Preanalytical stability of [-2]proPSA in whole blood stored at room temperature before separation of serum and plasma: implications to Phi determination.

Background [-2]proPSA seems to outperform free/total prostate-specific antigen (PSA) ratio in prostate cancer diagnosis. However, [-2]proPSA stability remains an underestimated issue. We examined [-2]proPSA stability over time in whole blood before separation of serum and plasma and its implications for prostate health index (Phi) determination. Total PSA (tPSA) and free PSA (fPSA) stabilities were also assessed. Methods Blood was drawn from 26 patients and separated in two tubes for plasma (K2EDTA and K2EDTA plus protease inhibitors - P100) and one for serum (clot activator plus gel separator). Tubes were stored at room temperature before centrifugation 1, 3 and 5 h for serum and EDTA plasma or 1 and 5 h for P100 plasma. To investigate the influence of gel separator on markers' stability, blood was collected from 10 patients in three types of tubes to obtain serum: tubes with clot activator plus gel separator, with silica particles or glass tubes. Biomarkers were assayed with chemiluminescent immunoassays. Results [-2]proPSA and Phi levels significantly and progressively increased over time in serum (+4.81% and +8.2% at 3 h; +12.03% and +14.91% at 5 h, respectively, vs. 1 h; p<0.001). Conversely, [-2]proPSA levels did not change in plasma (EDTA or P100). tPSA levels did not change over time in serum or plasma, whereas fPSA decreased in serum. All markers were higher in plasma than in serum at any time point. This difference did not seem to be attributable to the use of gel for serum preparation. Conclusions EDTA prevented spurious in vitro modifications in PSA-related isoforms, confirming that a stabilized blood sample is a prerequisite for [-2]proPSA measurement and Phi determination.

Phytosome complex of curcumin as complementary therapy of advanced pancreatic cancer improves safety and efficacy of gemcitabine: Results of a prospective phase II trial.

A large body of biomedical evidence indicates that activation of Nrf2 by curcumin increases the nucleophilic tone and damps inflammation cumulatively supporting the malignant phenotype. Conversely, genetic analyses suggest a possible oncogenic nature of constitutive Nrf2 activation since an increased nucleophilic tone is alleged increasing chemoresistance of cancer cells. Aiming to contribute to solve this paradox, this study addressed the issue of safety and efficacy of curcumin as complementary therapy of gemcitabine on pancreatic cancer. This was a single centre, single arm prospective phase II trial. Patients received gemcitabine and Meriva®, a patented preparation of curcumin complexed with phospholipids. Primary endpoint was response rate, secondary endpoints were progression free survival, overall survival, tolerability and quality of life. Analysis of inflammatory biomarkers was also carried out. Fifty-two consecutive patients were enrolled. Forty-four (13 locally advanced and 31 metastatic) were suitable for primary endpoint evaluation. Median age was 66 years (range 42-87); 42 patients had Eastern Cooperative Oncology Group performance status 0-1. The median number of treatment cycle was 4.5 (range 2-14). We observed 27.3% of response rate and 34.1% of cases with stable disease, totalizing a disease control rate of 61.4%. The median progression free survival and overall survival were 8.4 and 10.2 months, respectively. Higher IL-6 and sCD40L levels before treatment were associated to a worse overall survival (p < 0.01). Increases in sCD40L levels after 1 cycle of chemotherapy were associated with a reduced response to the therapy. Grade 3/4 toxicity was observed (neutropenia, 38.6%; anemia, 6.8%). There were no significant changes in quality of life during therapy. In conclusion, the complementary therapy to gemcitabine with phytosome complex of curcumin is not only safe but also efficiently translate in a good response rate in first line therapy of advanced pancreatic cancer.

Indicators of inappropriate tumour marker use through the mining of electronic health records.

RATIONALE, AIMS, AND OBJECTIVES: Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs). METHODS: Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy. Evidence-based criteria were used to develop performance indicators. Demographic and clinical information associated with TM orders were examined. RESULTS: A total of 80 813 TMs were ordered in 52 536 outpatients (1.54 markers/patient). Indicators related to disease codes, gender, age, and TM repetitions were developed, and their application showed that (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and 65.6%) whereas the other TMs are largely requested also in patients without cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are negligible; (3) although requests in people older than 80 years are relevant (16.4% of total), the highest rate of request of all markers occurs in patients aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69 years; (5) <50% of PSA orders are associated with cancer code for all age intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA are prevalent in cancer patients or benign diseases to which TMs are appropriate, whereas PSA repetitions occur mainly in patients without cancer. CONCLUSIONS: The developed indicators resulted suitable to monitor TM overordering in outpatients through the mining of EHRs. The present study is a first approach towards the use of big-data mining for TM appropriateness evaluation purposes.

Evaluating serum insulin-like growth factor 1 and insulin-like growth factor binding protein 3 as markers in prostate cancer diagnosis.

BACKGROUND: Prostate-specific antigen (PSA) lacks specificity and sensitivity in discriminating prostate cancer (PCa) from benign prostatic hyperplasia (BPH) when the total PSA (tPSA) level is between 4 and 10 ng/mL. It remains to be investigated if additional tumor-associated molecules may improve the PCa diagnostic accuracy. The aim of the present study was to investigate whether serum levels of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3) and their combinations with PSA may enhance the diagnosis of PCa. METHODS: Serum tPSA and free PSA (fPSA) levels were measured using an automated chemiluminescence-based method. IGF1 and IGFBP3 levels were evaluated by radioimmunoassays in a prospectively and consecutively enrolled subset of 149 patients with tPSA ≤10 ng/mL made up of patients with benign prostatic hyperplasia (BPH; n = 113) and PCa (n = 36). RESULTS: IGF1 and IGFBP3 serum levels did not significantly differ between the PCa and BPH groups. No important correlation was found between the IGF molecules and PSA isoforms in both groups. Statistical analysis of the combination of markers indicated that only the free/total PSA ratio (f/tPSA%) was informative and independent in predicting the presence of PCa, considering that for high values of this percentage (17%) the probability of finding PCa decreased. Receiver operating characteristics areas under the curve (AUC) for IGF1 and IGFBP3 were not informative (AUC ~0.5 in both cases) contrary to the AUC for f/tPSA% (AUC = 0.689, p = 0.0002). CONCLUSIONS: The present study showed that neither IGF1 and IGFBP3 alone nor in combination with PSA enhance the diagnostic performance of PSA in PCa.