Claudia Mazzarella

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA.

Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers.

Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer.

Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy.

Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa.

Enhancement of Vascular Endothelial Function by Recombinant Human Thyrotropin

CONTEXT The cardiovascular consequences of thyroid diseases are attributed to the altered secretion of thyroid hormones. The possibility that TSH also affects the cardiovascular system has been poorly explored. Endothelial cells and vascular smooth muscle cells possess TSH receptors. OBJECTIVE The study was designed to determine whether TSH exerts any effect on vascular homeostasis. SUBJECTS AND METHODS Two different double-blind, controlled studies were performed, one in eight healthy volunteers and the other in six thyroidectomized patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1 mU/min) to raise TSH to severe hypothyroidism levels (approximately 100 microU/ml). Endothelium-dependent and -independent vasodilation was tested by intraarterial infusion of acetylcholine and sodium nitroprusside, respectively, and forearm blood flow was measured by plethysmography. RESULTS Endothelium-dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment effect; general linear model). The dynamics of the response was also profoundly affected by rhTSH because the dose-response curve was much steeper than in controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had no effect on endothelium-independent vasodilation (P = NS for both treatment and interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3 +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated endothelium-mediated vasodilation to an extent similar to that of healthy subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction), without affecting the response to nitroprusside. In these patients, thyroid hormones remained unchanged during rhTSH infusion. CONCLUSIONS rhTSH exerts marked effects on the resistance vessels by enhancing endothelial-mediated vasodilation, independent of changes in thyroid hormone concentration.

Salvage Radical Prostatectomy after External Beam Radiation Therapy: A Systematic Review of Current Approaches

Background: Radical external beam radiotherapy (EBRT) is a standard treatment for prostate cancer patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. For these patients, local salvage therapy such as radical prostatectomy, cryotherapy, and brachytherapy may be indicated. Objective: The objectives of this review were to analyze the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. Methods: A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. Results: Most studies demonstrated that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. Conclusions: Our results suggest that for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis. An improvement in selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological outcome and least comorbidity.

Could High Levels of Tissue Polypeptide Specific Antigen, a Marker of Apoptosis Detected in Nonalcoholic Steatohepatitis, Improve after Weight Loss?

Background: Tissue Polypeptide Specific antigen has recently been proposed as diagnostic marker of apoptosis in NonAlcoholic SteatoHepatitis. The aim of this study was to validate in patients suffering from NonAlcoholic SteatoHepatitis the clinical utility of this marker after different programs of weight reduction. Methods: Overweight/obese patients with visceral adiposity and liver histology compatible were assigned to a Calorically-Restricted diet (n = 22), a Calorically-Restricted diet plus EXercise (n = 19) or No Healthy Life Style (control group, n = 21) for six months. The presence of Body-Weight loss was assessed by a Body Mass Index decrease of at least three points. Serum ALanine aminoTransferase, HOmeostasis Model Assessment method value and Tissue Polypeptide Specific antigen concentrations were determined at time 0, after 3 and 6 months in both the Intervention groups and in the controls’ one. Results: In NonAlcoholic SteatoHepatitis patients who obtained Body-Weight reduction, a significant decrease of the serum Tissue Polypeptide Specific antigen values was showed with a clear linear trend across time, P = 0.0001. Decrement of Tissue Polypeptide Specific antigen concentrations best differentiated the Body-Weight loss from the body-weight maintenance in respect to Tissue Polypeptide Specific antigen and HOmeostasis Model Assessment method values. Conclusion: This study support the clinical utility of serum Tissue Polypeptide Specific antigen antigen levels in the follow-up of overweight/obese patients with NonAlcoholic SteatoHepatitis on weight reduction programs.

Preoperative insulin-like growth factor-binding protein-3 (IGFBP-3) blood level predicts gleason sum upgrading.

About 43% of men with low Gleason grade prostate cancer (PCa) at biopsy will be finally diagnosed with high‐grade PCa at radical prostatectomy (RP). Gleason sum at RP is a good indicator of biochemical recurrence and poor clinical outcome. Therefore, there is a need to improve clinical evaluation of PCa aggressiveness in order to choice appropriate treatment. To this aim an easy‐available tool is represented by circulating biomarkers. Among these, the best candidates are some molecules involved in PCa pathogenesis such as IGFBP‐2 and IGFBP‐3, IL‐6, and its soluble receptor (SIL‐6R).

HIGH HE4 CYSTIC FLUID/SERUM RATIO: A PREDICTOR OF MALIGNANCY IN PANCREATIC CYSTIC LESION? A CASE REPORT.

Vincenzo Napolitano 1 , Claudia Mazzarella 2 , Augusta Moccia 2 , Manuela Avellino 1 , Melania D’Anna 3 , Giuseppe Perruolo 2 , Giuseppe Portella 2 and Daniela Terracciano 2 . 1. Department of Anaesthesiology, Surgery and Emergency Sciences, Second University of Naples, Italy. 2. Department of Translational Medical Sciences, University of Naples Federico II, Italy. 3. Department of Public Health, Pathology Division, University of Naples Federico II, Italy. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History