Ganesh V. Raj

Ureteral Access Sheath Provides Protection against Elevated Renal Pressures during Routine Flexible Ureteroscopic Stone Manipulation

BACKGROUND AND PURPOSEnNew-generation flexible ureteroscopes allow the management of proximal ureteral and intrarenal pathology with high success rates, including complete removal of ureteral and renal calculi. One problem is that the irrigation pressures generated within the collecting system can be significantly elevated, as evidenced by pyelovenous and pyelolymphatic backflow seen during retrograde pyelography. We sought to determine if the ureteral access sheath (UAS) can offer protection from high intrarenal pressures attained during routine ureteroscopic stone surgery.nnnPATIENTS AND METHODSnFive patients (average age 72.6 years) evaluated in the emergency department for obstructing calculi underwent percutaneous nephrostomy (PCN) tube placement to decompress their collecting systems. The indications for PCN tube placement were obstructive renal failure (N=1), urosepsis (N=2), and obstruction with uncontrolled pain and elevated white blood cell counts (N=2). Flexible ureteroscopy was subsequently performed with and without the aid of the UAS while pressures were measured via the nephrostomy tube connected to a pressure transducer. Pressures were recorded at baseline and in the distal, mid, and proximal ureter and renal pelvis, first without the UAS, and then with the UAS in place.nnnRESULTSnThe average baseline pressure within the collecting system was 13.6 mm Hg. The mean intrarenal pressure with the ureteroscope in the distal ureter without the UAS was 60 mm Hg and with the UAS was 15 mm Hg. With the ureteroscope in the midureter, the pressures were 65.6 and 17.5 mm Hg, respectively; with the ureteroscope in the proximal ureter 79.2 and 24 mm Hg, and with the ureteroscope in the renal pelvis 94.4 and 40.6 mm Hg, respectively. All differences at each location were statistically significant (P<0.008). Compared with baseline, all pressures measured without the UAS were significantly greater, but only pressures recorded in the proximal ureter and renal pelvis after UAS insertion were significantly higher (P<0.03).nnnCONCLUSIONSnThe irrigation pressures transmitted to the renal pelvis and subsequently to the parenchyma are significantly greater during routine URS without the use of the UAS. The access sheath is potentially protective against pyelovenous and pyelolymphatic backflow, with clinical implications for the ureteroscopic management of upper-tract transitional cell carcinoma, struvite stones, or calculi associated with urinary tract infection.

Utilization of polymerase chain reaction technology in the detection of solid tumors

Most cancer detection tests currently performed are based on either antibody assays to a marker protein with altered expression in cancer patients or on imaging studies to identify characteristic lesions. Generally, for a positive result, these detection assays require that a tumor have a significant volume of cancer cells. Advances in diagnostic techniques and technology may allow for cancer detection at earlier stages, when the tumor burden is smaller and potentially more curable. The molecular techniques of polymerase chain reaction (PCR) and reverse transcriptase PCR (RT‐PCR) are highly sensitive methods for detecting a small number of cancer cells. Over the past few years, numerous clinical studies have used PCR techniques to detect physical alterations of genes, such as mutations, deletions, translocations and amplification, the presence of oncogenic viruses, and the expression of genes specific to tissue, cancer, and metastasis. The current status of PCR as a method for detecting marker genes in the management of solid tumors is reviewed.

Outcomes Following Erosions of the Artificial Urinary Sphincter

PURPOSEnArtificial urinary sphincter urethral cuff erosion occurs in up to 5.0% of cases, presenting a complex management problem. We examine our experience with the eroded AUS, relating to preoperative risk factors, operative management and outcomes.nnnMATERIALS AND METHODSnWe reviewed the medical records of 637 patients undergoing bulbar urethral AUS implantation from 1990 to 2003 for demographic and surgical variables.nnnRESULTSnOf the 637 records reviewed, 46 patients underwent 54 explantations of the AUS device for erosions, including 13 who had the primary implant performed at our institution and 33 being referred for management of erosion after implantation elsewhere. Our institution erosion rate was 2.2%. Mean followup after AUS reimplant following erosion was 27.8 months (range 1 to 180). Comorbidities were more prevalent in patients with erosions included hypertension (p = 0.006), coronary artery disease (p = 0.03), prior radiation therapy (p = 0.006) and prior AUS revisions (p = 0.0001). A majority of patients had persistent mild incontinence (0 to 1 pad daily in 29 or 56.8%), moderate (1 to 3 pads daily in 9 or 17.4%) and severe (more than 3 pads daily in 6 or 11.8%) incontinence after secondary AUS implantation. Patients who underwent reimplantation after AUS cuff erosions have a significantly higher rate of second erosions (in 16, 34.8%) within an average of 6.7 months (range 3 to 24), including our own 11.8% institutional rate (in 4).nnnCONCLUSIONSnOur study suggests that patients with comorbidities including hypertension, coronary artery disease, prior radiation therapy and prior AUS revisions are more likely to have erosions of their AUS. Nevertheless, continence can still be salvaged using various strategies which optimize use of the remaining healthy urethral tissue.

Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy

Despite the ability of radical prostatectomy to eradicate prostate carcinoma, biochemical evidence of recurrent prostate carcinoma may be seen in approximately 40% of patients 15 years after they undergo surgery. Localization of recurrent disease after radical prostatectomy is difficult and may greatly influence subsequent clinical management. The authors examined the utility of indium 111 (111In)‐capromab pendetide immunoscintigraphy to detect recurrent prostate carcinoma radiographically in men with early biochemical evidence of failure (serum prostate specific antigen [PSA] ≤ 4.0 ng/mL) and assessed the minimum serum PSA level necessary for imaging recurrent disease.

Management of small renal tumors: an overview

The incidental finding of a small renal mass poses a therapeutic dilemma. The traditional treatment of clinically important masses has been radical nephrectomy. Recently, nephron-sparing surgery has emerged as a viable alternative; and experimental minimally invasive percutaneous tissue ablation techniques, including cryotherapy and radiofrequency ablation, are being evaluated. In this review, we discuss the dilemma posed by frequent renal imaging and the increased proportion of incidental tumors being detected, the limitations of needle biopsies for histologic diagnosis, nephron-conserving and minimally invasive surgery, and the possible merits of radiofrequency ablation and cryotherapy. We envision a defined role for minimally invasive percutaneous or extracorporeal ablation of small renal tumors.

Laser Doppler Flowmetric Determination of Ureteral Blood Flow after Ureteral Access Sheath Placement

BACKGROUND AND PURPOSEnThe ureteral access sheath has positively impacted ureteroscopy by decreasing operative times and increasing success rates. However, as previous studies have suggested that large-caliber endoscopes may cause ureteral ischemia, concern has been raised about the impact of access sheath insertion on ureteral blood flow. We sought to determine whether the access sheath compromises ureteral blood supply and, if so, causes ischemic damage to the ureter during ureteroscopic procedures.nnnMATERIALS AND METHODSnUsing a swine animal model, ureteral blood flow was measured with a laser Doppler flowmeter. Eleven ureteral units were randomized into four study groups: those dilated with 10F-12F, 12F-14F, and 14F-16F access sheaths (N = 3 per group) and an undilated control group (N = 2). Blood flow measurements were obtained from the proximal ureter via laser Doppler flowmetry for 70 minutes at 5-minute intervals. Hemodynamic variability was controlled for through intraoperative heart rate and oxygen saturation monitoring, as well as a second Doppler probe that was placed on the animals skin, from which readings were also taken every 5 minutes. Results were correlated with histopathologic findings.nnnRESULTSnThe control group demonstrated little ureteral blood flow variability over the course of 70 minutes. The study groups that were dilated with sheaths, however, all showed a decrease in ureteral blood flow after access sheath insertion, with the flow in animals dilated with 12F-14F and 14F-16F sheaths dropping below 50% of baseline. This initial drop in blood flow was followed by a gradual increase from nadir toward baseline values over the course of the study. On average, the 14F-16F group reached nadir more quickly and took longer to restore its ureteral blood flow. All animals remained hemodynamically stable throughout the study, showing only minimal variability in heart rate, oxygen saturation, and skin blood flow over the 70-minute experiment. Histologically, there was no evidence of ischemic damage in any of the study groups at 72 hours.nnnCONCLUSIONSnIn this animal model, the access sheath does cause a transient decrease in ureteral blood flow. Nonetheless, compensatory mechanisms of the ureteral wall restore blood flow to near-baseline rates and preserve urothelial integrity, suggesting that use of the ureteral access sheath remains a safe adjunct to flexible ureteroscopy. Because the chronic effects of the access sheath have yet to be elucidated, care must be taken in selecting an appropriate-size sheath for each individual case. Preventive measures may be available to help avoid sheath-related ureteral injury in those patients identified as high risk.

Metabolic abnormalities associated with renal calculi in patients with Horseshoe kidneys

BACKGROUND AND PURPOSEnHorseshoe kidneys are a complex anatomic variant of fused kidneys, with a 20% reported incidence of associated calculi. Anatomic causes such as high insertion of the ureter on the renal pelvis and obstruction of the ureteropelvic junction are thought to contribute to stone formation via impaired drainage, with urinary stasis, and an increased incidence of infection. In this multi-institutional study, we evaluated whether metabolic factors contributed to stone development in patients with horseshoe kidneys.nnnPATIENTS AND METHODSnA retrospective review of 37 patients with horseshoe kidneys was performed to determine if these patients had metabolic derangements that might have contributed to calculus formation. Stone compositions as well as 24-hour urine collections were examined. Specific data points of interest were total urine volume; urine pH; urine concentrations of calcium, sodium, uric acid, oxalate, and citrate; and number of abnormalities per patient per 24-hour urine collection. These data were compared with those of a group of 13 patients with stones in caliceal diverticula as well as 24 age-, race-, and sex-matched controls with stones in anatomically normal kidneys.nnnRESULTSnEleven (9 men and 2 women) of the 37 patients (30%) with renal calculi in horseshoe kidneys had complete metabolic evaluations available for review. All patients were noted to have at least one abnormality, with an average of 2.68 abnormalities per 24-hour urine collection (range 1-4). One patient had primary hyperparathyroidism and underwent a parathyroidectomy. Low urine volumes were noted in eight patients on at least one of the two specimens (range 350-1640 mL/day). Hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia were noted in seven, three, six, and six patients, respectively. No patients were found to have gouty diathesis or developed cystine stones. Comparative metabolic analyses of patients with renal calculi in caliceal diverticula or normal kidneys revealed a distinct profile in patients with horseshoe kidneys, with a higher incidence of hypocitraturia.nnnCONCLUSIONSnAll patients with renal calculi in horseshoe kidneys were noted to have metabolic abnormalities predisposing to stone formation. In this initial series of 11 patients, hypovolemia, hypercalcuria and hypocitraturia were most common metabolic defects. These findings suggest that metabolic derangements play a role in stone formation in patients with a horseshoe kidney. Patients with calculi in anatomically abnormal kidneys should be considered for a metabolic evaluation to identify their stone-forming risk factors in order to initiate preventative selective medical therapy and reduce the risk of recurrent calculus formation.

GUANOSINE PHOSPHATE BINDING PROTEIN COUPLED RECEPTORS IN PROSTATE CANCER: A REVIEW

PURPOSEnAndrogens are the primary growth promoters of the prostate gland and yet prostate tumors progress despite androgen ablation. This progression suggests a role for additional cellular factors in the progression to androgen independent disease. We examined the role of a family of extracellular signal regulators, namely the guanosine phosphate binding (G) protein coupled receptor (GPCR) family, in prostate cancer.nnnMATERIALS AND METHODSnA comprehensive review of the literature was performed on GPCRs and prostate cancer, and supplemented with published and unpublished observations made at our laboratory. Emphasis was placed on the mechanistic aspects of mitogenic signaling pathways involved to identify potential targets for therapy.nnnRESULTSnExpression of some GPCRs and GPCR ligands is elevated in prostate cancer cells and adjacent prostatic stromal tissue. In vitro studies demonstrate that activation of GPCRs confers a distinct growth and survival advantage on prostate cancer cells, including enhanced proliferation and decreased programmed cell death (apoptosis). Specifically stimulation of GPCRs for lysophosphatidic acid and bradykinin induces proliferation of androgen independent prostate cancer cells via the activation of the extracellular signal regulated kinase (ERK) pathway. Induction of ERK by the bradykinin and lysophosphatidic acid in prostate cells proceeds via distinct pathways and involves Galphaq and Gbetagamma subunits, respectively. The Gbetagamma dependent activation of ERK requires tyrosine kinases, including epidermal growth factor receptor and c-Src. Furthermore, stimulation with LPA enhances the survival of prostate cancer cells via activation of the inducible transcription factor nuclear factor-kappaB.nnnCONCLUSIONSnGPCR stimulation induces proliferation and prevents apoptosis of hormone independent prostate cancer cells, indicating their important role in the progression of prostate cancer. While further confirmatory studies are required to verify the role of GPCRs in disease progression, the therapeutic implications of these studies may enhance the armamentarium in the fight against prostate cancer.

THE INCIDENCE OF NEPHROLITHIASIS IN PATIENTS WITH SPINAL NEURAL TUBE DEFECTS

PURPOSEnBladder stones are common in patients with spinal neural tube defects but there are little data on the incidence of renal calculi in this population. We examined the incidence, nature and risk factors of nephrolithiasis in our clinic population of patients with neural tube defects.nnnMATERIALS AND METHODSnWe retrospectively reviewed the charts and radiological studies of 327 patients followed at our neural tube defects clinic with routine radiological imaging of the urinary tract. Additional confirmatory studies were performed when stones were noted.nnnRESULTSnRenal calculi were identified in 20 patients with neural tube defects (6.1%). The incidence of nephrolithiasis increased with age. Renal stones were noted in 19 patients (10.7%) 12 years old or older. Management of the stones in these patients resulted in overall 53% stone-free and 87% recurrence rates after intervention. Major risk factors for new and/or recurrent renal stone formation were bacteriuria in 95% of the cases, lower urinary tract reconstruction in 80%, pelvicalicectasis in 70%, vesicoureteral reflux in 65%, a thoracic level spinal defect in 60% and renal scarring in 55%.nnnCONCLUSIONSnThese data suggest that there is a higher incidence of nephrolithiasis in patients with neural tube defects than in the general population and the risk of stone recurrence is also elevated. Most patients with stones had undergone lower urinary tract reconstruction. Other risk factors were bacteriuria, pelvicalicectasis, vesicoureteral reflux and a thoracic level neural tube defect.

Liposarcoma presenting as an intraluminal ureteral mass.

An 86-year-old woman with a previous excision of a large retroperitoneal low-grade liposarcoma presented with a 4-month history of persistent left flank discomfort. Workup revealed left hydronephrosis secondary to obstruction, which was caused by a recurrent liposarcoma in the intraluminal ureter. She underwent a left nephroureterectomy for symptomatic palliation. Pathologic study revealed high-grade liposarcoma. Despite negative surgical margins, the tumor rapidly recurred, leading to death only 4 months after surgery. This case highlights the aggressive nature of liposarcoma.