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Introduction: The litigious environment encompassing the medical-legal domain is an increasing concern for surgical fields, with urology being no exception. The objective of our study was to systematically review, evaluate, and summarize the factors associated with oncologic nephrectomy litigation to determine possible factors contributing to verdicts or settlements. Materials and Methods: Publicly available verdict reports were retrieved using the Westlaw ® legal database (Reuters). Cases were identified using the search term "nephrectomy" with dates ranging from January 1, 1990 to July 1, 2019. Each case was evaluated by two independent reviewers for defendant specialty, alleged breach in treatment, resulting complications, verdict outcomes, and indemnity payment. Complications were determined to be preoperative, perioperative, and postoperative. Data were analyzed using SPSS software to produce the descriptive statistics. Results: After accounting for duplicates and irrelevant cases, a total of 103 cases were analyzed with more than three-fourths being radical nephrectomies (78%). The most common claim was preoperative negligence (48%); however, negligence in perioperative care received the highest average monetary payment of $5,493,151. Forty-one percent of cases were perioperative with the majority being attributed to vascular injury (46%). The type of perioperative negligence claims and its average payment were found to be statistically significant ( p  = 0.042). Overall, 57% of cases denied the plaintiff's claims, whereas 28% were awarded. Conclusions: Our data show that although the highest number of cases were caused by preoperative negligence, perioperative negligence accounts for the highest settlement awards. This review provides insights into stages of management in the surgical management of renal cell cancer patients that may be subject to litigation.

Background: Although single-port donor nephrectomy offers improved cosmetic outcomes, technical challenges have limited its application to selected centers. Our center has performed over 400 single-port donor nephrectomies. The da Vinci single-site robotic platform was utilized in an effort to overcome the steric, visualization, ergonomic, and other technical limitations associated with the single-port approach., Materials and Methods: Food and Drug Administration device exemption was obtained. Selection criteria for kidney donation included body mass index <35, left kidney donors, and ≤2 renal arteries. After colonic mobilization using standard single-port techniques, the robotic approach was utilized for ureteral complex and hilar dissection., Results: Three cases were performed using the robotic single-site platform. Average total operative time was 262 ± 42 min including 82 ± 16 min of robotic use. Docking time took 20 ± 10 min. Blood loss averaged 77 ± 64 mL. No intraoperative complications occurred, and all procedures were completed with our standard laparoscopic single-port approach., Conclusions: This is the first clinical experience of robotic-assisted donor nephrectomy utilizing the da Vinci single-site platform. Our experience supported the safety of this approach but found that the technology added cost and complexity without tangible benefit. Development of articulating instruments, energy, and stapling devices will be necessary for increased application of robotic single-site surgery for donor nephrectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Minimally invasive techniques have expanded the donor pool for living kidney donation. We changed our approach to single-port donor nephrectomy in 2009 and have compared outcomes with traditional multiple-port laparoscopic donor nephrectomy., Background: The development of minimally invasive surgical techniques to procure kidneys from living donors has allowed expansion of living donor renal transplantation to account for one third of all renal transplants. Recent technical advancement allows for the entire surgical procedure to be done through a single incision contained within the umbilicus., Methods: We compared outcomes from 135 single-port donor nephrectomies with an immediately preceding cohort of 100 multiple-port laparoscopic donor nephrectomies. Survey data were collected from both groups to compare outcomes. Additional comparisons were made to total center experience with 1300 laparoscopic donor nephrectomies., Results: A total of 135 patients completed successful single-port donor nephrectomy without major complication or open conversion. Another 16 patients required additional port placement because of excessive intra-abdominal fat or limited abdominal domain. Compared with multiple-port donor nephrectomy, single-port patients had similar operative times to cross clamp (2.8 vs 2.6 hours; P = 0.11) that normalized after a learning curve of approximately 50 cases. Recipient creatinine levels were similar at 1 week and 1 month posttransplant. Although 36-Item Short Form Health Surveys demonstrated no significant differences, additional survey data revealed that single-port patients were more satisfied with cosmetic outcomes (P < 0.01) and the overall donation process (P = 0.01). Single-port approach had similar outcomes compared with all previous laparoscopic donor nephrectomies., Conclusions: Single-port donor nephrectomy can be integrated as a standardized approach for renal donation without additional donor risk, and with benefits of improved patient satisfaction with cosmetic and overall outcomes. Although the primary benefit is cosmetic, (a single incision predominantly contained within the umbilicus) outcomes justify application for kidney donors in experienced centers and may motivate additional living kidney donation.

Adenomatoid tumor of the male genitourinary tract is a rare benign neoplasm thought to be of mesothelial origin. In exceptional cases, these lesions may involve the testicular parenchyma, of which there are only 9 published cases in the literature. The authors describe a rare case of a testicular tumor in a 41-year-old male with normal tumor markers. Histopathology and immunohistochemical studies revealed an adenomatoid tumor with intratesticular growth. No involvement of the epididymis or testicular membranes was identified. The morphological clues leading to the correct diagnosis of adenomatoid tumor and the possible histogenesis and differential diagnosis are discussed.

Background: Dialysis patients and transplant recipients, especially those with acquired cystic kidney disease, are at increased risk for renal cell carcinoma (RCC). We report our experience in 15 posttransplant patients who underwent nephrectomy for renal masses., Methods: Institutional review board-exempt retrospective chart review was performed on 15 transplant recipients who subsequently underwent native nephrectomy for masses., Results: A total of 22 renal units were removed from 15 patients, with 18 kidneys removed laparoscopically and 4 via an open approach. Of those 22 kidneys, 17 units (77%) from 13 patients contained RCC. One kidney had two cancers, for a total of 18 cancers. The distribution of RCC is as follows: 11 papillary, 4 clear cell, and 3 chromophobe. Ten patients were stage T1N0M0, two patients were stage T2N0M0, and one was stage T3N0M0. No patients had immunosuppression withheld. The average length of stay for laparoscopic nephrectomy was 95 hr, with a median length of stay of 61 hr (range 33-360 hr). Surgical complications (7%) included a delayed extraction site hernia. There were no episodes of rejection, dialysis, or injury to the kidney. One patient developed pulmonary metastasis. Average follow-up and metastasis-free survival was 60.6 and 58.4 months, respectively., Conclusions: Renal transplant recipients with suspicious masses or cancer or both can safely undergo native nephrectomy without jeopardizing their grafts by stopping immunosuppression. Immunosuppression does not seem to promote metastasis or recurrence, although longer follow-up is required. As in patients on hemodialysis, papillary RCC is more common than clear cell carcinoma.

Background and Purpose: Renal fossa recurrence of renal-cell carcinoma (RCC) after radical nephrectomy historically necessitates open surgical resection. Cryoablation provides a minimally invasive alternative to open resection for local recurrence. We describe our experience with percutaneous cryoablation in three patients who were experiencing fossa recurrence., Patients and Methods: We retrospectively reviewed medical records of three patients with renal fossa recurrence of RCC who were treated with percutaneous cryoablation., Results: Percutaneous cryoablation was well tolerated; no complications were noted, and patients were discharged within 23 hours. One patient needed an additional cryoablation procedure, and one patient underwent subsequent open extirpation. Metastatic disease developed in one patient, while the other two patients remain negative for disease by axial imaging and percutaneous biopsy. All patients are alive at 43 months (range 22-54 months)., Conclusions: Percutaneous cryoablation, a minimally invasive intervention, has low morbidity and may be offered as an alternative to extirpation, although long-term oncologic data are lacking.

Objectives: To assess transplantation of high-risk kidneys with incidental renal masses (found occasionally during the routine evaluation of a living kidney donor) into recipients with limited life-expectancy on haemodialysis, as this offers a potential solution to the current organ deficit., Patients and Methods: We detected five small (<2.3 cm), incidental, enhancing renal masses during donor evaluation. All patients had a standard metastatic evaluation. After laparoscopic donor nephrectomy a back-table partial nephrectomy was performed and frozen-section analysis was used to confirm both the diagnosis and negative surgical margins before transplantation., Results: Renal cell carcinoma was found in three of the five masses (one each cystic, clear cell and papillary; Fuhrman grades II, II and III, respectively) and the other two patients had angiomyolipoma. There were no long-term complications in the transplanted kidneys. One patient developed delayed acute humoral rejection after transplantation and was treated appropriately. Both donor and recipient were followed with periodic imaging. At a median (range) last follow-up of 15 (1-41) months, four patients were alive and one had died from complications after a fall. The cancer-specific survival was 100%. There was no evidence of local recurrence in any patient at the last follow-up., Conclusion: Live donor kidneys with incidental small renal masses might be acceptable for transplantation in high-risk recipients after careful back-table partial nephrectomy.

Objective: Renal artery aneurysms are being discovered more frequently due to increased use of non-invasive imaging. Complex renal artery aneurysms involving multiple secondary or tertiary branches are not amenable to in vivo or endovascular treatment and often require ex vivo repair with autotransplantation. In order to minimize incisional morbidity and hasten recovery, we developed a technique of laparoscopic nephrectomy combined with backbench ex vivo repair, followed by autotransplantation through a small laparoscopic extraction incision. This study describes our initial experience with this combined technique in patients that were not candidates for endovascular techniques or in vivo arterial reconstruction., Methods: Seven patients with complex renal artery aneurysms underwent laparoscopic nephrectomy and ex vivo repair with multiple saphenous vein grafts and autotransplantation through the small laparoscopic extraction incision. The aneurysms ranged from 2.5 to 5.0 cm. In all cases, the aneurysm was resected ex vivo, leaving multiple branch arteries that were extended with saphenous vein grafts. Arterial inflow was then re-established with sequential saphenous vein anastomoses to the external iliac artery. Ureteral reconstruction was performed via standard Lich ureteroneocystostomy. Patients were followed postoperatively for two to eight years., Results: Laparoscopic nephrectomy with ex vivo repair of complex aneurysms was successfully employed in seven patients with renal aneurysms that were not amenable to endovascular or in vivo repair. There were no incisional morbidities and all patients had significant improvements in symptoms post-operatively. Renal function remained unchanged and there were no ureteral complications following surgery. All patients had postoperative ultrasound imaging done at two years which demonstrated patency of the anastomoses. The mean hospital stay was four days (range, two to seven days)., Conclusion: Repair of complex renal artery aneurysms involving distal branch arteries remains a challenge. This new technique combines the advantages of minimally invasive surgery with the effectiveness of ex vivo aneurysm repair.

We have previously reported that renal allografts procured by the laparoscopic live donor nephrectomy (lapNx) demonstrate worse early renal outcomes but noninferior 1-year renal function as compared to those procured by the standard open nephrectomy (openNx). We undertook this study to examine whether the apparent early dysfunction will impair long-term renal allograft survival. We retrospectively updated the status of the first 132 consecutive adult left lapNx recipients at our center and the preceding 99 adult openNx recipients. With a mean follow-up of 5.8+/-2.0 years in lapNx and 8.7+/-3.3 years in openNx, we found that death-censored renal allograft survival was identical on univariate and multivariate analysis. Patient survival was worse (log rank P-value=0.048) in lapNx, but this finding did not persist in multivariate analysis. Combined graft-patient survival as well as 1-year mean serum creatinine levels were similar on univariate and multivariate analyses. We conclude that, despite having suffered early renal dysfunction, the lapNx cohort of renal allograft recipients enjoys similar long-term renal allograft survival as compared to openNx.

The effect of both donor renal mass and gender on renal function, in both gender recipients, was examined. Qualifying consecutive living-donor renal transplants (n = 730) were stratified into 4 donor-recipient groups: female-female (n = 177), male-female (n = 151), female-male (n = 240), male-male (n = 162). Groups were equivalent in age, race, body mass index (BMI), match, ischemia time, operative time, and estimated glomerular filtration rate (eGFR). Female recipients had lower serum creatinine (Cr(s)). Male recipients had higher Cr(s) wherever they received a female allograft. Male recipients of male kidneys had a higher eGFR than all other groups for 3 years. Renal function of the recipient correlated with the renal mass of the donor within each group. Male and female kidneys functioned equivalently in the female-recipient environment. Large nephron-mass male donor kidneys function more poorly in female recipients. The male kidney loses 15-20 ml/min eGFR in the female host. The diminished graft function may be related to androgen deprivation. Female and male donor kidneys function equivalently in the male recipient if adjusted for renal mass transplanted. Female kidneys improve eGFR by 7-10 ml/min by being transplanted into a male environment. Donor renal mass and gender affect recipient graft function Expectations of ultimate recipient renal function should take into account both the gender and mass disparity of the donor-recipient pair.

Background and Purpose: Laparoscopic renal cryoablation is an emerging minimally invasive management option for T(1) renal lesions. In an analysis of patients treated with laparoscopic cryoablation for renal lesions, our objective was to compare the treatment outcomes in patients with exophytic/partially exophytic and endophytic (peripheral but completely intrarenal) lesions., Patients and Methods: We retrospectively reviewed medical records of 32 consecutive patients with anterior renal lesions who were treated with laparoscopic renal cryoablation between 2003 and 2005. Biopsy samples were obtained from the majority of lesions intraoperatively. The lesions were managed with 17 gauge needles and two freeze/thaw cycles. Follow-up was performed with CT scans at 3, 6, and 12 months, and then yearly. Treatment failures were defined as continued enhancement on CT or growth of the lesion. Statistical analysis was performed using t-test, correlative, and multiple regression analysis., Results: A total of 35 lesions in 32 patients were identified. Median lesion size was 1.9 cm. Median age was 67 years, with most patients having significant comorbidities. The median preoperative and postoperative creatinine level was 1.3 and 1.5 mg/dL (P = 0.38). Of the biopsy samples from 27 of 35 lesions, 18 showed renal cell carcinoma, 5 were found to be benign, and findings from 4 were inconclusive. Three lesions were completely endophytic. The median follow-up was 18 months, with treatment failures noted in 2 of 35 lesions (6%), both of which were endophytic (P < 0.0001). Multivariate analysis revealed that only the endophytic status of a lesion was a predictor of failure (P < 0.05). These were lesions that relied entirely on intraoperative ultrasonography for targeting, which suggests that failure was a technical error., Conclusions: Experience with renal cryoablation is still evolving. Our series further defines the role of laparoscopic renal cryoablation and its limitations in managing peripheral endophytic tumors. Completely endophytic lesions have a significantly higher risk of treatment failure. Reliance solely on intraoperative ultrasonography with no visual cues is a risk factor for treatment failure.

The kidney is a common location for micrometastases in patients with malignant melanomas. These lesions are usually small, multiple, asymptomatic, and bilateral, and associated with a known primary lesion. This is an unusual case of a 38-year-old woman, with no history of melanoma, presenting with an asymptomatic solitary renal mass and two lung masses. She was doing well 3 months after laparoscopic radical nephrectomy and one course of interleukin-2 therapy.

Purpose: Renal cell carcinoma with inferior vena caval thrombus remains a complex challenge for the urologist. Aggressive surgery to remove all tumor can result in long-term survival. Liver transplant techniques, assistance from cardiac surgeons and bypass techniques can yield optimal vascular control but there is still a blind element inside the inferior vena cava when the thrombus is evacuated. We present data on a technique using a flexible cystoscope to evaluate the lumen of the intrahepatic and suprahepatic inferior vena cava after nephrectomy and tumor thrombectomy., Materials and Methods: Seven patients underwent radical nephrectomy and tumor thrombectomy for renal cell carcinoma with inferior vena caval thrombus. During surgery and after removal of the tumor thrombus a flexible cystoscope was inserted into the venacavotomy for direct inspection of the inferior vena caval lumen. Any residual tumor was manipulated out of the lumen and removed. Patient records were reviewed for data on the time of this procedure, estimated blood loss, residual tumor, postoperative complications and survival., Results: Venacavoscopy required an average additional 5.6 minutes and residual tumor was found in 3 of 7 patients. Average estimated blood loss was 1,170 cc and it was not affected by venacavoscopy. One patient experienced acalculous cholecystitis, possibly as a result of this procedure. Mean followup was 17.6 months with 5 of 7 patients alive., Conclusions: Venacavoscopy is a safe, reliable method of intraoperative inspection of the inferior vena cava that uses equipment and techniques familiar to every urologist. This can help prevent incomplete thrombectomy and disastrous pulmonary embolus.

Diabetic cystopathy is one of the common complications of diabetes and current therapy is limited. In the present study, the effects of gene therapy, using replication-defective herpes simplex virus type 1 (HSV-1) vectors to deliver and express the nerve growth factor (NGF) gene (HSV-NGF) on tissue NGF levels and bladder function, were evaluated in streptozotocin (STZ)-induced diabetic rats. Diabetic rats exhibited a significant decrease in NGF levels in the bladder and lumbosacral dorsal root ganglia (DRG) detected by enzyme-linked immunosorbent assay and displayed marked bladder dysfunction 12 weeks after STZ injection. In contrast, rats with bladder wall injection of the NGF expression vector 8 weeks after STZ treatment exhibited a significant increase of NGF levels in the bladder and L6 DRG 4 weeks after HSV-NGF injection. Along with the restoration of tissue NGF expression, in metabolic cage studies and cystometry, HSV-NGF-injected rats also showed significantly reduced bladder capacity and postvoid residual volume than diabetic rats injected with the control vector (HSV-lacZ), indicating that voiding function was improved after HSV vector-mediated NGF gene delivery. Thus, HSV vector-mediated NGF gene therapy may prove useful to restore decreased NGF expression in the bladder and bladder afferent pathways, thereby improving hypoactive bladder function in diabetes.

Objectives: To report our results after antegrade endoscopic treatment of ureteral stenosis with balloon dilation with or without holmium laser endoureterotomy. Ureteral stenosis is the most common long-term urologic complication of renal transplantation., Methods: From July 2000 to October 2002, 9 renal transplant patients with ureteral obstruction diagnosed by an increase in serum creatinine and radiologic evidence presented for endoscopic treatment. All patients were treated with nephrostomy tube drainage followed by antegrade flexible nephroureteroscopy and balloon dilation of the stricture. Three patients required holmium laser endoureterotomy during the same procedure because of fluoroscopic and endoscopic evidence of persistent stricture. All patients were treated with ureteral stents and nephrostomy tubes postoperatively. The median follow-up was 24 months (range 6 to 32)., Results: The site of stenosis was at the ureterovesical anastomosis in all patients, and the mean stricture length was 0.28 cm. Two patients had previously undergone ureteroneocystostomy for prior ureteral stenosis. Six patients (66%) required only balloon dilation, and 3 patients (33%) also required holmium laser endoureterotomy. The median ureteral stent and nephrostomy tube duration was 40 and 62 days, respectively. The mean serum creatinine level was 2.3 mg/dL at presentation and 1.7 mg/dL at the last follow-up visit. After a median follow-up of 24 months, the ureteral patency and graft function rates were both 100%. No perioperative complications occurred., Conclusions: Balloon dilation with or without holmium laser endoureterotomy was successful and safe in this group of renal transplant patients with short ureterovesical anastomotic strictures.

Purpose: We evaluated pain, convalescence and health related quality of life in patients undergoing laparoscopic and open mini-incision donor nephrectomy., Materials and Methods: We compared the records of consecutive patients who underwent laparoscopic and mini-incision open donor nephrectomy from our donor nephrectomy data base in retrospective fashion using 2 questionnaires. The first questionnaire evaluated postoperative pain, return to functioning time and satisfaction. The second questionnaire was the RAND 36-Item Health Survey, version 2, a standardized and validated health survey quality of life assessment tool. Mean patient sex, age and followup were similar for the 2 groups. All data were analyzed using the 2-tailed t test for independent variables with commercially available statistical analysis software., Results: Pain in the laparoscopic group was significantly less than in the mini-incision group at all followup time points (p <0.05). Statistically significant differences demonstrated that laparoscopy led to more rapid recovery time in certain categories, including walking, discontinuation of prescribed oral pain relievers, return to driving, and resumption of normal work and home daily activities. More subjective questions in the survey showed high levels of acceptance for the 2 procedures. Using the RAND 36-Item Health Survey, version 2 health related quality of life was significantly higher in the laparoscopy group in 3 domains that measure bodily pain, physical functioning and emotional role functioning. However, each group scored at or above age matched American averages in all domains., Conclusions: The laparoscopy group had significantly less postoperative pain and required less time to return to normal functional activities than the mini-incision group. In addition, the laparoscopic group showed significantly higher quality of life scores than the mini-incision group in 3 domains.

Surgical extirpation remains the most effective therapy for renal cell carcinoma. The surgical management of renal masses has evolved away from radical nephrectomy and now includes nephron-sparing surgery for small tumors. Nephron-sparing surgery has similar cure rates and does not appear to compromise cancer control. As the detection of small renal masses by widespread abdominal imaging continues to increase, so will the demand for minimally invasive nephron-sparing procedures. Despite progress in surgical techniques, laparoscopic partial nephrectomy remains a technically challenging procedure. In this review, we discuss the challenges and recent advances in laparoscopic partial nephrectomy and other minimally invasive approaches to renal masses.

PURPOSE It has been proposed that a deficiency in the axonal transport of nerve growth factor (NGF) may have an important role in inducing diabetic neuropathy, which contributes to diabetic cystopathy. Therefore, in streptozotocin (Sigma Chemical Co., St. Louis, Missouri) induced diabetic rats we investigated the relationship of bladder function with NGF levels in the bladder and lumbosacral dorsal root ganglia, which contain afferent neurons innervating the bladder. MATERIALS AND METHODS At 6 and 12 weeks after the induction of diabetes with streptozotocin (65 mg./kg. intraperitoneally) the effects of diabetes on Adelta afferent fiber dependent, conscious voiding were evaluated by metabolic cage measurements and awake cystometry. The effects of diabetes on C-fiber mediated bladder nociceptive responses were also investigated by cystometry with intravesical instillation of 0.25% acetic acid in the rats under urethane anesthesia. NGF levels in the bladder and L6 to S1 dorsal root ganglia were measured by enzyme-linked immunosorbent assay 3, 6, 9 and 12 weeks after streptozotocin injection. RESULTS In diabetic rats NGF levels in the bladder and L6 to S1 dorsal root ganglia were significantly decreased 12 weeks after streptozotocin injection (p <0.01). In cystometry and metabolic cage studies bladder capacity and post-void residual volume were significantly increased 12 weeks after streptozotocin injection (p <0.01). Bladder nociceptive responses revealed by a reduction in inter-contraction intervals after acetic acid infusion were significantly decreased in a time dependent manner 12 weeks after streptozotocin injection.CONCLUSIONS Rats with streptozotocin induced diabetes mellitus showed a significant time dependent decrease in NGF levels in the bladder and L6 to S1 dorsal root ganglia that was associated with voiding dysfunction attributable to defects in Adelta and C-fiber bladder afferents. Therefore, reduced production of NGF in the bladder and/or impaired transport of NGF to L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, may be an important mechanism inducing diabetic cystopathy.

Purpose: Diabetic cystopathy resulting from sensory neuropathy may potentially be treated by direct gene therapy. It has been suggested that nerve growth factor (NGF) has an ameliorative effect in preventing the death in diabetes of afferent dorsal root ganglion neurons, which control bladder function. We investigated NGF gene transfer to the bladder and bladder afferent pathways for treating diabetic cystopathy. We used replication competent and replication defective herpes simplex virus type 1 (HSV-1) vectors that express a functionally active form of the beta-subunit of mouse NGF (beta-NGF) to examine the level and duration of therapeutic gene expression after administration of the vectors., Materials and Methods: NGF expression during acute (3 days) and latent (21 days) infections was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical testing after the injection of 1 x 106 to 1 x 108 pfu HSV-NGF expression vectors into the bladder wall of adult rats., Results: HSV vectors with the strong human cytomegalovirus immediate early promoter used to drive beta-NGF gene expression exhibited increased NGF 3 days after infection in the bladder and L6 to S1 dorsal root ganglia, where bladder afferent neurons are located. ELISA analysis revealed that NGF in the bladder tissue and dorsal root ganglia was increased 7 to 9 and 2 to 4-fold, respectively, over the control vector. Increased NGF expression in L6 to S1 dorsal root ganglia neurons was also detected by immunohistochemical staining with antiNGF antibodies. Extended NGF expression was detected by ELISA 21 days after injection. Replication defective vectors containing HSV-1 latency promoter (LAP-2) driving NGF expressed NGF in the bladder and dorsal root ganglia 21 days after bladder injection. ELISA analysis confirmed an approximate 2 to 3-fold increase of NGF expression in the bladder and L6 to S1 dorsal root ganglia., Conclusions: The NGF gene may be transferred and expressed in the bladder and bladder afferent pathways using HSV vectors. To our knowledge our study represents the first demonstration of the effectiveness of gene therapy for altering neurotrophic expression in visceral sensory neurons. This technique of gene transfer may be useful for treating certain types of neurogenic bladder dysfunction, such as diabetic cystopathy, in which decreased NGF transport may be a causative factor.

Purpose: Botulinum toxin injection into the external urinary sphincter in spinal cord injured men with detrusor-sphincter dyssynergia has been reported. We expand the clinical use of botulinum toxin for a variety of bladder outlet obstructions and to decrease outlet resistance in patients with acontractile detrusor but who wish to void by the Valsalva maneuver., Materials and Methods: Prospective treatment was performed for voiding dysfunction in 8 men and 13 women 34 to 74 years old. The reasons for voiding dysfunction included neurogenic detrusor-sphincter dyssynergia in 12 cases, pelvic floor spasticity in 8 and acontractile detrusor in 1 patient with multiple sclerosis who wished to void by the Valsalva maneuver. Using a rigid cystoscope and a collagen injection needle, a total of 80 to 100 units of botulinum A toxin (Botox) were injected into the external sphincter at the 3, 6, 9 and 12 o'clock positions., Results: Preoperatively 19 of 21 patients were on indwelling or intermittent catheterization. After botulinum A injection all but 1 patient were able to void without catheterization. No acute complications, such as general paralysis or respiratory depression, occurred and none of the patients had dribbling or stress urinary incontinence. Postoperative post-void residual decreased by 71% and voiding pressures decreased on average 38%. Of the 21 patients 14 (67%) reported significant subjective improvement in voiding. Followup ranges from 3 to 16 months, with a maximum of 3 botulinum A injections in some patients., Conclusions: Urethral sphincter botulinum injection should be considered for complex voiding dysfunction. Encouraging improvement without complications were seen in most of our patients. We have expanded the use of botulinum toxin to treat pelvic floor spasticity and also women.

Objectives: Transurethral resection (TURP) or incision of the prostate is generally not effective for treating bladder outlet obstruction after transperineal brachytherapy for prostate cancer. Furthermore, TURP could compromise full-dose effective radiation delivery to the prostate. We analyzed the efficacy of the UroLume stent in treating the urinary outflow obstruction in such patients., Methods: Five patients who had undergone brachytherapy (3 with (192)Ir high-dose radiation and 2 with (125)I) subsequently developed one or more episodes of urinary retention 2 weeks to 4 years after treatment. The patients failed or could not tolerate alpha-blockers or clean intermittent catheterization. Three patients subsequently underwent urethral dilation/optical internal urethrotomy for strictures, and 1 patient underwent suprapubic tube placement. Following the failure of these interventions, each of these patients had a UroLume stent placement. A single UroLume stent (2 cm in 3 patients and 2.5 cm in 2 patients) was placed under local/spinal anesthesia., Results: All patients were able to void spontaneously immediately after stent placement. Of the patients with previous urethral strictures, 1 remained continent and 1 had persistent incontinence. Neither of the patients with early postbrachytherapy retention developed incontinence after stent placement. The main complaints following stent placement were referred pain to the head of the penis and dysuria. Stent-related symptoms necessitated stent removal in 2 of 5 patients, 4 to 6 weeks after placement., Conclusions: The UroLume stent can be used as an alternative form of therapy for managing postbrachytherapy bladder outlet obstruction. The treatment is easily reversible by removing the stent when obstruction resolves.

The exposure of endothelial cells to hypoxic environments regulates the expression of a number of genes with products that are vasoactive or mitogenic for vascular tissue, including platelet-derived growth factor, endothelin-1, and endothelial nitric oxide synthase. Hypoxia is also known to alter the adhesive properties of endothelium toward a variety of blood cell types. Thrombospondin-1 (TSP-1) is a glycoprotein with major roles in cellular adhesion and vascular smooth muscle proliferation and migration. We report here that hypoxia induces TSP-1 gene and protein expression. Oxygen tensions of < or =30 torr resulted in TSP-1 transcript induction initially apparent at 1 to 6 hours, with maximal induction (6.5-fold+/-1.2-fold) within 24 to 48 hours in both human and bovine endothelial cells. TSP-1 protein levels remain elevated after 72 hours of continuous hypoxic exposure. The induction of TSP-1 steady-state transcript levels is caused in large part, if not entirely, by post-transcriptional stabilization of the TSP-1 mRNA. The TSP-1 induction by hypoxia is a graded and reversible physiologic response and can be mimicked by the use of cobalt chloride or the inhibition of nitric oxide production, suggesting both the involvement of a heme-containing oxygen sensor and a role for the endogenous production of nitric oxide in TSP-1 regulation. The effects of hypoxia both on the stabilization of the TSP-1 transcript and the stimulation of TSP-1 protein production are completely inhibited by arginine butyrate.

Endothelial cell-generated nitric oxide (NO) accounts in large part for the labile vasodilator termed endothelium-derived relaxing factor. Two distinct types of NO synthase exist: a "constitutive' type (cNOS), found in endothelial cells, and an "inducible' enzyme. Endothelial cells sense pO2 levels in the range of 70-20 torr and respond to this hypoxia by inducing transcription of genes which encode the vasoactive proteins PDGF-B and endothelin-1. Exposure of human or bovine endothelial cells to low oxygen tensions results in a profound decrease in the transcript for cNOS and a corresponding fall in cNOS protein levels. The ability of endothelial cells exposed to hypoxia to produce NO in response to bradykinin, a stimulator of cNOS activity, was coordinately impaired. Cobalt inhibited the expression of cNOS transcripts, suggesting a mechanism comparable to that by which oxygen tension regulates expression of other vasoregulatory genes. In the presence of actinomycin-D, hypoxia had no effect on cNOS transcripts, suggesting that new gene transcription is required for cNOS suppression. The reducing agents PDTC and N-Ac did not mimic cNOS gene suppression by hypoxia, suggesting that this suppression is not related to the redox state of the intracellular environment. Thus, regulation of cNOS function in response to environmental factors can occur at the level of gene expression as well as at the level of enzyme activation.