Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma

ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.

PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35?

PURPOSE: To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIALS AND METHODS: From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20%, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS: All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1%): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50%, 90.6 vs 71.9%, 27.9 vs 41.8%, 31.9 vs 31.5% and 88.9 vs 80%, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS: Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1% of biopsies while missing 9.4% and 28% diagnosis of PCa.

Correlation between the preoperative serum prostate specific antigen, Gleason score, and clinical staging with pathological outcome following robot-assisted radical prostatectomy: An Indian experience.

Objectives: To correlate the preoperative serum prostate specific antigen (PSA), Gleason score, and clinical staging with pathological outcome following robot-assisted radical prostatectomy (RARP) in Indian men with clinically localized cancer prostate. Materials and Methods: A prospective study analysis was done for 166 consecutive patients of prostate cancer who underwent RARP at our center from June 2006 to October 2009. Preoperative workup included serum PSA, biopsy Gleason score, and clinical staging. The preoperative parameters were correlated with final Gleason score, capsular penetration, seminal vesicle involvement, and lymph node status on final histopathology. Results: The mean age was 64 years (range: 50-76 years) with mean and median PSA of 17.98 ng/ml (range: 0.3-68.3 ng/ml) and 12.1 ng/ml, respectively. With increase in preoperative Gleason score, chance of organ confinement decreases (P=0.002) and capsular penetration increases (P=0.004) linearly. With increasing serum PSA, there is linear decrease in trend of organ-confined disease (P=0.03) and increased chances of seminal vesicle involvement (P=0.02). Patients with higher clinical stage have less probability of localized disease (P=0.007) and more chances of capsular penetration (P=0.04) and seminal vesicle involvement (P=0.004). Conclusion: Our data suggest that patients with higher preoperative serum PSA, Gleason score, and clinical stage have more chances of advanced pathological stage following RARP.

Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. In Egypt, HCC was reported to account for about 4.7% of chronic liver disease (CLD) patients. Squamous cell carcinoma antigen (SCCA) has been reported to be strongly expressed in HCC tissue hampering its extensive use in clinical practice. AIM: To evaluate the clinical usefulness of serum SCCA levels as a serological marker for early detection of HCC among high-risk patients compared to AFP. MATERIALS AND METHODS: The study comprised of three groups. Group A included 30 patients with CLD diagnosed based on clinical, laboratory, and ultrasonographical investigations; group B included 49 patients with HCC diagnostically confirmed by spiral CT, elevated alfafetoprotein (AFP), and/or liver biopsy; and group C, the control group, included 15 healthy subjects matched for age and sex. All groups were subjected to thorough history taking, full clinical examination, and laboratory investigations including liver functions, viral markers, and AFP and SCCA estimation using ELISA technique. RESULTS: This study revealed a highly significant difference between patients with HCC, CLD, and controls regarding serum SCCA levels (5.138 +/- 7.689, 1.133 +/- 0.516, and 0.787 +/- 0.432 ng/ml, respectively). SCCA level was persistently elevated in patients with HCC with normal AFP levels representing its useful role in early detection and follow-up of patients treated for HCC. The area under the curve (AUC) of SCCA was 0.869 (95% CI 0.783-0.929), the cut-off value was established at 1.5 ng/ml with sensitivity of 77.6% and specificity of 84.4%). The difference between AUC of SCCA and that of AFP was 0.09 which mounted statistical significance. CONCLUSIONS: SCCA could represent a useful tool as a marker for detection of HCC.

Cystic fibrosis and neonatal screening / Fibrose cística e a triagem neonatal

The clinical and diagnostic aspects of cystic fibrosis have been extensively reviewed, with an emphasis on neonatal screening. This systematic literature review involved a search for relevant contributions in the PubMed and SciELO databases. The first references to cystic fibrosis date to the Middle Ages. Cystic fibrosis is the most frequent autosomal recessive hereditary disease among Caucasians (1:2,000 to 3,500). More than 1,000 mutations lead to the disease, the most common being "F508, with 70 percent prevalence among Canadian, Northern European, and American Caucasians and 23 to 55 percent prevalence among Brazilians. The basic defect is in chloride ion secretion. Cystic fibrosis screening has long been controversial, and after almost three decades, there are few nationwide programs (most are regional or local). However, the U.S. Centers for Disease Control and Prevention (CDC) has concluded that screening for cystic fibrosis is justified. The lack of a specific screening test and the ethnic heterogeneity of the Brazilian population pose challenges for neonatal screening.

Aspectos clínicos e diagnósticos da fibrose cística são revistos de modo abrangente, com ênfase na triagem neonatal. Esta revisão sistematizada da literatura envolveu busca de contribuições relevantes nos bancos de dados PubMed e SciELO. Referências sobre fibrose cística existem desde a Idade Média. É a doença hereditária autossômica recessiva mais freqüente em caucasianos (1:2.000 a 3.500). Mais de mil mutações levam à doença, a mais comum: "F508 (prevalência: 70 por cento em caucasianos canadenses, americanos e norte-europeus; de 23 a 55 por cento em brasileiros). O defeito básico ocorre na secreção do íon cloro. Sua triagem é assunto polêmico e apesar de estar disponível há quase três décadas, por meio de diferentes protocolos, poucos programas de abrangência nacional existem. Entretanto, o Centers for Disease Control and Prevention, dos Estados Unidos, afirma que o rastreamento neonatal para fibrose cística é justificado. A falta de um teste específico e a heterogeneidade étnica da população brasileira dificultam sua triagem neonatal.

Pesquisa de células malignas circulantes em pacientes com melanoma maligno de coróide / Detection of circulating malignant cells in patients with uveal melanoma

OBJETIVO: Avaliar a possibilidade de identificação de células malignas circulantes nas amostras de sangue periférico de pacientes brasileiros com melanoma maligno de coróide enviadas para análise no exterior. MÉTODOS: Os marcadores melan-A e tirosinase foram usados para detectar a presença de células malignas circulantes, pela transcrição reversa seguida de reação em cadeia da polimerase e análise seqüencial de DNA (RT-nested-PCR), em seis pacientes com melanoma maligno de coróide, diagnosticados no Brasil. RESULTADOS: Cinco pacientes deste grupo (83,33 por cento) foram considerados positivos. A reação de RT-nested-PCR foi positiva para melan-A em quatro (66,7 por cento) e positiva para tirosinase em quatro (66,7 por cento) dos seis pacientes testados. Três (50 por cento) pacientes foram positivos para os dois marcadores. Um (16,7 por cento) paciente foi negativo para ambos marcadores. CONCLUSÃO: A pesquisa de células malignas circulantes usando RT-nested-PCR, foi positiva na maioria dos pacientes estudados. A qualidade das amostras de sangue periférico dos pacientes brasileiros foi mantida no material preservado mesmo após ter sido enviado ao exterior.

PURPOSE: The purpose of our study was to detect circulating malignant cells (CMCs) in oversea-shipped blood samples of patients with uveal melanoma diagnosed in Brazil. METHODOS: Melan-A and tyrosinase were the two markers used for the detection of CMCs, using reverse transcriptase nested polymerase chain reaction (RT-nested-PCR) in 6 patients with uveal melanoma. The expression of beta-actin and GAPDH were used to assess the quality of the material. RESULTS: Five patients (83.33 percent) tested positive for the presence of CMCs. The RT-nested-PCR was positive for melan-A in 4 patients (66.7 percent) and positive for tyrosinase in 4 (66.7 percent) of the 6 patients. Three (50 percent) patients were positive for both markers. One (16.7 percent) patient was negative for both markers. All negative controls were negative. CONCLUSION: The quality of the blood samples shipped overseas, from patients with uveal melanoma, was preserved. The detection of CMCs using RT-nested-PCR was positive in the majority of the patients.

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.

diagnostic value of serum and bile cyfra 21-1, CEA and CA 19-9 in cases of cholangiocarcinoma

The aim of the present study was to assess the diagnostic value of Cyfra 21-1, CA 19-9 and CEA in serum and bile of patients with CCA. The present study was conducted on 20 patients with cholangiocarcinoma [CCA group] diagnosed on clinical and pathological grounds, in addition to 20 cases with benign cholestatic disorder and 20 matched healthy subjects as a control group. Cyfra 2 1-1, CEA and CA 19-9 were measured in serum and bile of patients and in serum of controls. Serum CEA, CA 19-9 and Cyfra 21-1 concentrations were significantly higher in patients with cholangiocarcinoma than patients with benign cholestatic disorder and controls. Moreover, the mean bile .concentrations of CEA, CA 19-9 and Cyfra 21-1 were significantly higher than serum concentrations. The sensitivity, specificity and diagnostic accuracy of serum and bile Cyfra 21-1 were significantly higher than those obtained using either CEA or CA 19-9. The serum and bile concentrations of CEA, CA 19-9 and Cyfra 21-1 were significantly higher in late stages of CCA in comparison to early stages. The addition of tumor markers CEA, CA l9-9 and Cyfra 21-1 to brush cytology increases its sensitivity in diagnosis of cholangiocarcinoma from 44% up to 84%. CEA, CA 19-9 and Cyfra 21-1 measurements in bile are important for the supplementary diagnosis of cholangiocarcinoma. Cyfra 21-1 is a superior tumor marker than CEA in diagnosis cholangiocarcinoma. Combining brush cytology with CEA, CA 19-9 and Cyfra 21-1 can raise the diagnostic yield

Non isotopic assays for tumor markers as a monitor for treatment

Tumor markers [cancer embryonic antigen [CEA], alpha fetoprotein [AFP] and cancer antigens 50, 125 [CA 50 and CA 125] serum levels] were measured by time resolved fluoro and enzyme immunoassays [TRFIA and EIA] in 40 cases of carcinoma of the ovary and uterus. While, rechecking the precision of the non isotopic methods, the coefficient of variation [CV] ranged from 7.7 to 9.4% for CEA and 7.8 to 11.4% for CA 125. Analytical recovery was 97.8% and 95.6%, sensitivity was 0.2 ng/ml and 3 u/ml and the correlation coefficient [r] with RIA was 0.96 and 0.94, respectively. The assays were repeated three months after treatment. A statically significant rise was found in the levels of CEA, AFP and CA 125 before treatment as compared with a control group. A significant drop in the levels occurred in serum CEA, AFP and CA 50 levels in cases of ovarian malignancy and in serum CA 125 in cases of ovarian and uterine malignancy after the three months treatment

Establishment of OVS1 and OVS2 monoclonal antibodies recognizing human ovarian mucinous cystadenocarcinoma.

Two newly established murine monoclonal antibodies (MAbs), OVS1 and OVS2, to human ovarian mucinous cystadenocarcinoma were further characterized for diagnostic efficacy. The specific SA-1 antigen, purified from the tumor extract was identified as a glycoprotein of 29 kDa. A double determinant biotinstreptavidin alkaline phosphatase immunoassay system, containing OVS1 and OVS2 MAbs was used to determine the SA-1 levels in serum. The OVS1 MAb was used as a first antibody because of its high specificity of 96% while OVS2 MAb, with a lower specificity of 8% but greater sensitivity of 78%, was chosen as a second antibody. Matched sera of 64 healthy controls and 90 patients with definite diagnoses of 25 benign diseases, 14 nonovarian cancer and 51 ovarian cancer, were simultaneously measured together with CA 125 values. At cut-off levels of 220 and 360 units/ml, the SA-1 test showed 63% and 43% positive rates respectively in all types of ovarian cancer, compared to 65% and 57% positive rates for CA 125 at cut-off levels of 35 and 60 units/ml, respectively. Sensitivity for SA-1 at 220 units/ml cut-off level in mucinous ovarian cancer was 75% and increased significantly to 85% when the test was combined with CA 125 at 35 units/ml cut-off level. Furthermore, The combination of both tests significantly increased the positive rates to 86% in all types of early stage ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnóstico del cáncer de próstata mediante ecografía transrectal y antígeno prostático específico / Prostatic cancer: PS antigen and transrectal ultrasound

Se estudia un grupo de 64 pacientes con sospecha de cáncer de próstata, mediante ecografía prostática transrectal (EPT), biopsia prostática transrectal y dosaje sérico de antígeno prostático específico (APE). La combinación de hallazgo ecográfico de nódulo hipoecoico con elevación del APE (>=10ng/ml) aportó los mejores resultados diagnósticos para cáncer de próstata: sensibilidad, 78,9 por ciento, especificidad, 75 por ciento y valor predictivo positivo del 88,2 por ciento

Valor del Gleason preoperatorio y del antígeno prostático específico como factores predictivos de metástasis ganglionares en el cáncer de próstata / Value of preoperatory Gleason and of the prostatic specific antigen with predictive factors of lymph node metastases in prostate cancer

Se ha demostrado el significado pronóstico que tiene el volumen tumoral, la invasión de vesículas seminales, compromiso del tejido periprostático y el compromiso de los ganglios linfáticos regionales en el pronóstico del cáncer de próstata, sin embargo el único método realmente confiable para conocer el estado de los mismos continua siendo el análisis anátomo patológico. El objetivo de este trabajo es buscar si existe alguna correlación entre el grado de diseminación tumoral (compromiso ganglionar) y algunas variables de las que se dispone en el preoperatorio como el valor del APE y el Gleason de la biopsia preoperaoria. Para ello se analizó en forma retrospectiva los resultados de 147 pacientes que fueron sometidos a Prostatectomía radical en un período de 9 años. El análisis de los resultados mostró que no existe un valor predictivo en el valor del Gleason preoperatorio conla presencia de ganglios linfáticos comprometidos (p = 0.06), el valor del APE promedio preoperatorio si presentó una correlación positiva con la presencia de metástasis ganglionares (p = 0.006), aunque existe una gran desviación standart en los valores registrados. Utilizando estos valores pudimos construir un modelo de regresión logística, por medio de la cual calcular la probabilidad de tener compromiso linfático conociendo el valor del APE preoperatorio con un valor concordante del 75 por ciento

Evaluación del antígeno prostático específico post tacto rectal: experiencia en 36 pacientes / Evaliuation of specific prostatic antigen after rectal examination: experience in 36 patients

Levels of prostatic epecific antigen may modified with procedures over the prostatic gland. We measured this antigen in 36 hospitalized patients before and inmediately after a digital rectal examination. Antigen levels were 8.3 ñ 21.3 ng/ml before and 13.8 ñ 27.5 ng/ml after the examination (NS). It is concluded that digital rectal examination did not modify antigen levels in our sample

A sequential study of humoral factors in ovarian neoplasms.

A sequential study of serum immunoglobulins, circulating immune-complexes (CIC) and blocking effect of patients' sera on normal T lymphocytes was conducted in 15 patients with benign ovarian tumour, 32 with carcinoma ovary and 20 agematched healthy women. In patients with benign ovarian tumour there was a significant increase in IgG and IgM, while IgA was not altered. In carcinoma, there was no significant change in IgG and IgM but IgA was found to be increased significantly as compared to benign ovarian tumour. Post-operatively, IgM showed a significant increase on the 10th day, probably due to the effect of surgery. There was no significant difference in CIC levels and percentage T cell depression between patients with benign ovarian tumours and healthy controls. In carcinoma ovary both these parameters were increased significantly as compared to benign ovarian tumours. After tumour ablation, they were decreased significantly, until there was recurrence. The alterations in these parameters was not related to any specific histologic type of neoplasm. The study of serum immunoglobulins indicates tumour load, while the estimation of CIC and blocking effect of cancer sera on normal lymphocytes is of a definite diagnostic and prognostic significance.

Identification of tumor markers for cholangiocarcinoma and evaluation of their diagnostic potential.

Results obtained from studies using experimental animal model clearly showed that (1) A marker(s) for CCA does exist; 2) This marker is a glycoprotein with a molecular weight of 200 kDa; (3) It is produced and secreted in vitro by tumor cell lines; (4) It is highly immunogenic in mice and the MAb specific for this antigen is directed against the carbohydrate moiety; (5) This tumor antigen can be detected in serum and bile of tumor-bearing animals by a sandwich ELISA employing this MAb; (6) Kinetic studies show a gradual elevation of this antigen during tumor development; and (7) The elevation of this antigen can be detected at a time when no pathological changes have yet taken place, as judged by microscopic examination. Preliminary work from the human counterpart using human cholangiocarcinoma cell line showed promising results. CCA-specific antigen could be similarly identified and the MAbs produced were highly specific for this 160 kDa antigen.

Study of foetal antigen in haematological malignancy.

Forty patients with different varieties of leukaemia and lymphoma were studied before and after therapy. Red cells and lymphocytes from each patient were tested for foetal antigen by lectin-agglutination test. The antigen was detectable on red cells in all untreated cases, the highest titre being found in chronic myeloid leukaemia. The titre showed significant reduction after treatment in all cases. We conclude that foetal antigen on red cells is a useful diagnostic aid in haematological malignancy and is a good indicator of the outcome of therapy.