Preoperative differentiation of benign and malignant non-epithelial ovarian tumors: clinical features and tumor markers / Diferenciação pré-operatória de tumores ovarianos não epiteliais benignos e malignos: características clínicas e marcadores tumorais

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Resumo Objetivo Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. Métodos Cento e dezenovemulheres consecutivas comtumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. Resultados Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estromamalignos foram tratadas comcirurgia preservadora de fertilidade. Cinco (71,4%)mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. Conclusão Os tumores de ovário não epiteliais foram benignos namaioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico préoperatório desses tumores.

Comparison of serum NEDD-9, CA 15-3, and CEA levels and PET metabolic parameters in breast cancer patients with 18 F-FDG PET / CT

SUMMARY OBJECTIVE Analyze the over expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) deregulated associated with a poor prognosis in various carcinomas. Our objective was to investigate the relationship between the levels of NEDD-9, CA 15-3, and CEA and PET (SUVmax, MTV40, TLG40) with the clinical parameters of patients with breast cancer (BC). METHODS One hundred and eleven patients (82 BC patients who underwent 18F-FDG PET/CT and 29 healthy controls) were evaluated. SUVmax, MTV, and TLG of the primary tumor were compared with the molecular and histopathological subtypes. 18F-FDG, MTV, and TLG were evaluated based on the clinical data, i.e., nodal involvement, distant metastasis, ER and PR status, Ki-67, serum levels of NEDD-9, CA15-3, and CEA. We compared the NEDD-9 in the BC and healthy control groups. RESULTS The mean ± SD of SUVmax in the 82 patients was 13.0 ± 8.6. A statistically significant relationship (p = 0.022) was found between the molecular subtypes and 18F-FDG uptake. The relationship between 18F-FDG uptake and TLG measured in patients <50 years, ER-PR negativity, and HER2 positivity were statistically significant (p=0.015, 0.007, 0.046, and 0.001, respectively). MTV40, TLG40, and CA 15-3 in metastatic patients were statistically significant (p=0.004, 0.005, and 0.003, respectively). NEDD-9 in the BC group was significantly higher than in the healthy group (p=0.017). There was a positive correlation between SUVmax and Ki67 and CA 15-3; MTV40 and CEA; CA 15-3, CEA, SUVmax, and MTV40; a negative correlation was found between CEA, TLG40, and age. CONCLUSION The use of SUVmax, MTV40, and TLG40 parameters with NEDD-9 and tumor markers has been shown to provide a high diagnostic, predictive, and prognostic value for the management of BC. This is considered to be the basis of interventions focused on the treatment objectives related to NEDD-9.

RESUMO OBJETIVO Analisar a associação da superrexpressão das células NEDD-9 ao prognóstico negativo em vários tipos de carcinoma. Nosso objetivo foi investigar a relação entre os níveis de NEDD-9, CA 15-3 e CEA e PET (SUVmax, MTV40, TLG) e os parâmetros clínicos em pacientes com câncer de mama (CM). MÉTODOS Cento e onze pacientes (82 pacientes de CM submetidos a 18F-FDG PET/TC e 29 controles saudáveis) foram avaliados. SUVmax, MTV, e TLG do tumor primário foram comparados nos subtipos molecular e histopatológico. A captação de 18F-FDG, MTV, e TLG foi avaliada com base em dados clínicos (envolvimento nodal, metástase distante, status de ER e PR, Ki-67, níveis séricos de NEDD-9, CA15-3 e CEA). Foi comparada a NEDD-9 do grupo de CM e o controle saudável. RESULTADOS A média ± DP de SUVmax de 82 pacientes foi de 13,0 ± 8,6. Uma relação estatisticamente significativa (p=0,022) foi encontrada entre subtipos moleculares e captação de 18F-FDG. A relação entre captação de 18F-FDG e TLG medida em pacientes com idade <50 anos, ER-PR negativo e HER2 positivo foi estatisticamente significativa (p=0,015; 0,007; 0,046; e 0,001, respectivamente). MTV40, TLG40 e CA 15-3 em pacientes metastáticos foram estatisticamente significantes (p=0,004, 0,005 e 0,003, respectivamente). NEDD-9 no grupo BC foi significativamente maior do que no grupo saudável (p=0,017). Uma correlação positiva foi encontrada entre SUVmax e Ki67 e CA 15-3; MTV40 e CEA; CA 15-3, CEA, SUVmax e MTV40; uma correlação negativa foi encontrada entre CEA, TLG40 e idade. CONCLUSÃO O uso dos parâmetros SUVmax, MTV40 e TLG40 com NEDD-9 e marcadores tumorais demonstrou um alto valor diagnóstico, preditivo e prognóstico para o manejo do CM. Isso é considerado a base para intervenções focadas nos objetivos de tratamento relacionados às NEDD9.

Rendimiento diagnóstico de marcadores tumorales séricos convencionales en pacientes con sospecha clínica de cáncer primario metastásico a hígado / Conventional serum tumor markers in liver cancer. Retrospective analysis of 118 patients

Background: Conventional serum tumor markers (CSTM) are widely used for monitoring patients with cancer. However, their usefulness as a diagnostic tool is controversial in primary or metastatic liver cancer (PMLC). Aim: To evaluate the diagnostic performance of the most commonly requested CSTM in the diagnostic approach of PMLC. Material and Methods: Review of medical records of patients aged over 18 years with a liver biopsy, attended from 2005 to 2017 in a tertiary hospital and a regional cancer center in Colombia. The results of liver biopsies were compared with tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 125 and prostate specific antigen (PSA) using a receiver operating characteristic (ROC) curve analysis. Results: We reviewed 2063 medical records and retrieved 118 eligible patients (59 cases and 59 controls, 70% males). Thirty percent had obstructive jaundice. There was heterogeneity in the amount of tumor markers requested according to medical criteria. Only CA 19-9 showed discriminative capacity (> 17.6 U/m), with a cut-off point lower than that reported in the literature and a sensitivity of 69.5%, specificity of 91.6%, a positive likelihood ratio (LR) of 8.32, and a negative LR of 0.33. Conclusions: Except for CA 19-9, tumor markers were not useful for the initial diagnostic approach in patients with suspected primary or metastatic malignant liver tumors.

The diagnostic value of FNDC5/irisin in renal cell cancer

ABSTRACT Purposes: The aim of this study was to determine the diagnostic significance of fibronectin type III domain containing protein 5 (FNDC5)/Irisin levels in the sera of patients with renal cell cancer. Materials and Methods: In the study, 48 individuals were evaluated. The patient group included 23 subjects diagnosed with renal tumor, and the control group of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected and serum FNDC5/Irisin and carcinoembryonic antigen (CEA) levels were determined using enzyme-linked immunosorbent assay (ELISA). Results: FNDC5/irisin and CEA levels in renal cancer patients were significantly higher compared with the control group (p=0.0001, p=0.009, respectively). Also, FNDC5 levels was more sensitive and specific than CEA levels. The best cut-off points for FNDC5/irisin were >105pg/mL and CEA were >2.67ng/mL for renal cancer. Conclusions: FNDC5/Irisin may be used as a diagnostic biomarker for renal cancer.

Comparative evaluation of oncologic outcomes in colon cancer

PURPOSE: In this paper we report clinical variables on colon cancer series. Oncological outcomes were compared to low-income and high-income countries. METHODS: We analysed a prospective database of 51 colon cancer patients submitted to primary tumor resection between 2010 and 2011, showing clinical variables and oncologic outcomes. RESULTS: R0 resection obtained in 80.4%, 21.6% of patients was TNM stage IV, and only 13.7% showed TNM stage I. Disease-free survival was 32 months, overall survival was 46 months, and the tumoral recurrence rate was 9.8%. Univariate analysis showed association of serum CEA levels ≥ 5 ng/dl (p= 0.004), presence of metastasis at diagnosis (p= 0.012), compromised surgical margins (p < 0.001) and poorer tumor differentiation (p= 0.041) to death. Multivariate analysis identified compromised surgical margins as an independent risk factor for death due to colon cancer (P=0.003; odds ratio=0.36; 95% confidence interval=0.004-0.33). Nowadays, 62.7% of patients are alive. CONCLUSION: Recurrence rate, disease-free survival and overall survival was similar to those observed in more developed countries. Serum CEA levels ≥ 5 ng/dl, the presence of metastasis at diagnosis, compromised surgical margins and poorer tumor differentiation were associated with death. A compromised surgical margin was the only independent risk factor for death.

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.

Postoperative Carcinoembryonic Antigen as a Complementary Tumor Marker of Carbohydrate Antigen 19-9 in Pancreatic Ductal Adenocarcinoma

The role of carcinoembryonic antigen (CEA) in pancreatic cancer remains poorly understood. Therefore, this study aimed to determine whether CEA is complementary to carbohydrate antigen 19-9 (CA19-9) in prognosis prediction after pancreatic cancer curative resection. We retrospectively reviewed records of 144 stage II curatively resected pancreatic cancer patients with preoperative and postoperative CEA and CA19-9 levels. Patients with normal preoperative CA19-9 were excluded. R0 resection margin, adjuvant treatment, and absence of angiolymphatic invasion were associated with better overall survival. There was no significant difference in median survival according to preoperative CEA levels. However, patients with normal postoperative CA19-9 (59.8 vs.16.2 months, P < 0.001) and CEA (29.4 vs. 9.3 months, P = 0.001) levels had longer overall survival than those with elevated levels. Among 76 patients with high postoperative CA19-9 levels, a better prognosis was observed in those with normal postoperative CEA levels than in those with elevated levels (19.1 vs. 9.3 months, P = 0.004). Postoperative CEA and CA19-9 levels are valuable prognostic markers in resected pancreatic cancer. Normal postoperative CEA levels indicate longer survival, even in patients with elevated postoperative CA19-9.

New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment.

Surgical outcomss and prognostic factors in patents with synchronous colorectaal liver metastases / Resultados do tratamento cirúrgico e de estudo dos fatores prognósticos em pacientes com metástases hepáticas sincrônicas do câncer colorretal

Context Colorectal cancer is the second most prevalent cancer worldwide, and the liver is the most common site of metastases. Surgical resection of colorectal liver metastases provides the sole possibility of cure and the best odds of long-term survival. Objectives To describe surgical outcomes and identify features associated with disease prognosis in patients submitted to synchronous colorectal cancer liver metastasis resection. Methods Retrospective study of 59 patients who underwent surgery for synchronous colorectal cancer liver metastasis. Actuarial survival and disease-free survival were assessed, depending on the prognostic variable of interest. Results Postoperative mortality and morbidity rates were 3.38% and 30.50% respectively. Five-year disease-free survival was estimated at 23.96%, and 5-year overall survival, at 38.45%. Carcinoembryonic antigen levels ≥50 ng/mL and presence of three or more liver metastasis were limiting factors for disease-free survival, but did not affect late survival. No patient with liver metastases and extrahepatic disease had disease-free interval longer than 20 months, but this had no significance or impact on long-term survival. None of the prognostic factors assessed had an impact on late survival, although no patients with more than three liver metastases survived beyond 40 months. Conclusions Although Carcinoembryonic antigen levels and number of metastases are prognostic factors that limit disease-free survival, they had no impact on 5-year survival and, therefore, should not determine exclusion from surgical treatment. Resection is the best treatment option for synchronous colorectal liver metastases, and even for patients with multiple metastases, large tumors and extrahepatic disease, it can provide long-term survival rates over 38%. .

Contexto O câncer colorretal é o segundo câncer mais prevalente no mundo e, o fígado é o principal local das metástases. A ressecção cirúrgica da metástases hepáticas colorretais proporciona a única possibilidade de cura e as melhores chances de sobrevida a longo prazo. Objetivos Avaliar os resultados do tratamento cirúrgico e identificar fatores associados ao prognóstico da doença em pacientes com metástases hepáticas sincrônicas de câncer colorretal submetidos à ressecção. Métodos Estudo retrospectivo de 59 pacientes submetidos à ressecção de metástases hepáticas sincrônicas do câncer colorretal, visando à identificação de fatores relacionados ao prognóstico. Foram estudadas a sobrevida atuarial e sobrevida livre de doença, conforme as variáveis. Resultados A mortalidade e morbidade pós-operatórias foram de 3,38%, e 30,50%, respectivamente. A sobrevida livre de doença estimada em 5 anos foi de 23,96%, e a sobrevida tardia, no mesmo período, foi de 38,45%. O valor do antígeno cárcino-embrionário igual ou superior a 50 ng/mL e o número de metástases maior que três representaram fatores prognósticos limitantes da sobrevida livre de doença, porém sem interferir na sobrevida tardia. Pacientes com metástases hepáticas e doença extra-hepática, submetidos à ressecção, não apresentaram sobrevida livre de doença acima de 20 meses, porém sem significância e sem impacto na sobrevida a longo prazo. Nenhum dos fatores prognósticos estudados interferiu na sobrevida tardia, porém não foi observada sobrevida além de 40 meses em pacientes com mais de três metástases hepáticas. Conclusões Apesar do valor do antígeno ...

Diagnostic values of gene expression of cytokeratin - 19 mrna and mammaglobin mrna in breast cancer patients using real-time polymerase chain reaction

Breast cancer is the most frequent cancer in women. It constitutes almost 20% of all malignancies in women. Currently it affects approximately 6% of the female population. Even before clinical detection of a primary tumour, cancer cells can invade the adjacent structures from where they travel through lymphatic and blood vessels as circulating tumour cells [CTCs]. CTCs colonize distant organ sites as disseminated tumour cells [DTCs] and eventually form microscopic deposits [micrometastasis < 2 mm in diameter], which may remain dormant, but then ultimately lead to an overt metastatic disease. Cytokeratins [CKs] have become the most widely accepted protein markers for the detection of epithelial tumour cells in mesenchymal tissues, BM, blood and lymph nodes. Based on its breast cancer-association and somewhat unique breast-specific pattern of expression, mammaglobin was believed to be an excellent candidate for a novel and clinically useful breast tumor marker, especially in detecting micrometastasis. This study was performed on one hundred female Individuals. They classified into: Group I: 20 apparently healthy females as control group. Group II: 20 females with stage I breast cancer . Group HI: 20 females with stage II breast cancer. Group IV: 20 females with stage III breast cancer. Group V: 20 females with stage IV breast cancer. The following specific investigations were done for all the studied persons:-Cancer Antigen 15-3 [CA15-3] and Carcinoembryonic Antigen [CEA] using chemilmnmescent immunometric assay [IMMULITE 1000 Analyzer]. Cytokeratin-19 mRNA [CK-19] mRNA and mammaglobin mRNA by Real-time polymerase chain reaction [RT-PCR]. In group I [control group]: All the 20 healthy control females had low expression values for CK-19 and Mammaglobin. In group 2 [stage I breast cancer]: 35% of patients had over expression values for CK-19 and 20% had over expression values for Mammaglobin. In group 3[stage II breast cancer]: 47.4% of patients had over expression values for CK-19 and 47.4% had over expression values for Mammaglobin. In group 4 [stage III breast cancer] 68.4% of patients had over expression values for CK-19 and 73.7% had over expression values for Mammaglobin. In group 5 [stage IV breast cancer]: 95% of patients had over expression values for CK-19 and 95% had over expression values for Mammaglobin. Our findings support that all patients with breast cancer should be evaluated by CK-19 and Mammaglobin as a regular laboratory assessment beside the routine tumour markers specially in early stages of breast cancer to detect CTCs at the time of diagnosis

Carcinoembryoni antigen levels in the peripherl and mesenteric venous blood oof patients with rectal carcinoma / Niveis do antigeno carcinoembrionico no sangue venoso periferico e mesenterico em doentes com carcinoma retal

Context The serum carcinoembryonic antigen (CEA) is an important prognostic factor in colorectal cancer, however the rectum presents different routes of venous drainage, stating that the level of CEA in peripheral and mesenteric rectal tumors may be different, depending on the location of the tumor in the rectal segment. Objective The goal of this study was to evaluate the relationship between the peripheral and mesenteric venous levels of CEA and the association between these levels and the tumour location in the rectums of patients successfully operated on for rectal carcinoma. Methods Thirty-two patients who were surgically treated for rectal carcinoma were divided into patients with tumours located in the upper rectum (n = 11) or lower rectum (n = 21). The CEA values were assessed by electrochemiluminescence immunoassay. Serum and mesenteric CEA levels were associated with the tumour anatomopathological characteristics: location, histological type, cellular differentiation grade, depth of invasion into the rectal wall, angiolymphatic invasion, tumour, node, and metastasis staging; and the CEA index (≤1.0 or ≥1.0 ng /mL). Results Analysis of the serum CEA values using clinical and anatomopathological parameters revealed no significant association with tumour location, histological type, cellular differentiation grade, depth of invasion into the intestinal wall, and tumour, node, and metastasis staging. The mesenteric CEA levels were significantly associated with the tumour location (P = 0.01). The CEA values in the mesenteric venous blood and the presence of angiolymphatic invasion (P = 0.047) were significantly different. A significant relationship was found between the CEA index value and the rectal tumour location (P = 0.0001). Conclusions The CEA levels were higher in the mesenteric vein in tumours located in the upper rectum and in the presence of angiolymphatic invasion. CEA drainage from lower rectum adenocarcinomas ...

Contexto O antígeno carcinoembriônico (CEA) sérico é um importante fator de prognóstico do câncer coloretal, contudo o reto apresenta diferentes vias de drenagem venosa, indicando que o nível do CEA periférico e mesentérico nos tumores retais podem ser diferentes, na dependência da localização da neoplasia no segmento retal. Objetivo Avaliar em doentes operados curativamente de carcinoma do reto, a relação entre o nível venoso periférico e portal do CEA e a associação desses níveis com a localização da neoplasia no reto. Método Trinta e dois doentes operados por carcinoma retal foram divididos em pacientes com tumores situados no reto alto (n = 11) e no reto baixo (n = 21). A análise dos valores de CEA foi determinada por imunoensaio de eletroquimioluminescência. As dosagens do CEA sérico e mesentérico foram associadas aos aspectos anatomopatológicos da neoplasia (localização da neoplasia, tipo histológico, grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática); estadiamento tumor, nódulo e metástase e; ao índice do CEA (≤1,0 ou ≥1,0 ng/mL). Resultados A análise dos valores de CEA sérico com os parâmetros clínicos e anatomopatológicos não revelou associação significante com a localização do tumor, tipo histológico, grau de diferenciação celular, nível de profundidade de invasão na parede intestinal e estadiamento tumor, nódulo e metástase. Os valores dos níveis mesentéricos do CEA apresentaram associação significante com a localização do tumor (P = 0,010). Observou-se diferença significante entre os valores do CEA no sangue venoso mesentérico e a presença de invasão ...

[ effects of smoke of waterpipe and immobilization stress on serum level of CEA in female rats]

Studies have indicated that serum level of tumor markers is influenced by several factors. This study was carried out aimed at evaluating the effects of smoke of waterpipe and immobilization stress and on the serum level of CEA in female rats. In this study, 20 female Wistar rats were randomly divided into four groups of 5 each: 1- control group; 2 waterpipe smoke receiving group; 3- under immobilization; 4- waterpipe smoke receiving and immobilized. Waterpipe smoke was given 10 times a day during 10-min periods with 5-min resting time, and chronic immobilization was performed for 2 periods of 2 h daily with 2 h resting time between the periods, and. After 7 weeks, blood samples were collected using cardiac puncture technique, and then, serum level of CEA was measured by radioimmunoassay technique. The data were compared between groups by analysis of variance at p=0.001 significance level. The serum level of CEA significantly increased in waterpipe smoking and also immobilized rats as well as rats under both intervention compared to the control group [p<0.001]. Also, there was a significant difference in serum CEA level between waterpipe smoking and immobilized rats [p<0.001]. On the other hand, there was significant difference in CEA level in rats under both interventions and the two latter groups [p<0.001]. The findings of this study revealed that waterpipe smoking and immobilization stress can cause a sharp increase in the serum level of CEA

Breast cancer proliferative activity: is it the source of serum free DNA?

To study the relationship between serum DNA and breast cancer proliferative activity, then compare the diagnostic and prognostic values of serum DNA, TPS and CEA. A total of 100 breast cancer patients before surgery and 50 apparently healthy controls were analyzed for serum DNA, TPS and CEA. Serum DNA levels were nonsignificantly correlated with serum TPS levels. Serum DNA, TPS and CEA levels were significantly higher in patients than controls. Using ROC curve analysis, serum TPS and DNA had the highest AUC compared to serum CEA. Neither serum TPS, DNA nor CEA correlated with breast cancer clinicopathological data. Only serum CEA was significantly correlated with patients' disease-free survival. Neither Breast cancer mass nor proliferative activity is the source of serum free DNA. Serum TPS is superior to DNA and CEA as a diagnostic marker for breast cancer. Only preoperative serum CEA has a prognostic role in predicting relapse of breast cancer patients, but not serum TPS or DNA

A Comparative Study on Serum Immunoglobulin and Tumor Marker Levels in the Patients with Autoimmune Pancreatitis and Pancreatobiliary Malignancies / 대한소화기학회지

BACKGROUND/AIMS: Autoimmune pancreatitis (AIP) often occurs with obstructive jaundice in old age in cases of weight loss, mimicking pancreatobiliary cancer. This study aimed to determine the sensitivity and specificity serum IgG, IgG4 and CEA, CA 19-9 levels for the diagnosis of AIP and their ability to distinguish AIP from pancreatobiliary cancer. METHODS: The level of serums IgG, IgG4 and CEA, CA 19-9 were measured in 413 patients including 125 with AIP, 201 with pancreatic cancer, and 87 with cholangiocarcinoma. RESULTS: Among AIP patients, 43.2% (54/125) showed elevated IgG levels (> or =1,800 mg/dL) and 52% (65/125) showed elevated IgG4 levels (> or =135 mg/dL). Sensitivity and specificity of elevated serum IgG for diagnosis AIP were 43% and 88% respectively, and 52% and 97%, respectively for elevated serum IgG4. When the cut-off value of serum IgG4 was raised to 270 mg/dL (twice the upper limit of normal), the specificity improved to 100%. About 25% of the AIP patients showed an increased level of CA 19-9 at >37 U/mL and about 12.2% of them showed an increased level of CA 19-9 at >100 U/mL. On the contrary, only 1.8% of the AIP patients showed an increased level of CEA at >6.0 ng/mL. CONCLUSIONS: To avoid unnecessary surgeries resulting from a misdiagnosed pancreatobiliary cancer as opposed to AIP, it is necessary to consider both serum immunoglobulin and tumor marker. In particular, because high level of IgG4 (> or =270 mg/dL) and CA19-9 (>100 U/mL) are relatively rare in pancreatobiliary cancer and AIP, respectively, they will be helpful in differential diagnosis.

Serum CA 19-9 and CEA Levels as a Prognostic Factor in Pancreatic Adenocarcinoma

PURPOSE: To investigate the use of pretreatment carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) as prognostic factors to determine survival in pancreatic adenocarcinoma. MATERIALS AND METHODS: A retrospective review of the medical records of patients who were diagnosed with pancreatic adenocarcinoma and received surgery, chemoradiotherapy or chemotherapy was performed. Factors, including CA 19-9 and CEA, associated with the survival of pancreatic cancer patients were analyzed. RESULTS: Patients with the median age of 65 years were included (n=187). Elevated serum CA 19-9 levels and CEA levels were observed in 75.4% and 39% of patients at diagnosis, respectively. CEA was correlated with tumor stages (p=0.005), but CA 19-9 was not. CA 19-9 and CEA were elevated in 69.0% and 33.3% of patients with resectable pancreatic cancer, and elevated in 72.9% and 47.2% of patients with advanced pancreatic cancer, respectively. The median overall survival of the normal serum CEA group was longer than that of the elevated serum CEA group (16.3 months vs. 10.2 months, p=0.004). However, the median overall survival of the normal serum CA 19-9 group was not different from that of the elevated serum CA 19-9 group (12.4 months vs. 13.5 months, p=0.969). The independent factors associated with overall survival were advanced pancreatic cancer [harzard ratio (HR) 4.33, p=0.001] and elevated serum CEA level (HR 1.52, p=0.032). CONCLUSION: Patients with elevated serum CEA level at diagnosis demonstrated poor overall survival. Pretreatment CEA level may predict the prognosis of patients with pancreatic adenocarcinoma.

Usefulness of Carcinoembryonic Antigen for Monitoring Tumor Progression during Palliative Chemotherapy in Metastatic Colorectal Cancer

PURPOSE: To evaluate the efficacy of carcinoembryonic antigen (CEA) measurement for monitoring tumor progression during palliative chemotherapy in metastatic colorectal cancer. MATERIALS AND METHODS: Forty-eight patients with initially unresectable metastatic colorectal cancer (n=26, 54.2%) or recurrent unresectable metastatic colorectal cancer (n=22, 45.8%) received FOLFOX-4 chemotherapy for palliation. Serum CEA levels and carbohydrate antigen 19-9 levels were measured and computed tomography (CT) studies were performed prior to chemotherapy and after 3 cycles of chemotherapy. From the CT images, tumor responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria and categorized as complete response, partial response, stable disease, and progressive disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tumor marker assessments for determining tumor response were calculated. RESULTS: The sensitivity, specificity and diagnostic accuracy of CEA assessment for prediction of disease progression were 50%, 77% and 69%, respectively. When the patients were dichotomized according to baseline CEA level, the initially elevated CEA group showed higher sensitivity and higher diagnostic accuracy compared to the initially normal CEA group (sensitivity=67% vs. 20%; diagnostic accuracy=71% vs. 62%). CONCLUSION: CEA assessment could be useful for monitoring tumor progression during palliative chemotherapy in only patients with initially elevated CEA level.

Podoplanin, alpha-Smooth Muscle Actin or S100A4 Expressing Cancer-Associated Fibroblasts Are Associated with Different Prognosis in Colorectal Cancers

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases. PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/alpha-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/alpha-SMA(high) or PDPN-/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.

Impact of Interleukin-10 Gene Polymorphisms on Survival in Patients with Colorectal Cancer

Chronic inflammation is thought to be the leading cause of colorectal cancer, and interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine that regulates inflammatory responses in the gastrointestinal tract. Although several single nucleotide polymorphisms (SNPs) in IL10 have been associated with the risk of colorectal cancer, their prognostic significance has not been determined. Two hundred and eighty-two colorectal cancer patients were genotyped for two candidate cancer-associated SNPs in IL10. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of death compared with the TT+TG genotypes (P=0.011). The patients with IL10 rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis (log-rank P=0.007) and in multivariate Cox regression model (P=0.044) adjusting for age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, and perineural invasion. In conclusion, our results suggest that IL10 rs3021094 might be a valuable prognostic biomarker for colorectal cancer patients.

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.

Serial tumour markers serum carcinoembryonic antigen and cancer antigen 15-3 assays in detecting symptomatic metastasis in breast cancer patients

The value of serum tumour markers in the prognosis of patients with breast cancer is controversial. This prospective study in Yazd, Islamic Republic of Iran, assessed the value of the tumour markers carcinoembryonic antigen [CEA] and cancer antigen [CA] 15-3 in 159 patients with primary breast cancer. CEA and CA15-3 assays [mean 14 per patient] were performed at diagnosis, end of surgery and chemotherapy and every 3 months in the first 2 years and every 6 months in second 2 years of the follow-up period. During follow-up, 33 patients [20.8%] presented symptomatic metastasis. A significant relationship was seen between metastasis status and positive CEA and CA15-3 levels. The sensitivity and specificity were 66.7% and 98.4% for CEA respectively and 84.8% and 91.3% for CA15-3 respectively. Optimum cut-offs were 4.95 ng/mL and 30.5 U/mL for CEA and CA15-3 respectively