Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate.

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.

AIMS: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. METHODS: This was a 12-week, open-label, flexible-dose study of adults with OAB (> or = 8 micturitions and > or = 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject's and physician's subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. RESULTS: Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p < 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement > or = 2 points. Significant improvements from baseline (p < 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified. CONCLUSION: Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.

Sildenafil citrate efficacy 8 h postdose in men with mild to moderate erectile dysfunction.

In two randomized, double-blind, placebo-controlled trials of 100 mg sildenafil citrate, men (N=601) with mild to moderate erectile dysfunction (ED) attempted intercourse 8 h (range, 7-9 h) postdose. The baseline to end-of-treatment improvement in the sildenafil groups vs placebo was greater (P<0.001) for the per-patient proportion (PPP) of 'yes' responses to the Sexual Encounter Profile question 3 (SEP3: successful intercourse (primary outcome)) (odds ratio (OR)=3.2 (trial 1), 7.6 (trial 2) and 5.6 (pooled data)); PPP of erection hardness score 4 (EHS 4, completely hard and fully rigid) (OR=6.2 (trial 1) and 10.9 (trial 2)); scores on the International Index of Erectile Function; and other EHS and SEP outcomes. Two to three times as many men were satisfied with sildenafil vs placebo treatment (Erectile Dysfunction Inventory of Treatment Satisfaction Index >50). Thus, responsiveness to 100 mg sildenafil may persist for 8 h postdose in men with mild to moderate ED.

Acute ureteral elongation in two animal models using a balloon expander.

BACKGROUND AND OBJECTIVE: Repair of ureteral injuries and strictures often necessitates a major reconstructive procedure such as a psoas hitch, Boari flap, renal mobilization, ileal interposition, or autotransplantation. Tissue expanders have been used to elongate nerves and arteries. We examined the effects of acute ureteral elongation in two animal models. MATERIALS AND METHODS: In eight female rabbits, we exposed the left ureter through a midline incision and placed a Ruiz-Cohen balloon beneath the undermined portion. The expander was then inflated until the ureter was tightly stretched across it. After deflation, the expanded segment was measured in situ and compared with its original length. Follow-up urography was performed, and the tissue was harvested and examined by a pathologist. The same procedure was performed in five pigs; however, in these animals, a segment of ureter was excised, and a ureteroureterostomy was performed, after the acute expansion. RESULTS: We were able to achieve acute elongation of the expanded ureteral segment. The mean elongation was 31.3% in the rabbits and 32.0% in the pigs. An intravenous urogram (IVU) 6 weeks after the elongation showed a functioning kidney and a patent ureter. Histologic examination of the ureter within 24 hours after the expansion revealed that all segments were viable, the luminal epithelium was intact, and the muscular layers appeared normal. At 6 weeks, the expanded segment showed mild inflammatory changes, but the overall morphology, size, and cytology findings were similar to those of a normal control. CONCLUSIONS: Acute ureteral elongation using a tissue expander is a new method of increasing ureteral length. It may be useful to cover defects that would need major operations with greater morbidity.

Failed endopyelotomy: low expression of TGF beta regardless of the presence or absence of crossing vessels.

BACKGROUND AND OBJECTIVE: Endopyelotomy relies on Davis' intubated ureterotomy principle of healing by secondary intention and smooth-muscle regeneration. Approximately 15% of endopyelotomies fail, and the restrictured segment almost always shows evidence of reactive fibrosis with little smooth-muscle regeneration. Previous data suggests that an elevation of TGF beta in obstructed ureteropelvic junctures may be necessary for successful tissue repair following endopyelotomy. The role of crossing vessels in endopyelotomy failure is very controversial. To better understand the pathophysiology of endopyelotomy failure, the expression of transforming growth factor-beta (TBG beta) in patients with a failed endopyelotomy and crossing vessels was compared with that in patients without crossing vessels, as well as those having primary pyeloplasty or a normal ureteropelvic junction (UPJ). MATERIALS AND METHODS: The expression of TGF beta was detected immunohistochemically in slide-mounted thin sections (4 microns) cut from paraffin-blocked adult UPJ segments obtained during primary pyeloplasty (N = 11), secondary pyeloplasty after failed endopyelotomy with documented crossing vessels (N = 10), secondary pyeloplasty after failed endopyelotomy without crossing vessels (N = 11), and normal UPJs removed during nephrectomy for purposes unrelated to obstruction (N = 11). Expression was graded on a scale of 0 to 4. RESULTS: The combined failed endopyelotomy group had a significantly (P < 0.05) lower level of TGF beta (1.9 +/- 0.7) than did primary obstructed UPJs (2.6 +/- 0.7). The TGF beta level in the crossing vessels group (1.9 +/- 0.7) did not differ from that in the group without crossing vessels (1.8 +/- 0.7), nor did it differ from that in the group with normal UPJs (1.6 +/- 0.7). As expected, primary obstructed UPJs had a significantly higher level of TGF beta than normal ones (P < 0.02). CONCLUSIONS: Obstructed UPJs that had failed endopyelotomy had a similarly reduced level of TGF beta whether or not crossing vessels were present. These data suggest that an elevation of TGF beta in obstructed UPJs may be necessary for successful tissue repair after endopyelotomy and that the presence of crossing vessels is probably not relevant.

Complete renal embolization as an alternative to nephrectomy.

PURPOSE: Simple nephrectomy is technically demanding in patients with recurrent inflammation or bleeding. It is also unwise to subject patients in poor health to the rigors of an extensive operative procedure. We report our experience with complete renal embolization as a safe and reliable alternative to surgical nephrectomy. MATERIALS AND METHODS: Eight patients underwent complete renal embolization as an alternative to nephrectomy. Patients were given antibiotics intravenously before and after embolization. Six patients with indwelling nephrostomy tubes received post-embolization instillation of 80 mg. gentamicin before tube removal. Narcotic analgesics were also given as needed for pain control. Post-embolization hospital course was noted. RESULTS: The indications for embolization included hydronephrotic, poorly functioning kidneys with pain in 5 cases, and recurrent bleeding from angiomyolipoma, bleeding after percutaneous resection of renal pelvic transitional cell carcinoma with metastases and spontaneous renal bleeding after hemodialysis in 1 each. Embolization was successful in 4 men and 4 women with a mean age of 58.8 years. In 6 patients severe flank pain required narcotic analgesics. One patient complained of nausea, 6 had fever and 6 had leukocytosis. In 1 case thrombosis of a limb of an aortobifemoral bypass graft required thrombectomy. Median hospital stay was 2.5 days. At a mean followup of 30.6 months presenting symptoms had resolved in all cases without hypertension, renal failure or abscess. CONCLUSIONS: Complete renal embolization is a viable alternative to nephrectomy in patients with poorly functioning kidneys who present with pain or bleeding and in those who are poor operative candidates. This procedure is safe, reliable and minimally invasive with few long-term sequelae, and it is well tolerated.

Benign adenomatous multicystic kidney tumor (Perlmann's tumor) and renal cortical carcinoma with adenomatous multicystic features: 12 cases.

OBJECTIVES: To re-examine clear cell cystic lesions of the kidney and to assess their potential clinicopathologic significance, as the long-forgotten diagnosis of benign adenomatous multicystic kidney tumor (Perlmann's tumor) has not been cited in the literature in more than 35 years. METHODS: We identified 12 patients between 1959 and 1996 who underwent a radical nephrectomy at our institution and were diagnosed with either adenomatous multicystic clear cell kidney tumor (n = 4) or with renal cell carcinoma (RCC) associated with features of adenomatous clear cell multicystic kidney tumors (n = 8). All diagnoses were reviewed histologically by a single pathologist. RESULTS: Nine of 1 2 patients had Stage T2NOMO disease, and 3 patients had Stage T1 NOMO disease. There were 8 men and 4 women. The average age at the time of surgery was 60.5 years (range 25 to 74). Six patients are still alive with a mean follow-up of 4.7 years (range 1.5 to 16.3) and have no evidence of recurrent disease. Of the 6 patients who died, mean survival time was 8.8 years (range 0 to 15.7). One patient died in the perioperative period, and the other 5 patients died of other causes, unrelated to their kidney tumor. CONCLUSIONS: Adenomatous clear cell multicystic kidney disease may represent a histologically distinct benign neoplasm, and its presence in association with RCC may confer a more favorable prognosis. Its distinction from usual solid hemorrhagic or focally necrotic RCC is important.

Endopyelotomy failure is associated with reduced transforming growth factor-beta.

PURPOSE: Approximately 15% of patients with ureteropelvic junction obstruction have endopyelotomy failure and require an additional surgical procedure to remove the obstruction. Transforming growth factor-beta (TGF-beta), a cytokine which stimulates mesenchymal cell proliferation and extracellular matrix deposition, increases in the renal pelvis in response to obstruction. However, TGF-beta also is implicated in smooth muscle regeneration and wound healing. To understand the pathophysiology of ureteropelvic junction obstruction and determine why endopyelotomy fails in some obstructed ureteropelvic junctions, TGF-beta expression in obstructed and normal ureteropelvic junction segments was compared. MATERIALS AND METHODS: Immunohistochemical staining using a rabbit polyclonal anti-TGF-beta was performed on deparafinfized 4 microm. sections of paraffin blocked ureteropelvic junction segments. Human obstructed ureteropelvic junction segments were removed during primary pyeloplasties (11) and secondary pyeloplasties after endopyelotomy failure (11). Normal ureteropelvic junction segments were removed during nephrectomy for purposes unrelated to obstruction (11). Grading on a scale of 0 to 4 was performed by a physician blinded to the source of the specimen. RESULTS: Mean TGF-beta expression plus or minus standard error of the mean was significantly increased (p <0.02) in obstructed ureteropelvic junctions from primary pyeloplasties (2.6+/-0.7) compared to normal ureteropelvic junctions (1.6+/-0.7), as expected. However, TGF-beta expression in the endopyelotomy failure group (1.8+/-0.6) was not significantly different from that in normal ureteropelvic junctions and was significantly lower (p <0.05) than that in obstructed ureteropelvic junctions from primary pyeloplasties. CONCLUSIONS: Obstructed ureteropelvic junctions in cases of endopyelotomy failure have decreased expression of TGF-beta compared with other obstructed ureteropelvic junctions. These data suggest that an elevation of TGF-beta in obstructed ureteropelvic junctions may be necessary for successful tissue repair after endopyelotomy.

Percutaneous removal of stone from caliceal diverticulum in patient with nephroptosis.

A novel method is introduced for percutaneous stone extraction from a lower pole caliceal diverticulum in a patient with nephroptosis, also known as a floating kidney. The patient was fully recovered and asymptomatic at 2 months postoperatively with her kidney fixed in the flank position.

Necrosis of the urethra and tissue sloughing: a delayed complication after transurethral microwave thermotherapy.

Transurethral microwave thermotherapy is a minimally invasive treatment for benign prostatic hyperplasia designed to destroy hyperplastic tissue without damaging the urethra. We present an unexpected complication of prostatic urethral necrosis and tissue sloughing after thermotherapy and discuss its possible cause.

The in vitro bactericidal effect of microwave energy on bacteria that cause prostatitis.

OBJECTIVES: We investigated the in vitro nonthermal effects of microwaves delivered from Prostatron 2.0 on Escherichia coli and Enterobacter cloacae. METHODS: The fingers of powder-free, sterile gloves were ligated, and bacterial solutions were transferred into the remaining area of the glove. The gloves were then sealed using silk ligatures. One set of gloves was subjected to the microwave treatment while another set was placed in a temperature-matched waterbath to act as control samples. The gloves containing the treatment group were taped around the probe, at the site where microwave energy exits the probe. During the treatment period, the temperatures from the urethral probe and the rectal probe were carefully monitored. RESULTS: The mean (+/-SD) energy delivered was 46.6 +/- 9.5 kJ (range 30.0 to 59.5) for the 10 trials on E. coli and colony counts in the experimental microwaved gloves decreased significantly compared with control samples (5.26 +/- 4.5 x 10(5) versus 10.16 +/- 9.3 x 10(5) CFU/mL, P = 0.02). For the experiments on E. cloacae the mean (+/-SD) energy applied was 38.5 +/- 12.5 kJ, and a significant decrease in colony counts of microwaved samples was also observed compared with controls (11.04 +/- 4.8 x 10(5) versus 20.08 +/- 10.1 x 10(5) CFU/mL, P = 0.004). CONCLUSIONS: Microwave energy, delivered from Prostatron 2.0, independent of heat production has an in vitro bactericidal effect on laboratory-cultured E. coli and E. cloacae.

Endopyelotomy after failed pyeloplasty: the long-term results.

PURPOSE: Endopyelotomy has been proposed as a technique to treat ureteropelvic junction obstruction after failed open pyeloplasty. However, to our knowledge no long-term results of this treatment have been reported. We report the long-term followup of a cohort of patients in whom pyeloplasty failed and who subsequently were treated with endopyelotomy. MATERIALS AND METHODS: From January 1985 to February 1996, 72 patients in whom open surgical pyeloplasty failed were treated with percutaneous endopyelotomy. Mean patient age was 35 years (range 5 to 82). The interval between pyeloplasty and subsequent failure ranged from 2 months to 30 years (mean 57 months). The major presenting symptoms were pain in 82% of cases, fever and urinary tract infections in 37.5%, stone formation in 25% and gross hematuria in 21%. RESULTS: Antegrade endopyelotomy using a hooked knife was performed in all patients with no unusual difficulty and minimal complications. A total of 63 patients (87.5%) had long lasting clinical and radiographic treatment success after a mean followup of 88.5 months. Of the 9 endopyelotomy failures (12.5%) 7 (77.8%) were detected immediately after stent removal at 6 weeks, 1 (11.1%) at 6 months and 1 (11.1%) at 10 months postoperatively (mean failure interval 3.3 months). The failures were corrected with repeat endopyelotomy in 1 patient, pyeloplasty in 3, ileal interposition in 1 and nephrectomy in 4. CONCLUSIONS: Endopyelotomy is the treatment of choice for recurrent ureteropelvic junction obstruction after failed pyeloplasty, with a high and sustained long-term success rate and no reported new failures after 1-year followup. Furthermore, endopyelotomy is technically easier with less morbidity than repeat open pyeloplasty.

Endopyelotomy for horseshoe and ectopic kidneys.

PURPOSE: We report our experience with endopyelotomy for horseshoe and ectopic kidneys in the largest series to date to our knowledge, and discuss the technical modifications adopted to perform successfully percutaneous antegrade endopyelotomy. MATERIALS AND METHODS: From September 1987 to April 1996, 4 patients with horseshoe and 5 with ectopic kidney underwent percutaneous antegrade endopyelotomy for symptomatic ureteropelvic junction obstruction. The percutaneous puncture was made more posteromedial and the ureteropelvic junction was incised lateral. A retrograde percutaneous access tract was created under laparoscopic guidance in pelvic kidneys. RESULTS: The operative procedure was performed uneventfully in all patients with no major bleeding, pleural effusion or visceral perforation. The stents were removed at 6 weeks, and an excretory urogram was performed at 2 weeks, 6 months and yearly thereafter. In 2 patients (22%) with severe hydronephrosis, poor renal function and a long ureteral stricture surgical treatment failed immediately. The remaining 7 patients (78%) had long lasting clinical and radiographic success with a mean followup of 62 months. CONCLUSIONS: Percutaneous antegrade endopyelotomy, with a few technical modifications, is a safe and effective treatment for ureteropelvic junction obstruction associated with horseshoe and ectopic kidneys.

Transurethral microwave thermotherapy for management of benign prostatic hyperplasia: a single-institution experience.

OBJECTIVES: This is the first and largest single institution retrospective study in the United States to examine the effects of transurethral microwave thermotherapy (TUMT) for the treatment of benign prostatic hyperplasia (BPH). METHODS: From September 1996 to June 1997, 78 men with moderate to severe symptomatic BPH were treated with the Prostatron at our institution. Patient age ranged from 52 to 85 years. Prostate volume ranged from 23 to 110 cc, and mean total energy applied during the treatment was 156.17 kJ. Patients were re-evaluated at 3 months and were asked to answer a questionnaire regarding their opinion about the treatment. RESULTS: At 3 months there was a significant decrease in mean symptom score from 19.6 to 11.2 (P <0.0001). Mean peak flow rate increased from 8.5 to 12.8 mLs (P <0.0001). Mean postvoid residual urine decreased from 56.8 to 22.0 mL (P <0.0001). We did not observe any severe complications. Unlike prior studies, we removed the Foley catheter, and patients performed clean intermittent catheterization (CIC) when necessary. There was no significant differences in subjective and objective parameters between these patients and those who did not need CIC. Patient opinion about the treatment was not affected by CIC. About two thirds (67.2%) of the patients in the study group were satisfied with the results of treatment, and 60.3% would undergo the same procedure again. CONCLUSIONS: TUMT of the prostate is an effective, safe, and acceptable form of treatment for patients with BPH. Longer follow-up is needed to examine the durability of TUMT treatment.

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.

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.