Background: Chronic cardiac dysfunction may develop after administration of aggressive chemotherapy, sometimes leading to development of congestive heart failure (CHF). Recently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was implicated as a marker of CHF. In this study we evaluated the predictive role of NTproBNP in patients treated with high-dose chemotherapy (HDC). Methods: NT-proBNP was measured after 62 chemotherapy treatments in 52 patients affected by aggressive malignancies. Blood samples were drawn before the start of HDC, at the end of HDC administration, and 12, 24, 36, and 72 h thereafter. In these patients, echocardiograms were performed regularly during a 1-year followup. Results: Seventeen patients (33%) had persistently increased NT-proBNP, 19 patients (36%) had only transient increases (concentrations went back to baseline at 72 h), and 16 (31%) had no increases [mean (SD) values

A causal link between human papillomavirus (HPV) infection and cervical cancer has been well established (2,12,14,23). A large number of HPV genotypes have been identified, and the mucosal HPV strains are divided into "high-risk" (HR) and "low-risk" (LR) categories on the basis of their association with cervical lesions. The HR types are more frequently found in premalignant or malignant lesions, LR types are found in benign lesions such as condylomata acuminata (18). Infection by HR HPV types has been demonstrated in almost 100% of cervical carcinoma (29), and it has been recently shown that persistent infection with the same genotype strongly increases the risk of developing high-grade preinvasive disease (11).The detection of HR HPV in cervical samples has been proposed to improve the efficacy of cervical carcinoma screening programs and to triage women with ambiguous or borderline cervical smears (1). Women with persistent HR HPV positivity have a clearly enhanced risk of developing a premalignant lesion and, hence, may be more closely monitored (3,15). Moreover, HR HPV testing may be associated with Pap smear to monitor women who have been treated for high-grade cervical intraepithelial neoplasia (CIN) (16,30). Several studies have revealed that HPV testing yields a high negative predictive value, approaching 100%, for high-grade CIN lesions and cervical carcinomas (lesions Ն CIN3) (21,22,31).Testing for HPV relies on the detection of viral DNA. The only test currently approved by the U.S. Food and Drug Administration for the detection of HPV DNA is the Hybrid Capture 2 (HC2) system (Digene Corporation, Gaithersburg, Md.). The HC2 assay is a ready-to-use test for routine diagnostics and uses a liquid hybridization format followed by signal amplification to detect 13 HR HPV types (i.e., genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) by means of an RNA cocktail probe; the test does not distinguish individual HPV types. The sensitivity is approximately 4,700 viral copies/ml of cervical sample suspension. The evaluation of its laboratory performance has shown that HC2 is a reliable and reproducible test (4,6,8); both characteristics are fundamental for a test with potential widespread use. Different laboratories have also used many PCR-based methods. PCR methods are considered the "gold standard" for analytical sensitivity to detect infectious organisms, including HPV. However, PCRs for HPV detection are currently performed as "home brew" methods, lack standardization, show different sensitivity and specificity, are time-consuming, and require a demanding job for the laboratory. In the last years, some studies have compared the performance of HC2 and PCR, showing a good level of agreement between the two methods (19, 28).

Background: Increased cardiac troponin I (cTnI) in patients treated with high-dose chemotherapy (HDCT) for aggressive malignancy has been proposed as an early marker of late HDCT-induced cardiac dysfunction. We investigated whether cTnI measured by the Stratus CS (Dade Behring) would allow detection of minimal cTnI increases in patients treated with HDCT. Methods: Plasma cTnI concentrations were determined in 179 consecutive patients before HDCT, at the end of the treatment, and after 12, 24, 36, and 72 h. Cardiac function was explored by echocardiography, and left ventricular ejection fraction (LVEF) was recorded during follow-up. The greatest variation in LVEF from the baseline value was used as a measure of cardiac damage. Results: In 99 healthy volunteers, the 99th percentile was at 0.07 g/L. On the basis of ROC curve analysis (area under the curve, 0.89), a cutoff of 0.08 g/L was chosen (sensitivity, 82%; specificity, 77%). cTnI >0.08 g/L occurred in 57 patients (32%) with echocardiographic monitoring revealing a mean decrease in LVEF of 18%. In comparison, the group of cTnI-negative patients had a mean decrease in LVEF of 2.5% (P <0.001). Conclusions: Plasma cTnI, as measured with the Stratus CS, can detect minor myocardial injury in patients treated with HDCT.

Background: Testing for circulating biomarkers in lung cancer is hampered by the insufficient specificity. We aimed to assess the relative diagnostic accuracy of pro-gastrin-releasing peptide (ProGRP) for the differential diagnosis of small cell lung cancer and compare it with more conventional biomarkers. Methods: We enrolled a cohort of 390 patients with a clinical suspicion of lung cancer and for whom a histologic assessment was available. Serum or plasma samples were assessed for ProGRP, carcinoembryonic antigen, CYFRA 21-2, and neuron-specific enolase. The performance of each biomarker in discriminating the small cell lung cancer and squamous cell carcinoma/adenocarcinoma from non-malignant lung disease, and small cell lung cancer from squamous cell carcinoma/adenocarcinoma, was assayed by receiver operating characteristic curve analysis. Results: At the cut-off levels suggested by the manufacturers, ProGRP and neuron-specific enolase showed an almost identical sensitivity of 55.2% and 55.6%, respectively, in discriminating small cell lung cancer with respect to non-malignant lung disease. In order to quantify the added value of ProGRP to other conventional markers, we ran a multivariable logistic regression analysis, but the results showed that no markers improve the performance of ProGRP. Conclusions: ProGRP and neuron-specific enolase individually appear more accurate than other conventional biomarkers for small cell lung cancer, but the union of two markers does not increase the accuracy. The very small target group of patients with small cell lung cancer is a limitation of this study, which can explain why ProGRP alone does not show a sensitivity higher than neuron-specific enolase, as reported by other authors.

The serial monitoring of cardiac troponin represents an effective approach for the early identification, assessment, and monitoring of chemotherapy-induced cardiac injury. Over the last few years new generations of troponin assays, referred to as sensitive and high sensitivity assays, able to detect very low concentrations of troponin, have been progressively released on different platforms. Some studies have assessed the comparability of the cTnI measurements with the new assays versus the conventional ones, but none of these in the oncological population. We compared the cTnI results determined on Stratus CS and ADVIA Centaur CP System in 70 breast cancer patients, for a total of 327 samples collected during different cycles of treatment. Correlation (Spearman = 0.732) and agreement (91.4%) between the assays were good (244 concordant negatives and 55 concordant positives), with a frequency of 8.6% discordant results among the cTnI measurements. Despite the well-known lack in the harmonization and standardization of the currently commercially available cTnI methods, we found a good clinical concordance of cTnI determination on both systems.