This Month in Investigative Urology

Article Outline

• Optical Reflectance Spectroscopy to Differentiate Renal Tumor From Normal Parenchyma
• A Novel Radial Dilating Balloon Ureteral Access Sheath
• A Noninvasive Method for Cystometric Evaluation in Mice
• Mismatch Repair Gene MSH3 Polymorphism May be a Risk Factor for Prostate Cancer
• The Arachidonic Acid Pathway and its Role in Prostate Cancer
• PIK3CA, HRAS and KRAS Gene Mutations in Human Penile Cancer
• Copyright

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Optical Reflectance Spectroscopy to Differentiate Renal Tumor From Normal Parenchyma 

Optical spectroscopy is a noninvasive technique that uses light interaction with tissue to obtain information about the structure and the function of the tissue. Promising results have been reported with the use of optical spectroscopy for in vitro and ex vivo assessment of various solid tumors. Bensalah et al (page 2010) from Dallas, Texas investigated the ability of optical reflectance spectroscopy to differentiate between normal parenchyma and tumor tissue in renal specimens removed at surgery. There was also a specific focus on a subset of partial nephrectomy specimens to assess whether optical reflectance spectroscopy could detect a positive resection margin. Optical reflectance spectroscopy measurements were completed at standardized tumor and normal parenchymal locations immediately after kidney tumor removal. The slopes of the optical reflectance spectroscopy curves were compared, and the correlation between tumor and normal parenchyma reflectance was assessed. A significant difference was noted between the average optical reflectance spectroscopy slopes of tumor and normal parenchyma. In individual radical nephrectomy specimens optical reflectance spectroscopy measurements at different locations in the tumor showed an excellent correlation. Normal parenchymal measurements also correlated well. In the partial nephrectomy subset a close correlation was found among measurements made on the normal parenchymal margin of the tumor. Optical reflectance spectroscopy can help distinguish tumor from normal renal tissue in specimens immediately removed at surgery. Optical reflectance spectroscopy may allow real-time assessment of positive margins during partial nephrectomy.

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A Novel Radial Dilating Balloon Ureteral Access Sheath 

All ureteral access sheaths currently on the market rely on the Dotter principal of axial force for dilatation during insertion. This axial dilation is potentially traumatic to the ureter and results in failure to place the sheath in up to a third of patients. A new ureteral access sheath has been developed that uses a new concept in sheath placement. The new balloon expandable sheath inserts with radial dilatation, a technology that could circumvent the shearing force to the urothelium caused by axial dilatation. Harper et al (page 2042) from Loma Linda, California compared a novel balloon expandable ureteral access sheath using radial dilation to a conventional ureteral access sheath in a porcine model. Pigs underwent randomized placement of the novel sheath in one ureter and a conventional ureteral access sheath in the contralateral ureter followed by videotaped ureteroscopy. Acute study end points included maximum and mean force of sheath insertion and removal, saline flow rate, and subjective urothelial damage following sheath insertion/inflation. Additionally, blinded reviewers rated urothelial damage on digitally recorded video following sheath removal. Chronic data included gross and histological ureteral analysis at 30 days. The novel balloon expandable ureteral access sheaths had easier insertion and a better flow rate, and caused less urothelial trauma in this porcine model. The ureteral access sheath offers a promising new option for ureteral access.

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A Noninvasive Method for Cystometric Evaluation in Mice 

Hodges et al (page 2046) from Winston-Salem, North Carolina presented a simple method for identifying and evaluating altered bladder function in mice that could facilitate a noninvasive and higher throughput evaluation of the causes of bladder storage conditions, thus facilitating the identification of novel therapies. The investigators used bladder function in male and female wild type and uroplakin II knockout mice using a filter paper assay to compare ultraviolet visualization of voiding patterns with cystometric parameter estimates obtained on these same mice. The uroplakin II knockout mice were used because the absence of uroplakin II has been associated with lower urinary tract dysfunction including the presence of detrusor overactivity. The voiding pattern markings were graded by independent observers on a scale of 1 to 5 according to the degree of dispersion of voided urine. Statistical analysis was then used to correlate voiding dispersion grades with cystometric parameters in the same mice. Ultraviolet visualization of urinary voiding patterns may provide a simple, noninvasive method of evaluating mouse bladder function/dysfunction. Implementation of this methodology, which can potentially be automated for high throughput analysis, can accelerate the development of novel therapy for certain important aspects of bladder disease.

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Mismatch Repair Gene MSH3 Polymorphism May be a Risk Factor for Prostate Cancer 

The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in mismatch repair proteins have up to a 1,000-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. In the mismatch repair system there are 7 mismatch repair genes including MSH3 and MSH6. Hirata et al (page 2020) from San Francisco, California hypothesized that polymorphisms of mismatch repair genes could be a risk factor for prostate cancer and that p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. To test this hypothesis the investigators examined whether polymorphisms in MSH3 and MSH6 genes are associated with prostate cancer, and investigated the additional effect of p53 Pro/Pro on MSH3 and MSH6 gene polymorphisms. DNA samples from 110 cases of prostate cancer and 110 healthy controls were analyzed to determine the genotypic frequency of 5 polymorphic loci on 2 mismatch repair genes (MSH3 and MSH6) and p53 codon72. The investigators found that the MSH3 polymorphism may be a risk factor for prostate cancer.

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The Arachidonic Acid Pathway and its Role in Prostate Cancer 

The arachidonic acid pathway incorporates phospholipase, cyclooxygenase, lipoxygenase and epoxygenase enzymes. This pathway has been shown to have a major role in the development and progression of a number of cancers including prostate cancer. In a review article Patel et al (page 1668) from Sydney, New South Wales, Australia discuss the current status of research on this pathway in the area of prostate cancer, ranging from preclinical in vitro studies to human clinical trials. Epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs may decrease the risk of prostate cancer. This effect, presumably through the inhibition of cyclooxygenase-2, has been validated in preclinical studies. Cyclooxygenase-2 inhibition has also decreased the rate of prostate specific antigen increase in men with biochemical recurrence after treatment for prostate cancer. Although lipoxygenase and secretory phospholipase A2 inhibition is also effective for decreasing prostate cancer growth in preclinical studies, these strategies have not yet been used in clinical trials. Cytosolic phospholipase A2, platelet activating factor and epoxygenase need further investigation to determine a role in prostate cancer. Evolving data suggest a significant role for some areas of the arachidonic acid pathway in prostate cancer. Inhibition of 1 or a number of these enzymes in combination may hold promise for future prostate cancer treatment.

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PIK3CA, HRAS and KRAS Gene Mutations in Human Penile Cancer 

Alterations in the signaling pathways downstream of growth receptors with tyrosine kinase activity are emerging to be one of the most common events in various cancers. This is in part because these receptors control 2 major signaling pathways, that is phosphatidylinositol 3-kinase (PI3K) and the Ras pathway, both of which have been well studied in many cancer types. Andersson et al (page 2030) from Linkoping, Sweden examined the dysregulation of components in the PI3K and Ras pathways. Using single stranded conformational analysis, mutation analysis of genes was performed in 28 penile tumors. Somatic missense mutations were identified in 39% of the penile cancer samples. In the PIK3CA gene 8 mutations (29%) were identified. The PIK3CA mutations were found in all grades and stages, whereas the HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.