica do tipo histológico tumoral. Um ponto importante, divisor natural, foi a idade com uma media de 55 anos e 30.5 por cento de componentes nucleares de marcação IHQ, separando os pacientes em dois grupos: pacientes com uma sobrevivência curta contra pacientes com uma sobrevivência mais longa que a esperada. Assim, a análise histopatológica oferece uma arma poderosa e de elevado potencial para guiar no tratamento adjuvante de quimioterápicos após a retirada cirúrgica do mesotelioma.

OBJECTIVE: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). METHODS: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki-67), we evaluated post-diagnosis survival in 58 patients with MM. RESULTS: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. CONCLUSION: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5 percent immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma.