This Month in Investigative Urology

Article Outline

• Imaging of Calcium Urolithiasis Using Fluorescence
• Intravesical Nanocrystalline Silver for Bladder Inflammation
• Electrical Impedance Spectroscopy of Prostatic Tissues
• PCA3: A Urine Assay That Predicts Prostate Biopsy Outcome
• Transforming Growth Factor-β1 as Predictor of Biochemical Progression After Radical Prostatectomy
• Copyright

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Imaging of Calcium Urolithiasis Using Fluorescence 

In the surgical management of urolithiasis the goal is not only to remove calculi but also to prevent future stone formation by rendering the patient stone-free/fragment-free. Achieving this goal is often difficult with endoscopic procedures due to the inability to visualize small calculi well even with x-ray or ultrasound. Figueiredo et al (page 1610) from Boston, Massachusetts evaluated fluorescence probes as a method of identifying calculi in the urinary tract. In vitro calcium stones were incubated with each of the Osteosense™ 680 and Osteosense 750 calcium binding fluorescence probes, and imaged with a near infrared fluorescence imaging system. Using a mouse model calculi were placed in the renal pelvis and the probes were injected intravenously. Imaging was performed at various times after injection. In vivo intravenous administration of the probes was successful in labeling all calcium stone types tested. Fluorescence imaging provides a new method for the identification of calculi in the urinary tract. The improved visualization of these calculi would make endoscopic procedures less difficult, decrease the risk of complications and increase the chance of rendering the patient stone-free/fragment-free.

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Intravesical Nanocrystalline Silver for Bladder Inflammation 

Interstitial cystitis is a sterile bladder inflammatory disease characterized by pelvic pain, urinary urgency and frequency. Nanocrystalline silver (NCS) particles have recently been investigated in many inflammatory processes. NCS (1%) cream significantly decreased swelling and inflammation, including TNF-α gene expression, in an experimental animal model of dermatitis, and it has also been shown to promote wound healing. Currently NCS is clinically available as an impregnated wound dressing used for patients with burns. Boucher et al (page 1598) from Boston, Massachusetts examined the effect of intravesical NCS in an established animal model of bladder inflammation using protamine sulfate and bacterial lipopolysaccharide to investigate it as a potential treatment for interstitial cystitis. NCS at varying concentrations or phosphate buffered saline was introduced intravesically in female rat bladders followed by vehicle or protamine sulfate and lipopolysaccharide. Urine was collected throughout for histamine assay. The catheter was removed, the rat was returned to its cage and later it was sacrificed. The bladder was harvested, minced and cultured overnight, and the medium was collected for TNF-α assay. Intravesical administration of NCS (1%) significantly reduced protamine sulfate/lipopolysaccharide induced rat total urine histamine and bladder explant TNF-α release. NCS also decreased bladder mast cell infiltration and degranulation. Intravesical instillation of NCS may in the future provide an alternative or additive treatment for interstitial cystitis.

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Electrical Impedance Spectroscopy of Prostatic Tissues 

The specificity of current screening methods for prostate cancer is limited and results in approximately 75% to 80% of patients who undergo biopsy having findings negative for cancer. Halter et al (page 1580) from Hanover, New Hampshire used electrical impedance spectroscopy to evaluate how significantly the electrical properties of benign and malignant prostatic tissues differ with the goal of providing clinicians with a new tool to aid in diagnosis. Freshly excised prostates immediately following radical prostatectomy were collected and sectioned into 3 mm slices. Electrical property measurements of conductivity and relative permittivity were recorded from each slice using a coaxially configured probe over the frequency range of 1 kHz to 1 MHz. The area probed was marked so that after tissue fixation and slide preparation histological assessment could be correlated directly with the recorded electrical impedance spectroscopy spectra. Prostatic adenocarcinoma, benign prostatic hyperplasia (BPH), nonhyperplastic glandular tissue and stroma were the primary tissue types probed with electrical impedance spectroscopy. There were significant conductivity differences between cancer and stroma at all frequencies. There were also significant permittivity differences between cancer and BPH. Significant correlations were observed between electrical properties, and the concentration of stromal and glandular tissues present in the histologically assessed tissue area. The electrical properties of benign and malignant prostate tissues differ significantly, and should be considered for use as a diagnostic tool. The differences observed between cancer and BPH are especially important since current screening methods do not reliably differentiate between the 2 conditions.

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PCA3: A Urine Assay That Predicts Prostate Biopsy Outcome 

Prostate cancer gene 3 (PCA3) is a new molecular marker that has shown promise for improving the diagnosis of prostate cancer. PCA3 is a prostate specific noncoding mRNA that is over expressed 60 to 100-fold in more than 90% of prostate tumors compared to benign prostatic tissue. The over expression of PCA3 mRNA can be quantified and expressed relative to a prostate specific gene that is not altered in expression in cancer cells. In several studies the urine test for PCA3 was found to be superior to the serum prostate specific antigen (PSA) test for predicting the outcome in men undergoing first or repeat biopsy. Deras et al (page 1587) from San Diego, California assessed the performance of the PCA3 assay in men scheduled for prostate biopsy. The PCA3 score was investigated with respect to prostate volume, serum PSA and biopsy result. The ability of the PCA3 score to synergize with other clinical information to predict biopsy outcome was also examined.

Prospectively urine was collected following standardized digital rectal examination in 570 men immediately before prostate biopsy. Urinary PCA3 mRNA levels were quantified and then normalized to the amount of prostate derived RNA to generate a PCA3 score. PCA3 is independent of prostate volume, serum PSA and number of prior biopsies. The quantitative PCA3 score correlated with the probability of positive biopsy. Logistic regression results suggest that the PCA3 score could be incorporated into a nomogram for improved prediction of biopsy outcome. The results of this study provide further evidence that PCA3 is a useful adjunct to current methods of prostate cancer diagnosis.

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Transforming Growth Factor-β₁ as Predictor of Biochemical Progression After Radical Prostatectomy 

It has been shown that plasma levels of transforming growth factor-β₁ (TGFβ₁) as well as interleukin 6 (IL-6) and its soluble receptor IL6sR are associated with established features of aggressive primary prostate cancer with clinically evident and occult metastases present at primary treatment and with eventual disease progression. However, for biomarkers to be clinically useful they must add unique predictive information to an established prognostic model in a clinically and statistically meaningful fashion. To date these are the only blood based biomarkers that improve the accuracy of the preoperative Kattan nomogram for predicting biochemical progression after radical prostatectomy. There have been no reports of blood based biomarkers capable of improving the accuracy of pathological features after radical prostatectomy (Kattan postoperative nomogram) for predicting biochemical progression.

Shariat et al (page 1593) from Dallas, Texas hypothesized that patients with increased plasma levels of TGFβ_1, IL-6 and/or IL6sR after radical prostatectomy would be more likely to harbor occult metastases leading to disease progression despite effective local control of disease. Plasma levels of TGFβ₁, IL-6 and IL6sR were measured 6 to 8 weeks after surgery in 291 consecutive patients treated with radical prostatectomy for clinically localized disease. On multivariate analysis adjusting for standard postoperative features, postoperative plasma TGFβ₁ was the only biomarker independently associated with biochemical progression. Of patients who experienced biochemical progression, postoperative TGFβ₁ was significantly higher in those with features of aggressive disease progression (ie development of metastasis, PSA doubling time less than 10 months and/or failure to respond to local salvage radiation therapy). Postoperative IL-6 and IL6sR showed limited clinical usefulness in prostate cancer.