This Month in Investigative Urology

Article Outline

• Freeing the Mesenteric Edge of the Distal Part of Intestinal Conduits Appears Safe
• Replacement of Intestinal Mucosa With Urothelium in Augmented Bladder
• PAK1: A Novel Molecular Marker for Superficial Bladder Cancer Recurrence
• Filling and Emptying are Important for Normal Bladder Development
• Tubular and Interstitial Nephrocalcinosis
• Copyright

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Freeing the Mesenteric Edge of the Distal Part of Intestinal Conduits Appears Safe 

An ileal conduit is performed in approximately half of all urinary diversions. Difficulties in constructing an abdominal stoma in morbidly obese patients can be challenging if the patient has a short mesentery. Excessive traction on the mesentery in an attempt to pass the distal segment of the ileum through the thick abdominal wall may result in ischemia. Abdallah et al (page 1113) from Little Rock, Arkansas, evaluated the safety of freeing the terminal portion of the conduit from its mesentery to facilitate easy passage of the conduit through the abdominal wall. Segments of ileum (10 cm) were isolated to form ileal loops and bowel continuity was established in pigs. A 3 to 4 cm segment of the distal ileal loop was freed from its mesenteric blood supply. The distal segment of the loop was passed through an appropriate defect in the abdominal wall to the skin and an everted stoma was constructed. Mean postoperative time was 30 days (range 29 to 32). No mortality or perioperative complications were recorded. All animals had an uneventful postoperative course until the scheduled specimen collection. At the time of harvesting the stoma remained pink in all animals postoperatively. Gross examination and calibration demonstrated no evidence of narrowing or stenosis. The histological examination demonstrated no ischemic changes. The mucosa of the entire ileal loop was uniform and healthy. The study showed that freeing the mesenteric edge of the ileal loop is safe. This finding has potential applications for the creation of ileal loops or continent cutaneous stomas in morbidly obese patients.

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Replacement of Intestinal Mucosa With Urothelium in Augmented Bladder 

The use of intestinal segment for bladder augmentation may be associated with multiple long-term side effects, many as a result of the continued activity of the absorptive and mucin producing intestinal cells. Removal of the bowel mucosa has been advocated to prevent these problems. Mechanically stripping the bowel mucosa allows the urothelium from the adjacent bladder wall to repopulate the denuded intestinal area, but this may result in fibrosis and a negligible increase in bladder capacity. Baig et al (page 1108) from Toledo, Ohio evaluated the efficacy of intravesical aminolevulinic acid and photodynamic therapy (PDT) for the removal of small intestinal mucosa in augmented bladders in a rat model. Enterocystoplasty was performed in female rats using a patch of terminal ileum. The augmented bladders were treated with intravesical PDT at light doses of 75, 100 and 125 J. After PDT, histology revealed uniform ablation and replacement of the intestinal mucosa with urothelium, and minimal damage to the bladder wall at all light doses. Bladder cystometry revealed no significant change in bladder capacity after photodynamic therapy. In the rat model intravesical aminolevulinic acid and PDT resulted in replacement of intestinal mucosa with urothelium leaving the underlying muscular layer intact. This technology could potentially be a viable option for patients with a preexisting bladder augment.

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PAK1: A Novel Molecular Marker for Superficial Bladder Cancer Recurrence 

It is clinically important to identify bladder cancer with a high risk of intravesical recurrence after transurethral bladder tumor resection. Ito et al (page 1073) from Kyoto, Japan developed molecular markers for the prediction of intravesical recurrence of superficial bladder transitional cell carcinoma (TCC) using oligo-microarray analysis. Gene expression profiles associated with intravesical recurrence were analyzed by oligo-microarray in superficial bladder TCC samples treated with transurethral resection. Microarray identified 25 genes whose expressions were associated with recurrence including Pak1 (P21-activated kinase 1). The expression of Pak1 mRNA was statistically associated with tumor grade and risk of recurrence but not with cancer stage in 86 bladder cancers. Immunohistochemistry and multivariate analysis demonstrated that high expression of Pak1 proteins was an independent factor associated with recurrence. High expression of Pak1 was significantly associated with a high risk of recurrence even in low stage/grade cancers. Transfection with T423E Pak1 into 253J cells progressed cell motility in wound healing assay, whereas transfection with K299R Pak1 reduced motility in EJ cells. These results suggest that the expression of Pak1 is associated with recurrence and might be a useful prognostic marker for superficial bladder TCC.

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Filling and Emptying are Important for Normal Bladder Development 

It is unclear whether filling and emptying are important to bladder development. Wei et al (page 1104) from Philadelphia, Pennsylvania tested this in an experimental preparation. Urinary diversion was performed on 90-day gestation fetal lambs and unoperated fetal lambs were controls. Transmural sections were analyzed for changes in tissue layer thickness and/or composition after 14 days of urinary diversion. Diverted fetal bladders exhibited a 27% and 57% decrease in mucosal and detrusor muscle layer thickness, respectively. In contrast there was a 270% increase in serosal layer thickness in diverted bladders. mRNA levels for collagen1A1, collagen3A1, IGF-1, EGR-1 and the antiapoptotic gene, BCL-2, were increased significantly in the serosal/detrusor layer of the diverted bladders. In the mucosa levels of these same mRNAs remained unchanged except for fibronectin and WT-1, which were significantly decreased and increased, respectively. Total collagen and type I and III collagen protein levels were significantly increased in the diverted bladders. Lack of mechanical loading in diverted bladders leads to an arrest of detrusor smooth muscle growth, and concurrent fibrosis and thickening of the serosal layer. Changes in levels of IGF-1, BCL-2 and EGR-1 likely have regulatory roles that affect the smooth muscle phenotype in the detrusor layer.

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Tubular and Interstitial Nephrocalcinosis 

The accumulation of crystals in the renal calices (nephrolithiasis) and the deposition of crystals in the renal parenchyma (nephrocalcinosis) usually are considered 2 different forms of renal stone disease. Nevertheless, it is possible that nephrolithiasis is preceded by tubular (retention of crystals in the renal tubules) or interstitial (precipitation of crystals in the medullary interstitium) nephrocalcinosis. Unfortunately moderate forms of nephrocalcinosis are not detectable by radiology and biopsies are not taken at early stages of renal stone disease. A yet unproven hypothesis is that nephrolithiasis is a 2-step process requiring tubular nephrocalcinosis followed by the retention and accumulation of crystals in the renal calices. Several investigators have proposed that interstitial nephrocalcinosis can erode into the calices, giving rise to plaques of calcification on the outer wall of the renal pelvis and that crystals floating in the primary urine may grow on these plaques into stones. Although recent evidence suggests that a subset of stones indeed grows firmly attached to such plaques, this is probably not a general mechanism in stone development because there are also stone formers without plaque in the kidneys. To study the occurrence of tubular and interstitial nephrocalcinosis, Kummeling et al (page 1097) from Rotterdam, The Netherlands investigated the presence of crystals in the cortex and medulla from unaffected parts of tumor nephrectomies. To study the effect of tissue handling on the possible loss of crystalline material, various methods of tissue processing were applied to identify crystals in a kidney with tubular nephrocalcinosis due to chronic pyelonephritis. Renal cortical and papillary tissue was obtained from unaffected parts of kidneys removed for oncological indications. The effect of tissue processing on the loss of crystals was studied in a kidney with nephrocalcinosis due to chronic pyelonephritis. Although most snap-frozen sections made from tumor kidneys contained birefringent particles in the renal tubules, this was not considered nephrocalcinosis because the crystals were not attached to the epithelial lining. Interstitial nephrocalcinosis was found in 20% of the tumor kidneys. Calcium deposits were found in the papillary interstitium only and always together with hyaluronan. Formaldehyde fixed sections made from the pyelonephritis kidney contained less renal tubular cell associated birefringent particles than did immediately frozen sections. The particles were composed of calcium oxalate monohydrate. This study suggests that there are 2 distinct forms of nephrocalcinosis, that of tubular nephrocalcinosis, which seems to be reserved for specific conditions such as chronic pyelonephritis, and interstitial nephrocalcinosis. The incidence of tubular calcium oxalate nephrocalcinosis could be underestimated due to the loss of crystals during tissue processing for routine histology. The crystal binding molecule hyaluronan may have a role in both forms of nephrocalcinosis.