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Objective: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. Materials and Methods: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. Results: Evidence from the selected studies were used to form evidencebased guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. Conclusions: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. Hypercalciuria: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. Hyperoxaluria: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. Hyperuricosuria: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. Hypocitraturia: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. Children: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. Elderly: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

Background: Approximately 40% of males with low Gleason grade clinically localized prostate cancer (PCa) at biopsy were finally diagnosed with high Gleason grade PCa at radical prostatectomy (RP). Therefore, a more reliable assessment of the Gleason grade prior to RP is required. Readily available modalities such as circulating biomarkers may be useful for this purpose. The aim of this study was to evaluate the ability of preoperative interleukin 6 (IL-6) and its soluble receptor (sIL-6R), as well as urokinase-type plasminogen activator (u- PA), its receptor (u-PAR) and the inhibitor (PAI-1) to predict Gleason score upgrading. Patients and Methods: A total of 51 PCa patients with biopsy Gleason score ≤7 were studied. Preoperative serum samples were collected prior to digital rectal examination (DRE) and TRUS. Blood was collected into non-heparinized tubes and serum was separated within 1 h of blood collection. The serum was stored at –80˚C and then thawed just prior to testing. Serum levels of PSA, free-PSA and IL-6 were measured using the Immulite 2000 automated assay (DPC, Los Angeles, CA, USA). The concentrations of sIL-6R (R&D Systems, Minneapolis, MN, USA), uPA, uPAR and PAI- 1 (Assaypro, Winfield, MO, USA) in serum were determined according to the manufacturer’s instructions using the ELISA test. Every sample was run in duplicate and the mean was used. The differences between the two measurements were minimal. Results: GS upgrading was defined as a Gleason sum increase between biopsy and RP from ≤7 to >7, since this is important for the therapeutic strategy. On this basis, an upgrade was noted in 5 (10%) samples. Median sIL-6R values were found to be significantly higher in patients with GS upgrading (difference in medians, 28.40 ng/ml; 95% CI, 5.60-49.44; p=0.024). The association between sIL-6R and GS upgrading became more significant by using the sIL-6R/IL-6 ratio (difference in medians, 7.77; 95% CI, 1.72-11.28; p=0.011). Sensitivity and specificity of sIL-6R and the sIL-6R/IL-6 ratio were explored by ROC curve analysis (Figure 1). Figure 1. ROC analysis comparing sIL-6R (--) and sIL-6R/IL-6 ratio (–). The results indicated an extremely good ability to predict the probability of biopsy Gleason sum upgrading of the two parameters (sIL-6R: AUC=0.80; 95% CI, 0.63-0.97; p=0.026. sIL-6R/IL-6 ratio: AUC=0.84; 95% CI, 0.69-0.98; p=0.014). The optimal cut-off point for sIL-6R was 76.5 ng/ml, providing a sensitivity of 80% and a specificity of 76%, whereas for the sIL-6R/IL-6 ratio the optimal cut-off point was 13.5 with comparable sensitivity (80%), but higher specificity (83%). Discussion and Conclusion: sIL-6R may be a significant circulating biomarker employed to predict GS upgrading in patients with a biopsy GS ≤7. Moreover, this ability appears to be enhanced by calculating the sIL-6R/IL-6 ratio. These findings may provide an additional ‘staging tool’ for PCa patients, which may be of great significance in guiding clinicians’ treatment choices, according to current guidelines. 1 Shariat SF, Andrews B, Kattan MW, Kim J, Wheeler TM and Slawin KM: Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis. Urology 58: 1008-1015, 2001. 2 Spiotto MT and Chung TD: STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells. Prostate 42: 186-195, 2000. 3 Deeble PD, Murphy DJ, Parsons SJ and Cox ME: Interleukin-6-and cyclic AMP-mediated signaling potentiates neuroendocrine differentiation of LNCaP prostate tumor cells. Mol Cell Biol 21: 84718482, 2001.

A group of 107 patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE) participated to the HOUSE Study (Home and Office Uroflowmetry Specific Evaluation). Patients received routine investigation, consisting of medical history taking, physical examination including digital rectal examination, prostate-specific antigen (PSA), assessment of symptoms listed both on the International Prostate Symptom Score and on ICS-male questionnaire. We examined the results of uroflowmetry evaluation in this population; data were analysed to observe if any circadian changes of parameters obtained with home uroflowmetry could be detected. We searched a correlation between Q(max), Q(ave) and ICS-benign prostatic hyperplasia symptom score: a significantly inverse correlation was found only for Q(max), confirming Q(max) as a reliable parameter to quantify subjective symptoms. When examining the multiple flow curves recorded in the same patient with home uroflowmetry, voided volume and flow time had usually higher values during night-time: the existence of circadian changes of uroflowmetry parameters in patients with LUTS from BPE was confirmed, and lower values of average and maximum flow rates during sleep hours were recorded in the same patient. In conclusion, when evaluating the natural history or treatment outcome of individual patients or group of patients in clinical trials for evaluation of BPE and LUTS, an assessment including multiple measurements may be useful and of value.

We treated primary epithelial cells from human normal prostate (NEPC) and prostate cancer (CEPC) with all-trans-retinoic acid (RA) to study whether it regulates the activity of tissue transglutaminase (tTGase), an enzyme that accumulates in cells undergoing apoptosis. tTGase activity was assessed by [14C]spermidine incorporation; tTGase, P53, Bcl-2, and p21 protein levels were evaluated by Western blotting; and RA receptors (RAR alpha, -beta, and -gamma), tTGase, retinol-binding protein (RBP), and cellular RBP type I transcripts were determined by semiquantitative RT-PCR. After 72-96 h of 10(-6) mol/L RA treatment, cell growth inhibition and apoptosis were associated with increased tTGase activity in both NEPC and CEPC, and with increased tTGase protein and messenger ribonucleic acid levels only in NEPC. Moreover, RA down-regulated RAR alpha and -beta and increased RBP messenger ribonucleic acid levels in NEPC, whereas it increased RAR beta gene expression and decreased Bcl-2 protein levels in CEPC. Our results suggest that RA induces tTGase gene expression and enzyme activity in normal prostate cells, and that RA-regulated pathways are impaired in cancer cells. Moreover, down-regulation of Bcl-2 protein and up-regulation of RAR beta suggest that retinoid may act on the genetic defect responsible for prostate cancer progression.