Evan R. Goldfischer

ENDOSCOPIC MANAGEMENT OF URETERAL STRICTURES

PURPOSE We investigated and defined the role of endourological methods in the treatment of patients with ureteral stricture. MATERIALS AND METHODS A literature search was performed of the MEDLINE data base from 1978 through August 1996 concerning endoscopic treatment of patients with ureteral strictures. Additional articles from before 1978 were also selectively included. RESULTS Many endourological methods are available to treat patients with ureteral strictures. Ureteral dilation via an antegrade or retrograde approach may be accomplished in most cases with varying rates of success depending on stricture etiology, location and length. Endoscopic ureterotomy may also lead to long-term patency in select cases and appears to be superior to dilation alone in patients with anastomotic ureteral strictures. However, no randomized studies comparing endourological methods in the treatment of ureteral stricture disease were found. CONCLUSIONS Significant advances in technique and technology have led to an improved ability to treat ureteral strictures without the need for open surgery in many patients.

Randomized, prospective, double-blind study of the effects on pain perception of lidocaine jelly versus plain lubricant during outpatient rigid cystoscopy.

PURPOSE There is no clear evidence that intraurethral lidocaine jelly decreases pain and/or makes rigid cystoscopy more tolerable for patients. Since lidocaine jelly is significantly more expensive than plain lubricant, we attempted to assess the true benefit of this agent. MATERIALS AND METHODS We performed a randomized, prospective, double-blind study to compare the anesthetic effects of intraurethral 2% lidocaine jelly versus plain lubricant in patients undergoing rigid cystoscopy. Unlike previous studies, we ensured adequate urethral filling by using 30 cc of each agent and we waited 20 minutes after instillation of the agent before performing cystoscopy to allow adequate absorption. Cystoscopy was performed using a 17 to 21F rigid instrument. A total of 189 patients was entered into the study but 10 were excluded from analysis due to incomplete questionnaires. A 10-point scale (1-least to 10-most painful) was used to measure pain perception. RESULTS In men pain perception was significantly decreased when lidocaine jelly was used (mean plus or minus standard error 3.00 +/- 0.21 versus 4.36 +/- 0.37 points, p = 0.002). In women there was no observed difference in pain perception when lidocaine jelly or plain lubricant was used (3.21 +/- 0.38 versus 3.11 +/- 0.30 points, p = 0.823). Patient race, performance of a related procedure, cystoscope size or history of cystoscopy did not significantly affect reported pain scores. There was a slight decrease in pain perception with increasing age (-0.23 +/- 0.10 points per decade, p = 0.021). The level of patient anxiety before cystoscopy was also significantly associated with pain perception (p < 0.001). CONCLUSIONS Lidocaine jelly offers no advantage over plain lubricant in regard to pain control during rigid cystoscopy in women. However, when used in adequate amounts and allowed to dwell in the urethra for 20 minutes before cystoscopy, lidocaine jelly can significantly decrease pain in men.

Assessing the Impact of Ureteral Stent Design on Patient Comfort

PURPOSE We assessed the near term comfort of newly designed ureteral study stents or marketed control stents, including Polaris and Percuflex stents. Study stents had distal 6Fr pigtail ends with 3Fr or less loops. Decreased material in situ was hypothesized to enhance comfort. Usefulness of the patient self-administered Ureteral Stent Symptoms Questionnaire (Stone Management Unit, Southmead Hospital, United Kingdom) was assessed. MATERIALS AND METHODS This 4-arm multicenter study enrolled adults requiring retrograde unilateral ureteral stent placement for 4 to 28 days. Ureteral Stent Symptoms Questionnaire administration was done before placement (baseline), on day 4 after placement and on day 30 after removal. A total of 236 patients were randomized in a 1:1:1:1 ratio to the short loop tail stent (60), the long loop tail stent (59), the Percuflex Plus stent (64) and the Polaris stent (53). RESULTS Overall pain worsened from baseline to day 4 and improved from days 4 to 30. Mean pain medication use peaked for all stents on day 1 after placement. Common device related symptoms were mild or moderate in severity, including flank pain in 47 patients, hematuria in 39, dysuria in 34, frequent urination in 30 and urinary urgency in 27. Six patients experienced a total of 9 device related adverse events requiring hospitalization. All adverse events resolved, including most within 3 days of inpatient treatment. CONCLUSIONS Although it was not statistically significant, patients stented with the short loop tail had lower questionnaire pain scores on day 4 after placement and lower pain medication use on day 1 after placement when pain peaked in all stent groups, suggesting that ureteral stent comfort, especially pain, may be improved by less material in situ. The Ureteral Stent Symptoms Questionnaire may be better suited for longer term comparisons in stented vs nonstented patients, rather than in this short-term ureteral stent trial.

EVALUATION OF CHANGES IN PROSTATE SPECIFIC ANTIGEN IN CLINICALLY LOCALIZED PROSTATE CANCER MANAGED WITHOUT INITIAL THERAPY

PURPOSE We define changes in prostate specific antigen (PSA) measurements with time in 49 men 71.9 +/- 7.0 years old (mean plus or minus standard deviation) with clinically localized prostate cancer who remain untreated. MATERIALS AND METHODS We retrospectively analyzed PSA changes in prostate cancer patients managed by watchful waiting. In all patients a minimum of 3 PSA levels were measured at intervals of at least 6 months after malignancy was diagnosed. The rate of change in serum PSA level with time (PSA velocity) was determined using an exponential, log linear model. RESULTS In 49 patients treated conservatively mean initial PSA level plus or minus standard deviation was 12.3 +/- 11.1 ng./ml. and mean PSA followup during which no therapy for prostate cancer was introduced was 32.1 +/- 13.2 months. PSA levels decreased during the observation period in 11 of the 49 patients (22%) and median PSA doubling time in the remaining 38 was 55.7 months (range 15.1 to 994.5). There was no significant correlation between age at diagnosis, Gleason sum, initial PSA level or clinical stage and PSA velocity. The short-term rate of change in PSA during the first 9 months after prostate cancer was diagnosed correlated poorly with overall PSA velocity. The short-term rate of PSA change was greater than the overall rate of change in 14 of 37 patients (38%). CONCLUSIONS There is significant variability in the rate of change of PSA with time in men with clinically localized prostate cancer who remain untreated. The usefulness of serial PSA measurements in the management of watchful waiting is unclear. Changes in PSA may not be helpful or appropriate in determining the need for therapy after a period of observation.

Efficacy and Safety of Tadalafil 5 mg Once Daily for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Subgroup Analyses of Pooled Data From 4 Multinational, Randomized, Placebo-controlled Clinical Studies

OBJECTIVE To assess the efficacy and safety of tadalafil, a phosphodiesterase 5 (PDE5) inhibitor efficacious for erectile dysfunction and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), in population subgroups, using pooled data from 4 international, randomized, placebo-controlled studies in men with LUTS/BPH. METHODS The safety database included 1500 men randomized to tadalafil 5 mg once daily or placebo for 12 weeks. Changes in total International Prostate Symptom Score (IPSS), IPSS-quality of life index, and BPH impact index were examined overall, and changes in IPSS or adverse events (AEs) were examined across subgroups of interest. Treatment-group differences were assessed using analysis of covariance. RESULTS Results of pooled data confirmed that tadalafil (N = 752) resulted in significant improvements from baseline vs placebo (N = 746) in IPSS (mean difference -2.3; P <.001), and also in BPH impact index and IPSS-quality of life index (both P <.001). Subgroup analyses demonstrated that IPSS improvements were significant regardless of baseline LUTS severity (IPSS <20/≥20), age (≤65/>65 years), recent previous use of α-blockers or PDE5 inhibitors, total testosterone level (<300/≥300 ng/dL), or prostate-specific antigen predicted prostate volume (<40/≥40 mL). [corrected] Rates of treatment emergent AEs were comparable between subgroups of baseline age (≤65/>65 years), previous PDE5 inhibitor use, and the presence or absence of pre-existing diabetes, hypertension, or cardiovascular disease (including hypertension), but somewhat higher for recent previous α-blocker use. CONCLUSION In these pooled data analyses, tadalafil 5 mg improved LUTS/BPH across subgroups of age, LUTS severity, testosterone levels, and prostate volume. Rates of AEs were similar across the subgroups assessed.

Laparoscopic creation of a continent cecal tube for antegrade colonic irrigation.

UNLABELLED OBJECTIVES; The antegrade continence enema (ACE) procedure has been used for the treatment of overflow fecal incontinence or constipation inpatients with spina bifida. The procedure requires an appendiceal reimplantation into the cecum with creation of a continent abdominal stoma for antegrade colonic washout. To preserve the appendix for potential use in urinary diversion, we developed two surgical techniques for tubularizing an antimesenteric cecal segment to use in place of the appendix. METHODS The surgery was performed in 6 dogs. The first two procedures used an open surgical technique through a 10-cm midline laparotomy. The cecum was isolated, and a small cecotomy was made. A 10F red rubber catheter was introduced into the cecotomy, and a 4-cm length of cecum was tubularized along its antimesenteric border with a gastrointestinal anastomosis stapler over the catheter. A nipple was created at the base of the tube to enhance continence, and the tubular segment was brought through the lower abdominal wall to create a catheterizable stoma. After our success, four subsequent procedures were performed laparoscopically to create the same tubularized cecal segment. A 4-cm antimesenteric tubularized cecal segment with sufficient lumen to accommodate a 10F to 12F catheter was constructed using a laparoscopic gastrointestinal anastomosis stapler. Rather than creating a nipple at the base of the tubular segment, continence of the stoma was achieved by tunneling the cecal tube through a 2-cm lower quadrant subcutaneous tunnel. A flush stoma was then created and secured to the skin. RESULTS Stoma viability was grossly confirmed in all 6 dogs during the postoperative period, with no incidence of bowel obstruction. Slight fecal leakage through the stoma was observed in 1 dog with a laparotomy but not in those with laparoscopy. Catheterization was easily performed in all dogs with a 10F red rubber catheter during the postoperative period. The dogs were killed on postoperative day 10, and gross anatomic and histologic examination of the cecal segment confirmed luminal patency and viability. CONCLUSIONS Open and laparoscopic continent cecostomies were successfully constructed in a canine model and are likely to be applicable to humans with neuropathic constipation.

Serum creatinine measurements in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia

OBJECTIVES To determine the usefulness of routine serum creatinine measurements in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) and to correlate these findings with patient age, symptom severity, and comorbid diseases. METHODS We analyzed serum creatinine measurements in 246 consecutive men presenting for evaluation of voiding symptoms and BPH. Multiple logistic regression analysis was used to determine whether the International Prostate Symptom Score (IPSS), quality-of-life measure from the IPSS, patient age, or a history of diabetes mellitus or hypertension predicted abnormal creatinine levels. RESULTS An elevated serum creatinine level was noted in 11% (26 of 245) of evaluable patients. Only a history of diabetes or hypertension predicted the presence of renal insufficiency. Among men with no history of comorbid disease, increasing age was significantly associated with the finding of an abnormal creatinine. Neither the overall symptom score nor the quality-of-life measure was significantly associated with the likelihood of detectable renal dysfunction. CONCLUSIONS Medical renal disease secondary to diabetes or hypertension appears to be the most likely cause of elevated serum creatinine measurements in men with BPH and renal insufficiency. We were unable to identify subgroups of patients in whom the risk of renal dysfunction is sufficiently low to avoid routine serum creatinine measurements.

Omphalopagus Twins With Covered Cloacal Exstrophy

The incidence of conjoined twins is approximately 1/100,000 births and 70% of the twins are female.’ Approximately 40 to 60% of conjoined twins are stillborn and an additional 35% survive only 1 day. These early deaths generally occur in the most severely malformed twins, especially those with thoracopagus joining and major cardiopulmonary malformation. Approximately 35% of the twins are the omphalopagus type, which comprises a wide spectrum ranging from shared liver, intestines and bladder to a mere skin bridge.* We report the anatomical findings and separation of the eighteenth reported case of minimally conjoined omphalopagus twins.3

Efficacy and safety of oxybutynin topical gel 3% in patients with urgency and/or mixed urinary incontinence: a randomized, double-blind, placebo-controlled study.

To assess the efficacy and safety of oxybutynin transdermal gel 3% (OTG3%), with propylene glycol for enhanced skin permeation, in patients with urinary incontinence (UI).

A Return to Normal Erectile Function with Tadalafil Once Daily after an Incomplete Response to As-Needed PDE5 Inhibitor Therapy

INTRODUCTION An optimal outcome of an erectile dysfunction (ED) treatment is to enable a return to normal erectile function (as defined by an International Index of Erectile Function-Erectile Function [IIEF-EF] domain score ≥ 26). As-needed (PRN) phosphodiesterase type 5 (PDE5) inhibitor treatment does not always result in a return-to-normal erectile function. AIM The combined studies evaluated whether treatment with tadalafil once daily would allow men to return to normal erectile function who had less than normal IIEF-EF domain scores while using a maximum dose of a PRN PDE5 inhibitor treatment. METHODS Men were ≥ 18 years of age, sexually active, reported a ≥ 3-month history of ED, and had been taking the maximum dose of sildenafil citrate, vardenafil, or tadalafil PRN. Randomization to once-daily therapy with tadalafil 2.5 mg to 5 mg (N = 207), tadalafil 5 mg (N = 207), or placebo (N = 209) for 12 weeks followed a 4-week maximum dose PRN PDE5 treatment and 4-week nondrug lead periods. Two identical double-blind, randomized, placebo-controlled studies were conducted; combined results are reported. MAIN OUTCOME MEASURE The main outcome measure was the percentage of subjects with a return-to-normal erectile function (IIEF-EF domain score ≥ 26) when treated with tadalafil once daily compared with placebo. RESULTS In subjects not achieving normal erectile function with the maximum dose of a PRN PDE5 inhibitor, a higher percentage of subjects treated with tadalafil had an IIEF-EF domain score ≥ 26 at end point (tadalafil 2.5- to 5-mg group [39%]; tadalafil 5-mg group [40%]) compared with the placebo group (12.1%; P < 0.001). Tadalafil was generally well tolerated and adverse events observed were consistent with previous reports of tadalafil once daily. CONCLUSIONS Treatment with tadalafil once daily significantly improved erectile function in men with mild to mild-moderate impairments in erectile function following PRN PDE5 inhibitor treatment.