Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer.

We studied the specificity and sensitivity of progastrin releasing peptide (ProGRP) in 37 healthy subjects and 195 patients with benign and 149 with malignant diseases other than lung cancer. Likewise, we compared the ProGRP with other tumor markers used in lung cancer (CEA, SCC, CYFRA and NSE) in 187 patients with NSCLC and in 66 SCLC patients. We considered 50 pg/ml, 5 ng/ml, 2 ng/ml, 3.3 ng/ml and 20 ng/ml as the upper limits of normality for ProGRP, CEA, SCC, CYFRA 21-1 and NSE, respectively. Abnormal ProGRP serum levels were found in 10% of patients with benign diseases and in 13% of patients with malignancies other than lung. Renal failure was the main source of false-positive results (51.6%). Slightly raised ProGRP serum levels, excluding renal failure, were found in 4.1% of patients with benign diseases (<80 pg/ml) and in 5% of patients with malignancies other than lung cancer or neuroendocrine tumors (<120 pg/ml). Abnormal levels of ProGRP, NSE, CEA, CYFRA and SCC were found in 30%, 22.5%, 55.6%, 65.2% and 26.7% of NSCLC and in 73%, 64%, 53%, 46% and 4.5% of SCLC, respectively. Tumor marker serum levels were related to histological type and tumor extension, with ProGRP being the most sensitive marker in SCLC, CEA in adenocarcinomas and CYFRA 21-1 in squamous tumors. The most sensitive combinations of tumor markers were ProGRP and NSE in SCLC (88%), and CEA plus CYFRA in NSCLC (82%). In summary, ProGRP is the tumor marker of choice in SCLC and NSE is a complementary tumor marker in this histological type.

Hypophosphatemic osteomalacia: a report of five cases and evaluation of bone markers.

In this study, we analyzed the changes in biochemical markers of bone turnover in five patients with hypophosphatemic osteomalacia. The following bone markers were evaluated: among bone formation markers, total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), osteocalcin (bone Gla protein, BGP) and procollagen type I N propeptide (PINP); among bone resorption markers, serum beta C-terminal cross-linked telopeptide of type I collagen (s-CTx), urinary hydroxyproline (HYP), and N-terminal and alpha and beta C-terminal cross-linked telopeptides of collagen (NTx and alpha- and beta-CTx). In addition, the alpha/beta-CTx ratio was evaluated. TAP and BAP were the markers with the highest increase in both frequency and magnitude. Conversely, BGP values were low in all patients. Collagen-related markers were slightly increased in nearly half of the patients. Among them, PINP showed the highest proportion of increased values. The alpha/beta-CTx ratio was within normal values in all patients. In conclusion, TAP and BAP seem to be the best bone markers in the diagnostic evaluation of hypophosphatemic osteomalacia. In addition, their high values associated with low levels of BGP provide an even more reliable biochemical profile of this disorder, when associated with the classic mineral and skeletal homeostasis abnormalities.

Comparison of several combinations of free, complexed, and total PSA in the diagnosis of prostate cancer in patients with urologic symptoms.

OBJECTIVES: To compare the diagnostic efficacy of prostate-specific antigen (PSA) and the PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between prostate cancer and benign prostatic hyperplasia. METHODS: We measured the serum levels of total PSA (tPSA; Hybritech and Bayer), fPSA (Hybritech), and cPSA (Bayer) in 72 patients with prostate cancer and 128 patients with benign prostatic hyperplasia. RESULTS: Receiver operating characteristic curves were used for comparison of these tests. The greatest area under the curve was observed for the fPSA/cPSA ratio and the fPSA/tPSA ratio (0.757 and 0.754, respectively). The substitution of the fPSA/tPSA ratio with the fPSA/cPSA ratio in the diagnostic scheme of prostate cancer improved the diagnostic accuracy, with similar sensitivity and an increment in specificity (41% versus 45%). CONCLUSIONS: The fPSA/cPSA ratio ensures a reduction in negative biopsies in the PSA gray zone. We suggest substituting the fPSA/tPSA ratio with the fPSA/cPSA ratio for patients with a PSA level between 4 and 10 ng/mL.

Pro-gastrin-releasing peptide in patients with benign and malignant diseases.

The specificity and sensitivity of pro-gastrin-releasing peptide (ProGRP) was evaluated in 37 healthy subjects, 197 patients with benign diseases and 310 patients with malignant diseases of different origins. Abnormal ProGRP serum levels (>50 pg/ml) were found in 10% of the patients with benign diseases and in 26.1% of the patients with active cancer. None of the healthy subjects had abnormal ProGRP levels. The benign disease with the highest ProGRP concentration was renal failure, with abnormal values in 51.6% of the patients studied. Excluding patients with renal failure or patients with creatinine levels greater than 1.5 mg/dl, raised ProGRP values (<80 ng/ml) were found in 2.5% (4/160) of patients with benign diseases and in 4.9% of patients with active malignancies other than lung cancer or neuroendocrine tumors (<110 ng/ml). Abnormal ProGRP serum levels were found in 26.2% of patients with non-small cell lung cancer (NSCLC) (mean 40.5 +/- 35.4 pg/ml) and in 76.8% of patients with small cell lung cancer (SCLC) (mean 694 +/- 1,776 pg/ml) (p < 0.001). ProGRP serum levels >300 pg/ml were only found in SCLC patients (41.4%). ProGRP results were related to tumor extension in SCLC (sensitivity in limited disease 58.3%, in extensive disease 95.5%) but not in NSCLC. In summary, renal failure is the most frequent source of false-positive results with ProGRP, and this marker is useful in the histological differential diagnosis of lung cancer.

[Usefulness of PSA and its fractions in the diagnosis of prostate cancer]. / Antígeno prostático específico y sus fracciones en el diagnóstico del cáncer de próstata.

BACKGROUND AND OBJECTIVE: The description of different forms of PSA has opened a new strategy in the diagnosis of prostate cancer. The measurement of the ratio between free PSA and PSA in the group of patients with a PSA level between 4 and 10 ng/ml decreases the number of negative biopsies. The aim of our study was to compare the diagnostic efficacy of PSA and PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between Pca and benign prostate hyperplasia (BPH). PATIENTS AND METHOD: We measured the serum levels of PSA, free PSA and cPSA in 56 patients with Pca and 94 patients with BPH. RESULTS: ROC curves were used for the comparison of tests. The biggest area under the curve (AUC) was observed for the ratios fPSA/cPSA and fPSA/PSA (0.718 and 0.712, respectively). When we compared the AUC between PSA and cPSA, then AUC for cPSA was higher than AUC for PSA (0.602 and 0.567, respectively). We observed similar results in the group of patients with PSA levels between 4 and 10 ng/ml. CONCLUSIONS: The diagnostic accuracy of cPSA is higher than that of PSA. Moreover, in the differential diagnosis between prostate cancer and BPH, the use of PSA ratios (fPSA/cPSA or fPSA/PSA) increases the diagnostic accuracy obtained with the measurement of PSA or cPSA.

Antígeno prostático específico y sus fracciones en el diagnóstico del cáncer de próstata / Usefulness of PSA and its fractions in the diagnosis of prostate cancer

FUNDAMENTO Y OBJETIVO: La descripción de distintas formas circulantes de antígeno prostático específico (PSA) ha abierto una nueva estrategia en el diagnóstico del cáncer de próstata. La determinación del índice entre PSA libre y PSA total en el grupo de pacientes con valores de éste último entre 4 y 10 ng/ml ha disminuido el número de biopsias negativas. El objetivo de nuestro estudio ha sido comparar la eficacia diagnóstica del PSA y sus fracciones (PSA libre y PSA ligado a las proteínas inhibidoras de las proteasas o PSAc) en el diagnóstico diferencial entre cáncer de próstata e hiperplasia benigna de próstata. PACIENTES Y MÉTODO: Hemos dosificado la concentración de PSA total, PSA libre y PSAc en 56 pacientes con cáncer de próstata y 94 pacientes con hiperplasia benigna de próstata. RESULTADOS: Se han empleado curvas ROC para realizar la comparación de estos tests. Las mayores áreas bajo la curva se obtuvieron para los índices entre PSA libre y PSAc y entre PSA libre y PSA total (0,718 y 0,712, respectivamente). El área bajo la curva del PSAc fue mayor que la del PSA total (0,602 y 0,567, respectivamente). Los resultados hallados en el subgrupo de pacientes con valores de PSA total entre 4 y 10 ng/ml fueron semejantes a los del grupo total. CONCLUSIONES: La eficacia diagnóstica del PSAc es mayor que la del PSA total. En el diagnóstico diferencial entre cáncer de próstata e hiperplasia benigna de próstata el uso de los índices de PSA aumenta la eficacia diagnóstica obtenida con la dosificación de PSA total o PSAc (AU)

Complexed prostate-specific antigen for the detection of prostate cancer.

BACKGROUND: The description of a new method for the measurement of complexed prostate-specific antigen (cPSA) offers a new approach to the diagnosis of prostate cancer. PATIENTS AND METHODS: We measured PSA (Hybritech and Bayer), free PSA (Hybritech) and complexed PSA (Bayer) in 72 patients with prostate cancer and 128 with benign prostate hyperplasia. RESULTS AND CONCLUSION: We found an increase of sensitivity using 25 and 7 ng/mL as cut-offs for cPSA in relation to total PSA using as cut-offs 4 and 10 ng/mL (96 and 36% vs. 92 and 35.5%). Similar differences were found for specificity (78% and 31% for cPSA vs. 73% and 29% for total PSA). Therefore, we defined a gray zone for patients with cPSA between 2.5 and 7 ng/mL for which the measurement of the free/complexed PSA ratio saves an important number of negative biopsies maintaining a higher sensitivity.

Effect of surgical menopause and Paget's disease of bone on the isomerization of type I collagen carboxyterminal telopeptide: evolution after antiresorptive therapy.

The objective of this study was to analyze the effect of surgical menopause and Paget's disease of bone, as well as the influence of therapy, on the isomerization of the carboxyterminal telopeptide of type I collagen (CTX). Fourteen women who had undergone surgical menopause and had begun hormone replacement therapy (HRT) after surgery were recruited. Results for these women were compared with those of 29 patients with Paget's disease of bone treated with tiludronate (400 mg/day) for 3 months, and with those of a group of 21 healthy premenopausal women (control group I). In addition, 14 healthy individuals with an age range similar to that of the pagetic patients (control group II) were included in the study. Urine samples were analyzed for levels of nonisomerized and beta-isomerized CTX (alpha-CTX and beta-CTX). Biochemical determinations were performed 3 months after surgical menopause and after 3 and 9 months of HRT, and at baseline, and 1 and 6 months after tiludronate treatment in the pagetic patients. The average levels of alpha-CTX and beta-CTX were higher in patients than in controls. In patients after surgical menopause, because of their greater increase of beta-CTX, the alpha-CTX/beta-CTX ratio was lower than that of control group I (0.881 +/- 0.3 vs 1.515 +/- 0.8; P < 0.05). In contrast, at baseline, pagetic patients showed marked increases in alpha-CTX levels, resulting in a higher alpha-CTX/beta-CTX ratio than that of control group II (2.879 +/- 1.3 vs 0.96 +/- 0.25; P < 0.0001). The average percent decrease in both markers after therapy was similar in both conditions (-60% for alpha-CTX and -44% for beta-CTX after 3 months of HRT in the surgical menopause group, vs -66% for alpha-CTX and -41% for beta-CTX in the pagetic group, 1 month after finishing tiludronate therapy; P, NS), resulting in a significant decrease of the alpha-CTX/beta-CTX ratio in pagetic patients (2.879 +/- 1.3 vs. 1.614 +/- 0.8; P < 0.001). In conclusion, surgical menopause is associated with a decrease in the urinary alpha-CTX/beta-CTX ratio because of the higher increase in the beta-CTX level after menopause. Pagetic patients show an increase in this ratio, compared with the control value, and the ratio decreases after bisphosphonate treatment. The response to therapy was similar in both conditions, with a comparable decrease of both markers. These findings show how bone markers may contribute to the understanding of pathophysiologic mechanisms in bone diseases.

El laboratorio Clínico: un área en constante evolución / The Clinical Laboratory: An Area in Constant Evolution

No disponible

Serum levels of beta2-microglobulin, neopterin, TNF-alpha and soluble receptors of TNF-alpha and interleukin-2 in intravenous drug abusers according to HIV-1 status and stage of the HIV-1 infection.

OBJECTIVE: To compare the serum levels of beta2-microglobulin (beta2M), neopterin (NP), TNF-alpha and soluble receptors of TNF-alpha (sTNF-R55 and sTNF-R75) and interleukin-2 (sIL-2R) in a population of intravenous drug abusers according to whether or not they had HIV-1 infection and to the stage of the HIV-1 infection. METHODS: A cross-sectional study was performed at four drug detoxification centers in Barcelona, and the HIV outpatient clinic at Hospital Clínic in Barcelona. Three cohorts of intravenous drug abusers (IVDAs)-105 HIV-1-uninfected patients (cohort A), 174 with asymptomatic HIV-1 infection (cohort B) and 39 with AIDS (cohort C)-were enrolled. On the first visit, the following laboratory tests were performed: hemogram and platelet count, hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies, B2M, NP, sIL-2R, TNF-alpha, and TNF receptors (sTNF-R55 and sTNF-R75). RESULTS: The three cohorts were homogeneous according to sex, type of drug, average number of intravenous doses of drug in 1 day, and hepatitis B infection. Patients with AIDS were older than those of cohort A and B (p<0.0001). HIV-negative IVDAs were co-infected with hepatitis C virus less frequently than were HIV-positive IVDAs (80% versus 91%, p<0.03). Among HIV-1-negative IVDAs (cohort A), almost all (from 86% to 95%, depending on the marker) individual values were within the normal boundaries of our laboratory. With a single exception (level of sTNF-R55 in cohort B compared with cohort A, p=0.15), levels of all markers were significantly higher in asymptomatic HIV-1-infected (cohort B) when compared with uninfected patients (cohort A), and in AIDS patients (cohort C) when compared with both cohorts A and B. There was a significant positive correlation between levels of ss2M and NP (r=0.56; p<0.01), ss2M and TNF (r=0.65, p<0.01) and NP and TNF (r=0.76, p<0.01). There was no correlation between levels of sIL-2R and levels of ss2M, NP or TNF and its receptors. CONCLUSIONS: Intravenous drug abuse does not modify serum levels of ss2M, NP, sIL-2R, TNF-alpha, and TNF receptors (sTNF-R55 and sTNF-R75). Levels of these markers increase significantly when an HIV-1 infection occurs and when there is progression to AIDS.