Effects of ischemia on human renal interstitial fluid metabolites.

PURPOSE: Microdialysis is a technique for monitoring the concentration of molecules in the interstitial fluid of living tissue. We report the effects of ischemia on human renal interstitial fluid molecules. MATERIALS AND METHODS: Ten patients with a renal mass or upper tract transitional cell carcinoma who elected laparoscopic nephrectomy or nephroureterectomy were studied with in situ renal microdialysis. Microdialysate was continuously collected into separate vials every 10 minutes before and after the renal artery was stapled. Samples were analyzed for the glucose, pyruvate, lactate and glycerol concentration. RESULTS: The concentration of all 4 molecules was stable throughout the pre-ischemia baseline period. Glucose and pyruvate concentrations decreased to almost zero during the first 60 minutes of ischemia. Lactate increased during the initial 60 minutes of ischemia and then plateaued with continued ischemia. The glycerol concentration increased directly throughout the ischemia time. CONCLUSIONS: The trends of human interstitial metabolite concentrations during ischemia are similar to trends found in the porcine model. The human renal interstitial glycerol concentration increases directly throughout the duration of ischemia and serves as a marker of nephron damage. Microdialysis is a tool that provides real-time, renal unit specific, minimally invasive data on the metabolic status of the human kidney during ischemia. It may be helpful for avoiding permanent renal ischemic injury.

Predicting irreparable renal ischemic injury using a real-time marker in the porcine model.

PURPOSE: We determined the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function. MATERIALS AND METHODS: Using a single kidney model 3 groups of 5 pigs each underwent 120, 150 and 180 minutes of warm ischemia, respectively. Microdialysis samples were collected before, during and after ischemia. Renal function assessments consisting of serum creatinine and GFR measurements were performed before ischemia and on post-ischemia days 1, 5, 9, 14 and 28. Kidneys exposed and not exposed to ischemia were collected for histological study. RESULTS: Interstitial glucose and pyruvate concentrations decreased, while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered, while glycerol increased throughout warm ischemia time. At post-ischemia day 28 renal function returned to pre-ischemia baseline levels in the group with 120 minutes of ischemia but did not recover to baseline in the 150 and 180-minute ischemic groups. Functional data correlated with histological findings. The 120-minute maximal renal tolerance of warm ischemia correlated with a mean +/- SD glycerol concentration of 167 +/- 24 micromol/l. CONCLUSIONS: Interstitial glycerol is a real-time, renal unit specific, minimally invasive marker of renal function deterioration. Exposure of porcine kidneys to ischemic insults resulting in renal cortical interstitial glycerol concentrations higher than 167 micromol/l is associated with irreparable functional damage in this model.

Real-time analysis of renal interstitial metabolites during induced renal ischemia*.

PURPOSE: Microdialysis is an innovative technique used to monitor the chemistry of the interstitial fluid in living tissue. We documented changes in concentration of interstitial fluid metabolites before, during, and after induced renal ischemia. MATERIALS AND METHODS: Under general anesthesia, a microdialysis probe was laparoscopically positioned into the renal cortex of six pigs. Isotonic sterile perfusion fluid was pumped through the probe at 2 microL/min. After collecting a baseline sample, the renal artery was occluded with a Satinsky clamp for 90 (n = 3) or 120 (n = 3) minutes. A dialysate sample was collected every 30 minutes during the ischemic and 3-hour postischemic period. The samples were analyzed for glucose, lactate, pyruvate, glutamate, urea, and glycerol concentrations with the CMA/600 Microdialysis Analyzer. Serum metabolic panels from peripheral venous samples drawn before ischemia, after ischemia, and 3 hours after ischemia were analyzed. RESULTS: Glucose and pyruvate concentrations significantly declined (P = 0.01, P = 0.05, respectively) while lactate and glycerol concentrations significantly increased during ischemia (P = <0.01, P < 0.01, respectively). Glutamate increased to 2.5 times the baseline concentration (P < 0.01) at 1 hour of ischemia and subsequently declined during ischemia. The lactate/pyruvate ratio increased sharply during ischemia and returned to baseline within 1 hour postischemia. There were no changes noted in serum creatinine levels before and after ischemia. CONCLUSIONS: Microdialysis can accurately measure minute real-time changes in the renal interstitial environment caused by ischemia not detected with serum studies. These local changes may be correlated with ischemic times to predict tissue preservation in future studies.

The influence of finasteride on the development of prostate cancer.

BACKGROUND: Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. METHODS: In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. RESULTS: Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. CONCLUSIONS: Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

Resident education outcomes and perception of a seminar format to teach female pelvic anatomy and procedures to correct pelvic prolapse.

Urologic residents need to learn basic and applied knowledge of female pelvic anatomy, a subject rarely taught beyond preclinical undergraduate medical education. This study tests the hypothesis that urologic resident knowledge of female pelvic anatomy and prolapse may be enhanced with a seminar. Twenty residents attended a one day seminar combining didactics and a cadaveric dissection related to female pelvic anatomy and female pelvic prolapse conditions. Resident knowledge was measured with a multiple choice test administered in a pretest-posttest experimental design. Resident attitudes toward the seminar were assessed by a 20 item survey using a strongly disagree to strongly agree scale. Pretest and posttest mean scores were 55% and 71% respectively, p=.0007 (Kuder-Richardson 20 coefficients were 0.7). Questionnaire responses indicated positive opinions regarding the educational value of the seminar. Urologic resident knowledge of female pelvic anatomy and pelvic prolapse conditions may be enhanced by conducting a one day teaching seminar.

The treatment of posterior compartment vaginal defects.

Posterior compartment prolapse can be thought of as a relaxation or separation of the tissues of the rectovaginal septum and perineal body. This article reviews the pathophysiology, diagnosis, and surgical management of rectoceles and relaxed vaginal outlet. With proper treatment, a continued active lifestyle and improved quality of life usually can be restored; however, this result requires a thorough understanding of pelvic anatomy and pathophysiology and experience in performing the appropriate surgical procedures.

Lapra-Ty holding strength and slippage with various suture types and sizes.

OBJECTIVES: To investigate the holding strength and slippage of Lapra-Ty clips on various suture types and sizes. METHODS: Using an automated materials testing system with the Lapra-Ty in a fixed position, Lapra-Ty holding strength and displacement were determined with 0, 2-0, 3-0, and 4-0 Vicryl, Monocryl, and polydioxanone suture (PDS). To simulate clinical application, Lapra-Tys were also tested by applying a load to these sutures after being passed through a full-thickness layer of tautly suspended fresh porcine bladder tissue. Three trials were performed with each suture type and size. RESULTS: The Lapra-Ty holding strength with Vicryl suture was significantly higher than with Monocryl or PDS of the same suture size in bladder tissue trials. Monocryl suture had a significantly higher displacement than Vicryl or PDS of the same suture size in bladder tissue trials (except for 4-0 Monocryl and PDS having insignificantly different displacements). Lapra-Tys slipped off Vicryl, Monocryl, and PDS in 25%, 67%, and 67% of their respective trials. Lapra-Tys did not slip during any of the trials with 2-0 suture of any type or 3-0 Vicryl. Lapra-Tys with holding strengths on suture less than approximately 8 Newtons (N) slipped and greater than 8 N pulled through the bladder tissue without slipping. CONCLUSIONS: The optimal suture type and size to maximize Lapra-Ty holding strength and minimize slippage was determined to be 2-0 and 3-0 Vicryl, 2-0 Monocryl, and 2-0 PDS. Monocryl suture stretches more than Vicryl and PDS at higher loads.

The effects of ureteral mobilization and transection on ureteral oxygenation.

OBJECTIVES: To determine the impact of ureteral transection with and without prior ureteral mobilization on ureteral oxygen partial pressure (p(u)O(2)). METHODS: Sixteen pigs underwent general anesthesia with laparoscopic transperitoneal access to the right ureter. With no dissection and minimal manipulation, a tissue oxygen probe (Licox, Kiel, Germany) was introduced via a trocar and inserted into the ureter. The probes were placed at the ureteropelvic junction (UPJ, n = 8) and ureterovesical junction (UVJ, n = 8). Baseline p(u)O(2) was measured. Subsequently, half of the animals at each level (n = 4) underwent complete ureteral transection proximal to UPJ probes and distal to UVJ probes with or without prior mobilization. p(u)O(2) levels were measured after ureteral mobilization and transection. RESULTS: Of the ureters transected at the UPJ without mobilization, the mean p(u)O(2) level declined by 13 mm Hg relative to baseline (P = 0.07). The baseline UPJ p(u)O(2) level declined by 5 mm Hg after ureteral mobilization alone and subsequently by 31 mm Hg after transection (P <0.01). Of the ureters transected at the UVJ without mobilization, the p(u)O(2) level decreased by 4 mm Hg relative to baseline (P = 0.08). The baseline UVJ p(u)O(2) level decreased by 15 mm Hg after ureteral mobilization alone and subsequently by 39 mm Hg after transection (P <0.01). At both the UPJ and UVJ, the transected-only p(u)O(2) level was statistically higher than the mobilized and transected level (P = 0.03, respectively). CONCLUSIONS: During ureteral surgery, mobilization alone exposes the distal ureter to more ischemia than the proximal ureter, and efforts to minimize ureteral mobilization when transection is necessary are crucial in maintaining tissue oxygenation.

Feasibility of laparoscopic renal cooling with near-freezing saline irrigation delivered with a standard irrigator aspirator.

OBJECTIVES: To determine the feasibility of laparoscopic renal cooling with near-freezing saline irrigation in the porcine model delivered using readily available operating room equipment. METHODS: Five pigs underwent laparoscopic renal surgery with temperature sensors placed in the medulla and upper, middle, and lower pole renal cortex. After complete occlusion of the renal artery and vein, near-freezing saline was delivered with a standard irrigator/aspirator onto the renal surface. The run-off was simultaneously suctioned as it pooled in the hilum with a second aspirator. The kidney and body temperatures were monitored throughout the 1-hour ischemic period and for 10 minutes after unclamping the hilum. RESULTS: Continuous irrigation of the kidney with near-freezing saline in the first pig resulted in hypothermic renal (13.8 degrees C) and core body (33.1 degrees C) temperatures. For the subsequent four pigs, irrigation was limited to the first 5 minutes of ischemia to achieve renal cortical and medullary temperatures of less than 20.0 degrees C within 6 and 8 minutes of ischemia, respectively. Subsequently, the kidney was irrigated for 1 minute every 12 to 14 minutes to maintain renal temperatures of less than 20.0 degrees C. The core body temperatures decreased from a mean baseline of 37.0 degrees to 35.4 degrees C using the intermittent irrigation technique. Our early clinical experience with near-freezing saline intermittent irrigation during laparoscopic partial nephrectomy with 10 patients showed stable core body temperature and serum creatinine with a mean ischemic time of 48 minutes. CONCLUSIONS: Using standard, readily available laparoscopic irrigator/aspirators, renal cooling during laparoscopic partial nephrectomy with near-freezing saline creates acceptable renal tissue temperatures for preservation of renal function.

Shock wave lithotripsy success for renal stones based on patient and stone computed tomography characteristics.

OBJECTIVES: To determine the patient and noncontrast computed tomography (NCCT) stone characteristics that predict either of 2 extracorporeal shock wave lithotripsy (ESWL) outcomes: stone-free (SF) status or ESWL success. METHODS: The records of 200 consecutive patients with nephrolithiasis treated with ESWL were reviewed. Patient age, sex, stone laterality, body surface area, body mass index, maximal stone dimension, mean stone Hounsfield units (HU), stone Hounsfield density, skin-to-stone distance (SSD), and intrarenal stone location were studied as potential predictors. Patients with no calcifications on postoperative kidneys, ureters, and bladder (KUB) at 6 weeks were defined as SF. ESWL success was defined as SF or remaining stone fragments less than 4 mm. RESULTS: Intrarenal stone location was found to be the only predictor of SF status. Renal pelvic/ureteropelvic junction (UPJ) stones cleared better than calyceal stones, and upper/middle calyceal stones cleared better than lower calyceal stones. Stone size, mean HU, and location predicted ESWL fragmentation success. Smaller stones and stones with lower mean HU levels were more successfully fragmented. Higher SF and ESWL success rates were found with a shorter SSD among calyceal stones when renal pelvic/UPJ stones were excluded from analysis. CONCLUSIONS: Stone location is the most important factor in achieving SF status after ESWL. NCCT stone characteristics such as stone size, mean HU, and intrarenal location are important predictors of ESWL success.

Transurethral collagen injections for male intrinsic sphincter deficiency: the University of Texas-Houston experience.

PURPOSE: Injectable agents are used to increase urethral coaptation for the treatment of intrinsic sphincter deficiency. We evaluated the long-term results and complications of transurethral collagen injections in males. MATERIALS AND METHODS: We reviewed the charts of 322 men (mean age 67.2 years, range 40 to 91) with intrinsic sphincter deficiency after therapy for prostate carcinoma (307) or benign prostatic hyperplasia (15) who received transurethral collagen injections. The analysis included types and combinations of treatment for prostate cancer or benign prostatic hyperplasia, pre-procedure voiding symptoms, total collagen received, maximal percentage improvement and durability of effect. RESULTS: The mean length of followup was 40.1 (+/-13.2) months. Overall, the mean number of injections was 4.37 (+/-2.09). Mean percent improvement after a series of injections was 44.59 (+/-38.26). Mean pad use before and after injection was statistically different (5.15 vs 2.98, p=0.0001). Mean duration of response was 6.3 (+/-8.14) months. In those who achieved complete continence (17%), the mean duration of response was 11.1 (+/-8.87) months. Within this group the mean number of injections and ml of collagen injected were 3.83 and 29.27, respectively. Five patients (1.5%) complained of a quantitative increase in leakage after their series of collagen injections. CONCLUSIONS: Transurethral collagen injections are a good option for short-term therapy in men with post-prostatectomy incontinence. The mean number of injections to achieve a plateau is 3 to 4, regardless of initial severity of incontinence. Those in the radical prostatectomy only treatment group are statistically more likely to achieve continence than all other treatment groups.

Prospective long-term results and quality-of-life assessment after Dura-II penile prosthesis placement.

OBJECTIVES: To evaluate prospectively the long-term device reliability and patient satisfaction after Dura-II malleable penile prosthesis implantation. METHODS: Between 1992 and 1996, 94 patients underwent Dura-II implantation for erectile dysfunction. Patients were prospectively examined and completed standardized questionnaires regarding sexual activity, prosthesis function, intercourse satisfaction, and overall quality of life. An independent statistician analyzed these data. RESULTS: The mean patient age was 63 years, and the mean patient follow-up was 5.7 years. Eighty-five patients were available for long-term evaluation. Fourteen patients died during the follow-up period. One patient was lost to follow-up, and eight prostheses (9%) were explanted; however, no mechanical defects were found in the explanted prostheses. Seventy-six percent and 87% of patients reported satisfactory rigidity and ease of concealing the device, respectively. Seventy-six percent of patients remained sexually active during the evaluation period, and 87% of patients reported that the prosthesis improved their overall quality of life. Eighty-five percent would undergo the implant surgery again, and 88% percent of patients would recommend the Dura-II prosthesis to a friend. CONCLUSIONS: The Dura-II malleable penile prosthesis provides good rigidity, ability to conceal the device, and mechanical reliability, as demonstrated by the results of this long-term study. Most patients stated they would have the prosthesis placed again and would recommend it to a friend.

Unusual presentation of hidradenitis suppurativa with massive enlargement of penis.

Hidradenitis suppurativa is a chronic, recurrent inflammatory disease affecting the cutaneous apocrine glands and resulting in their obstruction. This enigmatic disease causes recurrent episodes of infection, edema, scarring, and fibrosis of surrounding tissues. We present the case of a 55-year-old man with two decades of inguinal hidradenitis suppurativa that resulted in extensive penile subcutaneous lymphedema and enlargement secondary to scarring and obstructive lymphadenopathy. Reconstructive phalloplasty to restore normal penile function was required. Minimal recurrent induration, normal cutaneous sensation, and normal voiding and erectile function were noted at 3 years of follow-up.

Questionnaire-based outcomes of urinary incontinence and satisfaction rates after radical prostatectomy in a national study population.

OBJECTIVES: To assess the incidence of incontinence and the associated quality of life in men younger than 65 years of age after radical prostatectomy. METHODS: The TRICARE/CHAMPUS database was searched to identify 1000 patients who underwent radical prostatectomy within 2 years before study initiation. All patients were younger than 65 years of age at the time of surgery and had at least 18 months of postoperative follow-up. An eight-part questionnaire focusing on continence after surgery was mailed to the study population. Respondents reported on voiding dysfunction, degree of incontinence, satisfaction with continence, and lifestyle impact of incontinence. RESULTS: A total of 674 eligible patients (78%) completed the survey. Any amount of pad use or changing of underwear to keep dry was reported by 31.7%, leakage once per day occurred in 16.8%, and leakage more than once per day in 9.2%. Severe urgency or urge incontinence occurred in 17.4% and was the primary cause of incontinence in one third of patients with incontinence. Only 8.9% of patients used two or more pads per day, and severe incontinence (more than four pads per day) occurred in 2.7%. Incontinence-corrective surgery was used by 4.9% of patients. Overall, 83.3% of patients reported satisfaction with their continence after surgery, and 12% considered postoperative incontinence to be a problem. CONCLUSIONS: The results of this questionnaire-based outcomes evaluation of a large national sample of prostatectomy patients younger than 65 years of age demonstrate that incontinence rates in this younger population are similar to those in the Medicare population and may be more representative of the national experience than single-center reports.

Long-term results of Ingelman-Sundberg denervation procedure for urge incontinence refractory to medical therapy.

PURPOSE: Urge incontinence refractory to anticholinergic medication and behavioral techniques is a therapeutic challenge. We evaluated the durability of the modified Ingelman-Sundberg detrusor denervation procedure as minimally invasive surgical therapy for intractable urge incontinence. MATERIALS AND METHODS: Patients presenting with severe urge incontinence unresponsive to medical and/or behavioral therapy were injected subtrigonally with 10 ml. 0.25% bupivacaine. The patients were contacted 24 hours later to determine whether they experienced a decrease in urgency and urge incontinent episodes. The 28 patients with temporary resolution of symptoms were offered operative management. All patients were evaluated with history, physical examination and fluoroscopic urodynamics. The procedure consists of transvaginal dissection of the perivesical fascia from the area of the trigone, including sharp division of the terminal branches of the pelvic nerve. RESULTS: A total of 28 patients 28 to 83 years old (mean age 54.6) underwent the Ingelman-Sundberg procedure from April 1993 to September 1997. All patients presented with a history of urge incontinence, 10 reported concomitant stress incontinence and 10 had documented unstable detrusor contractions on urodynamic evaluation. Needle suspension and the pubovaginal sling procedure were performed with the Ingelman-Sundberg procedure in 1 case each. Mean followup was 44.1 months (range 14 to 67). Of the patients 15 (54%) achieved the complete durable resolution of urge incontinence, 4 (14%) were improved and 9 (32%) were unchanged. CONCLUSIONS: Ingelman-Sundberg bladder denervation resulted in a 68% long-term cure or improved rate in a difficult patient population, namely those with intractable urge incontinence. This brief, minimally invasive procedure is an excellent alternative to more aggressive surgical options.