this month in investigative urology

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This Month in Investigative Urology BIODEGRADABLE URETERAL STENTS AFTER RETROGRADE ENDOPYELOTOMY Biodegradable polymers play an increasingly important role in various medical applications. Olweny et al (page 2198) from Chapel Hill, North Carolina were interested in determining whether a bioabsorbable stent was suitable for use in the upper urinary tract after performing endoscopic retrograde endopyelotomy. A major advantage of using a self-expanding bioabsorbable stent would be the elimination of a second endourological procedure for stent removal at the end of the treatment period and the presumed elimination of any bladder irritation or ureteral reflux. The authors evaluate the use of a self-reinforced poly-L-lactide-co-glycolide bioabsorbable ureteral stent following unilateral Acucise (Applied Medical Resources, Laguna Hills, California) endopyelotomy in 9 female Yucatan minipigs. Self-reinforced PLGA stents were placed in 5 animals (group 1) and 7F double pigtail stents were placed in 4 animals (group 2). Side specific creatinine clearances were similar to preoperative values at 6 and 12 weeks. Flow rates and healing scores were statistically similar for both groups but the latter trended toward less favorable healing of ureteral musculature with application of the absorbable stent. The use of self-reinforced PLGA biodegradable ureteral stents is feasible after Acucise endopyelotomy in a porcine model, with relatively similar radiographic and fluid flow results to standard 7F stents, but with less favorably biocompatibility. TISSUE SEALANT MAY BE PROTECTIVE AGAINST HEMORRHAGE Petratos et al (page 2222) from New York, New York evaluate the efficacy of a cross linked matrix tissue sealant compared to oxidized cellulose and electrocautery in an acute renal injury model. Partial nephrectomy was performed in rats following intravenous heparin anticoagulation. The cut surface received either no treatment, cross linked matrix tissue sealant, electrocautery or oxidized cellulose. Blood pressure was continu- ally monitored, survival time was determined and total blood loss was quantified for each animal. Animals that received no treatment, electrocautery or oxidized cellulose died within 13 minutes of injury, with a decline in blood pressure to 0. Hemostasis was immediate in cross linked matrix treated rats, resulting in no blood loss, and the mean arterial pressure was maintained at normal levels. The cross linked matrix tissue sealant provided immediate hemostasis and protection from decline in blood pressure after renal trauma in heparinized rats. The use of cross linked matrix tissue sealant may benefit patients with severe renal injuries and, in the future, it may be useful in long-term partial nephrectomy repair. VITAMIN D RECEPTOR GENE POLYMORPHISM IS ASSOCIATED WITH UROLITHIASIS Recent studies have suggested that allelic variations of the vitamin D receptor (VDR) gene can influence calcium absorption and excretion. Nishijima et al (page 2188) from Okinawa, Japan studied the association of VDR gene polymorphism with urolithiasis in 83 patients with urinary stones and 83 controls. Cases were scored for long axis diameter of the largest stone, 2) number of stones and 3) history of calcium stone disease, and were then classified into 3 groups according to the total score (low, intermediate or high). Two VDR gene polymor- phisms (Taql and Apal) were detected by polymerase chain reaction-restriction fragment length polymorphism analysis, and their relationship with urinary calcium levels was examined. The frequencies of the Taql Tt and tt genotypes were significantly higher in the high score group than in controls, and the Taql t allele was associated with a 5.2-fold increase in the risk of severe stone disease. The urinary calcium level in patients with the Tt and tt genotypes was also higher than that in those with the TT genotype. The Apal genotypes showed no difference in frequency between the high score group and controls. The Taql t allele of the VDR gene may be a risk factor for severe and recurrent stone disease. KOHKI TEA MAY HAVE A PROTECTIVE EFFECT ON BLADDER DYSFUNCTION Extracts of the leaves of Engelhardtia chrysolepis, a subtropical plant that grows wild in southern China, have been used medicinally in East Asia for hundreds of years. A standardized extract called Kohki tea is sold over the counter as a sweet-tasting tea shown to confer many beneficial effects on general health. The tea contains antioxidants including several dihydroflavonol glycosides. Results of previous studies have shown that natural products with antioxidant activities provide protective effects on the bladder. Levin et al (page 2260) from Albany, New York attempt to determine if oral pretreatment of rabbits with Kohki tea protected the bladder from the dysfunctions induced by partial outlet obstruction. Rabbits were separated into groups 1 and 2—treated by gavage with Kohki tea, and 3 and 4 —fed distilled water. After 4 weeks of daily 0022-5347/02/1675-1949/0 THE JOURNAL OF UROLOGY ® Vol. 167, 1949 –1951, May 2002 Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION,INC. ® Printed in U.S.A. 1949

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Page 1: This Month in Investigative Urology

This Month in Investigative Urology

BIODEGRADABLE URETERAL STENTS AFTER RETROGRADE ENDOPYELOTOMYBiodegradable polymers play an increasingly important role in various medical applications. Olweny et al

(page 2198) from Chapel Hill, North Carolina were interested in determining whether a bioabsorbable stent wassuitable for use in the upper urinary tract after performing endoscopic retrograde endopyelotomy. A majoradvantage of using a self-expanding bioabsorbable stent would be the elimination of a second endourologicalprocedure for stent removal at the end of the treatment period and the presumed elimination of any bladderirritation or ureteral reflux.

The authors evaluate the use of a self-reinforced poly-L-lactide-co-glycolide bioabsorbable ureteral stentfollowing unilateral Acucise (Applied Medical Resources, Laguna Hills, California) endopyelotomy in 9 femaleYucatan minipigs. Self-reinforced PLGA stents were placed in 5 animals (group 1) and 7F double pigtail stentswere placed in 4 animals (group 2). Side specific creatinine clearances were similar to preoperative values at 6and 12 weeks. Flow rates and healing scores were statistically similar for both groups but the latter trendedtoward less favorable healing of ureteral musculature with application of the absorbable stent. The use ofself-reinforced PLGA biodegradable ureteral stents is feasible after Acucise endopyelotomy in a porcine model,with relatively similar radiographic and fluid flow results to standard 7F stents, but with less favorablybiocompatibility.

TISSUE SEALANT MAY BE PROTECTIVE AGAINST HEMORRHAGEPetratos et al (page 2222) from New York, New York evaluate the efficacy of a cross linked matrix tissue

sealant compared to oxidized cellulose and electrocautery in an acute renal injury model. Partial nephrectomywas performed in rats following intravenous heparin anticoagulation. The cut surface received either notreatment, cross linked matrix tissue sealant, electrocautery or oxidized cellulose. Blood pressure was continu-ally monitored, survival time was determined and total blood loss was quantified for each animal. Animals thatreceived no treatment, electrocautery or oxidized cellulose died within 13 minutes of injury, with a decline inblood pressure to 0. Hemostasis was immediate in cross linked matrix treated rats, resulting in no blood loss, andthe mean arterial pressure was maintained at normal levels. The cross linked matrix tissue sealant providedimmediate hemostasis and protection from decline in blood pressure after renal trauma in heparinized rats. Theuse of cross linked matrix tissue sealant may benefit patients with severe renal injuries and, in the future, it maybe useful in long-term partial nephrectomy repair.

VITAMIN D RECEPTOR GENE POLYMORPHISM IS ASSOCIATED WITHUROLITHIASIS

Recent studies have suggested that allelic variations of the vitamin D receptor (VDR) gene can influencecalcium absorption and excretion. Nishijima et al (page 2188) from Okinawa, Japan studied the association ofVDR gene polymorphism with urolithiasis in 83 patients with urinary stones and 83 controls. Cases were scoredfor long axis diameter of the largest stone, 2) number of stones and 3) history of calcium stone disease, and werethen classified into 3 groups according to the total score (low, intermediate or high). Two VDR gene polymor-phisms (Taql and Apal) were detected by polymerase chain reaction-restriction fragment length polymorphismanalysis, and their relationship with urinary calcium levels was examined. The frequencies of the Taql Tt andtt genotypes were significantly higher in the high score group than in controls, and the Taql t allele wasassociated with a 5.2-fold increase in the risk of severe stone disease. The urinary calcium level in patients withthe Tt and tt genotypes was also higher than that in those with the TT genotype. The Apal genotypes showed nodifference in frequency between the high score group and controls. The Taql t allele of the VDR gene may be arisk factor for severe and recurrent stone disease.

KOHKI TEA MAY HAVE A PROTECTIVE EFFECT ON BLADDER DYSFUNCTIONExtracts of the leaves of Engelhardtia chrysolepis, a subtropical plant that grows wild in southern China, have

been used medicinally in East Asia for hundreds of years. A standardized extract called Kohki tea is sold overthe counter as a sweet-tasting tea shown to confer many beneficial effects on general health. The tea containsantioxidants including several dihydroflavonol glycosides. Results of previous studies have shown that naturalproducts with antioxidant activities provide protective effects on the bladder.

Levin et al (page 2260) from Albany, New York attempt to determine if oral pretreatment of rabbits with Kohkitea protected the bladder from the dysfunctions induced by partial outlet obstruction. Rabbits were separatedinto groups 1 and 2—treated by gavage with Kohki tea, and 3 and 4—fed distilled water. After 4 weeks of daily

0022-5347/02/1675-1949/0THE JOURNAL OF UROLOGY® Vol. 167, 1949–1951, May 2002Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC.® Printed in U.S.A.

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oral administration the bladders were catheterized and cystometry was performed. Moderate outlet obstructionswere created in groups 1 and 3, and sham surgeries were performed in groups 2 and 4. Treatment was continuedfor an additional 4 weeks and cystometry was repeated. The bladder was exposed, excised and weighed, andstrips of the bladder were used for contractility studies. The balance of the bladder was separated and frozen inliquid nitrogen for biochemical analyses.

The bladders of obstructed rabbits fed Kohki tea were significantly more compliant than those of rabbits fedwater. Obstructed rabbits fed Kohki tea showed a significantly higher maximal micturition pressure. Thecontractile responses to all forms of stimulation were reduced by obstruction to a significantly greater degree inthe rabbits not fed tea than in the rabbits fed tea. The SERCA enzyme activity of the bladder was significantlyreduced in the obstructed rabbits fed vehicle but the activity was not reduced in the obstructed rabbits fed Kohkitea. Kohki tea had a significant protective effect on bladder function, contractile responses and bladder biochem-istry in rabbits subjected to moderate to severe partial outlet obstruction.

IS THERE A ROLE FOR PROSTATITIS IN THE PATHOGENESIS OF BPH?Despite the common histopathological finding of chronic inflammation in prostate specimens, any association

between prostatitis and benign prostatic hyperplasia (BPH) or prostate cancer remains to be completelyunderstood. Inflammation of long-standing duration has been associated with a number of hyperplastic humandiseases as well as the development of carcinoma in several organ systems. As a foundation for studyinginflammation as a precursor of other diseases of the prostate, Gerstenbluth et al (page 2267) from Cleveland,Ohio hypothesized that prostatitis may be anatomically related to either BPH or prostate cancer. The authorsexamined whole mount radical prostatectomy specimens to better characterize the prevalence and distributionof chronic inflammation along with its relationship to adenocarcinoma of the prostate as well as BPH. Immu-nohistochemical staining for bcl-2 was performed to determine if an association among prostatitis, BPH andcancer may involve up-regulation of proteins that regulate cell death. The authors found that chronic prostatitisis a common finding in radical prostatectomy specimens. Inflammation was associated with BPH and cancer buthad a greater tendency to be associated with BPH. Bcl-2 was prominently expressed in areas of prostatitis. Thesefindings support a role for prostatitis in the pathogenesis of BPH.

PAN-CADHERIN IS A POSSIBLE BIOMARKER FOR PROSTATE CANCERHigh level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically

active prostate cancer and to determine which individuals with an elevated prostate specific antigen (PSA) orprostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated withdecreased cell adhesion. Wehbi et al (page 2215) from Oklahoma City, Oklahoma studied cadherins as a potentialbiomarker for prostate cancer. Prostate tissues from patients with cancer and controls with a 10-year prostatecancer-free followup were labeled for pan-cadherin by immunohistochemistry. Immunoreactivity was quantifiedusing the Autocyte Pathology Workstation (Autocyte, Inc., Elon College, Alamance, North Carolina). Withquantitative immunohistochemistry 36 of 38 prostate cancer cases expressed lower mean percent area positivefor cadherin than did 19 of 19 BPH and 14 of 14 prostatitis cases. Quantitative down-regulation of cadherinexpression on prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin andother high level phenotypic biomarker expression in the premalignant field may provide additional diagnosticinformation to decide who needs re-biopsy, more intensive monitoring or chemoprevention.

ACTIVATION OF GUANYLATE CYCLASE BY YC-1 CAUSES ERECTILE RESPONSESIN THE RAT

Activation of soluble guanylate cyclase with subsequent increase in intracellular levels of cyclic guanosinemonophosphate is necessary for normal erection. In vascular tissue YC-1 has been shown to stimulate solubleguanylate cyclase independently from nitric oxide. Mizusawa et al (page 2276) from Lund, Sweden attempt todetermine if YC-1 could modulate erectile responses in the rat. The effects of YC-1 given intracavernously orintraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronaland endothelial nitric oxide relaxations were studied in noradrenaline contracted preparations of rat isolatedcorpus cavernosum. YC-1 can evoke erectile responses when given intracavernously, and it enhances erectionsinduced by cavernous nerve stimulation and apomorphine when given systemically. In vitro YC-1 enhanceselectrically evoked relaxation in rat corpus cavernosum. YC-1 represents an interesting pharmacological prin-ciple, which may be useful in the treatment of erectile dysfunction.

IMPROVED RESULTS WITH INTUSSUSCEPTION PULL-THROUGH END-TO-SIDEMICROSURGICAL VASOEPIDIDYMOSTOMY

Microsurgical vasoepididymostomy is technically challenging, and standard techniques include end-to-side orend-to-end anastomosis. A triangulation end-to-side vasoepididymostomy technique, using placement of 3double-armed sutures in a triangular fashion in the epididymal tubule before its opening, has been described.This procedure results in invagination or intussusception of the epididymal tubule into the vasal lumen.

McCallum et al (page 2284) from New York, New York compare the surgical outcomes of conventional

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end-to-side vasoepididymostomy versus the intussusception vasoepididymostomy in an obstructive azoopermiamodel in rats. Bilateral 2-clip vasectomy was performed on rats, and bilateral intussusception or conventionalvasoepidymostomy was performed 2 weeks later. Patency for the intussusception group was 91.7% versus 54.2%for the conventional group. The sperm granuloma rate was 20.8% for the intussusception group versus 58.4% forthe conventional group. Average operative time was 65.8 minutes for the intussusception versus 67.7 minutes forthe conventional group. The intussusception technique was found to be superior to conventional vasoepidymos-tomy with respect to patency and postoperative sperm granuloma rates.

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