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Purpose: Interstitial cystitis is a painful bladder condition of unknown etiology and poorly understood pathophysiology. Current therapies have met with limited success. Vanilloid receptor agonists such as resiniferatoxin (RTX) desensitize C-fibers that transmit pain; it is hypothesized that such drugs will be effective in the treatment of interstitial cystitis and painful bladder syndrome by decreasing the pain that leads to urinary frequency and urgency., Materials and Methods: A randomized, double-blind, placebo controlled study was conducted in 163 patients with interstitial cystitis. Participants were randomly assigned to receive a single intravesical dose of 50 ml of either RTX 0.01 microM, 0.05 microM, 0.10 microM, or placebo. Safety and efficacy was evaluated over 12 weeks. The primary efficacy endpoint was the Global Response Assessment, a 7-point scale rating overall change in symptoms of interstitial cystitis after 4 weeks. Secondary efficacy endpoints included reduction in pain, urgency, frequency, nocturia, average void volume, and the O'Leary-Sant Symptom and Problem Indexes., Results: RTX did not improve overall symptoms, pain, urgency, frequency, nocturia, or average void volume during 12 weeks followup. RTX resulted in a dose-dependent increase in the incidence of instillation pain, but was otherwise generally well tolerated., Conclusions: In the largest prospective, randomized clinical trial reported to date with intravesical vanilloid therapy, single administration of RTX at doses of 0.01 microM to 0.10 microM was not effective in patients with interstitial cystitis.

Objectives: To compare the current recommended dose of pentosan polysulfate sodium (PPS) with doses two to three times higher., Methods: We evaluated three dosages (300, 600, and 900 mg) of PPS in a randomized, double-blind, double-dummy, parallel-group, multicenter, 32-week study. Adults (n = 380) with a diagnosis of interstitial cystitis (IC) as determined by a positive cystoscopic examination combined with bladder pain and urgency or a history of IC symptoms for at least 6 months were enrolled. Participants completed the Patient's Overall Rating of Symptom Index (PORIS) and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) at baseline (ICSI only) and during follow-up visits at 4, 8, 12, 16, 24, and 32 weeks., Results: Mean ICSI scores improved significantly during the 32 weeks for all dosages (baseline 11.2, 11.9, and 11.9 to endpoint 8.2, 8.1, 8.6 for 300, 600, and 900 mg, respectively; P <0.001) but the response to treatment was not dose dependent (no statistically significant difference in response among the three dosages). At baseline, 3.2%, 62.2%, and 34.6% reported mild, moderate, and severe symptoms, respectively, as assessed by the ICSI. At study end, 27.5%, 56.9%, and 15.7% reported mild, moderate, and severe symptoms, respectively. The PORIS scores improved within 4 weeks with 15.8% to 21.1% of all patients classified as responders (50% or greater improvement on PORIS). At 32 weeks, 49.6%, 49.6%, and 45.2% of all patients were responders at a dose of 300, 600, and 900 mg, respectively. Most adverse events were mild and resolved without intervention., Conclusions: For all three dosages of PPS, a clinically significant but similar response was demonstrated. The duration of therapy appears to be more important than the dosage.

Objectives: To evaluate further the intravesical potassium sensitivity test (PST) as an indicator of the epithelial leak of interstitial cystitis (IC) and determine whether successful pentosan polysulfate (PPS; Elmiron) treatment is associated with a change in PST results. Most individuals with IC appear to have an abnormally permeable epithelium that allows urinary solutes such as potassium to penetrate to the bladder interstitium, provoking symptoms., Methods: Data were from an optimal dose trial of PPS in IC. Patients underwent a PST before and after a 32-week trial of 300, 600, or 900 mg PPS/day. The response to PPS treatment was measured using the Patient Overall Rating of Improvement in Symptoms scale. The before and after treatment PSTs and Patient Overall Rating of Improvement of Symptoms scores were compared., Results: Of 377 patients with IC at 28 centers, 302 (80%) had a positive PST at entry. Of the 198 patients who completed the study, 153 were PST positive at entry and 92 (60%) showed clinical improvement at exit. Clinically improved patients had significant improvement on the PST analog pain and urgency scales (3.2 to 1.3 and 3.6 to 1.9, respectively; P <0.0001). In contrast, patients with no clinical improvement had no significant change in pain (3.1 to 2.7) or urgency (3.6 to 3.2)., Conclusions: PST shows abnormal epithelial permeability in most patients with IC and a significant reduction in this permeability after successful PPS therapy. PST appears to be a valid indicator of epithelial abnormality and a reliable test in the diagnosis of IC.

Percutaneous nephrostolithotomy with or without extracorporeal shock wave lithotripsy (ESWL) has been extensively used in the management of staghorn calculi, with stone-free rates varying from 23 to 86%. Explanations for the variability of such results include differences in stone burden, differences in percutaneous techniques and an overreliance on ESWL. The results and changing trends in the relative roles of percutaneous nephrostolithotomy and ESWL in the management of staghorn calculi at the Methodist Hospital of Indiana were examined. We reviewed 343 cases of staghorn calculi (partial and complete) with adequate followup data, which were managed with initial percutaneous nephrostolithotomy. Cases were divided into 2 groups: group 1 (252 cases) from 1984 to 1987 when access was performed by a radiologist and group 2 (91 cases) from 1988 to 1990 when access was performed by a urologist. Although stones in group 2 tended to be larger, a decreasing dependence on ESWL was noted (64.7% in group 1 compared to 35.2% in group 2, p less than 0.001). Despite the larger stone size in group 2, stone-free rates were similar (83.3% in group 1, 86.8% in group 2). In groups 1 and 2 percutaneous nephrostolithotomy alone achieved stone-free rates of 91% and 91.5%, respectively. The stone-free rate with the combination approach was 79.1% and 78.1% in groups 1 and 2, respectively. Technical refinements with percutaneous nephrostolithotomy in group 2 include accurate and carefully selected accesses (superior pole in 36.3%) for best approach to the stone, multiple accesses (13.3%) and improved skills in flexible nephroscopy. Blood transfusion has not been required in group 2 compared with 11.1% in group 1. Mean hospital stay was 12.4 days in group 1 and 10.3 days in group 2 (percutaneous nephrostolithotomy alone, 7.2 days). With careful attention to percutaneous nephrostolithotomy techniques, complex renal stones can be successfully managed endourologically, reducing the need for combination ESWL. Complications previously associated with percutaneous nephrostolithotomy have decreased.

Treatment recommendations and results reported for the management of staghorn calculi are highly variable. In an attempt to provide a more objective means to compare treatment results for staghorn renal calculi, stone burden as measured by stone surface area was used. Stone surface area was determined by computer analysis. A total of 380 cases of staghorn calculi treated at the same institution was evaluated. Treatment consisted of initial percutaneous nephrostolithotomy with or without extracorporeal shock wave lithotripsy (ESWL*) in 298 cases and ESWL monotherapy in 82. When considered as a group, the overall stone-free rate for initial percutaneous nephrostolithotomy (mean surface area 1,378.3 mm.2) was 84.2% compared to 51.2% (p less than 0.0001) for ESWL monotherapy (mean surface area 693.4 mm.2). For staghorn calculi smaller than 500 mm.2 a stone-free rate of 94.4% was achieved in the percutaneous nephrostolithotomy with or without ESWL group compared to 63.2% for ESWL monotherapy (p = 0.0214). For calculi of 501 to 1,000 mm.2 the stone-free rates were 86% and 45.7%, respectively (p less than 0.0001). When stone surface area exceeded 1,000 mm.2 the stone-free rate for percutaneous nephrostolithotomy with or without ESWL was 82.4% but it was only 22.2% for ESWL monotherapy (p = 0.0002). Overall, when adjusted for stone surface area the odds of being stone-free were more than 8 times higher for initial percutaneous nephrostolithotomy versus ESWL monotherapy (odds ratio = 8.36, p less than 0.0001). While percutaneous nephrostolithotomy with or without ESWL appears to be the procedure of choice for most staghorn stones, ESWL monotherapy may have a role for some stones smaller than 500 mm.2. In 12 such cases associated with a nondilated renal collecting system (mean surface area 380.5 mm.2) a stone-free rate of 91.7% was achieved. The number of procedures required to complete therapy was higher in the initial percutaneous nephrostolithotomy group (2.8 versus 2.1, p less than 0.0001). Although complications were more common in the ESWL monotherapy group (manifested as obstruction in 30.5%), bleeding requiring blood transfusion was more frequent in the initial percutaneous nephrostolithotomy group (9.4%).

Extracorporeal shock wave lithotripsy treatment for calculi of the upper urinary tract was performed in 15 children between 3 and 17 years old. Success was achieved in 93 per cent of the cases (72 per cent were free of stone and 21 per cent had insignificant fragments). No major complications were encountered in the series.

There were 98 patients with a variety of intrascrotal lesions studied with a radioisotope 99mtechnetium-pertechnetate scanning technique. Retrospective analysis in 50 patients subjected to an operation revealed a 94 per cent accuracy of the scan in the differential diagnosis of testicular torsion and epididymitis as compared to a clinical accuracy of 48 per cent. In 7 patients with a scan diagnosis of epididymo-orchitis with abscess the diagnosis was confirmed during the operation or by followup examination. While the scan has been a simple, safe, rapid and reliable technique to differentiate acute and subacute lesions, it has proved to be of limited diagnostic significance in cases of chronic intrascrotal lesions and carcinoma.

Two new therapies, percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy, are revolutionizing the treatment of upper urinary tract calculi. We report the success and morbidity rates in 110 patients undergoing percutaneous nephrostolithotomy and 982 patients treated with extracorporeal shock wave lithotripsy. Staghorn calculi were excluded from this series. The over-all success rate (free of stones plus small asymptomatic residual fragments) was comparable with both modalities (percutaneous nephrostolithotomy 98 per cent and extracorporeal shock wave lithotripsy 95 per cent), although the presence of residual fragments was more common in kidneys treated with extracorporeal shock wave lithotripsy (24 versus 7 per cent). Patient morbidity as measured by temperature elevation, length of postoperative stay, pain and blood loss was significantly less (p less than 0.05) with extracorporeal shock wave lithotripsy than with percutaneous nephrostolithotomy. Re-treatment rates were similar with both procedures, and tended to increase in relation to increasing stone size and stone number. Post-treatment ancillary procedures (cystoscopy and stone manipulation, and percutaneous nephrostomy) were used more frequently with extracorporeal shock wave lithotripsy. Because of its efficacy and low morbidity, we conclude that extracorporeal shock wave lithotripsy is the treatment of choice for upper urinary tract calculi less than 2 cm. in diameter. However, percutaneous nephrostolithotomy will continue to have a primary role in the management of larger stones and cystine stones, and it will be used as a secondary procedure after unsuccessful extracorporeal shock wave lithotripsy treatments. In addition, because of the complimentary nature of these 2 new technologies certain complex stones, such as staghorn calculi, may be handled best by a combination of the 2 techniques.

The results of 471 extracorporeal shock wave lithotripsy treatments in 465 patients with solitary ureteral stones managed by several different techniques are reported. In situ treatment was performed in 123 cases without instrumentation and in 47 after placement of a ureteral catheter. Retrograde stone manipulation was performed in 245 cases immediately before extracorporeal shock wave lithotripsy and an additional 56 were manipulated with ureteral stent placement at least 1 week before extracorporeal shock wave lithotripsy. The success rate was significantly greater if the stone was manipulated into the kidney before extracorporeal shock wave lithotripsy. Significantly less energy (p less than 0.0001) was required for complete disintegration if the stone was free floating in the kidney. The need for subsequent procedures was significantly less (p less than 0.0001) for stones manipulated successfully into the kidney. Complications were infrequent, with the most common being ureteral perforation in 5.1 per cent of the cases, all of which were managed conservatively. Extracorporeal shock wave lithotripsy is the treatment of choice for proximal ureteral calculi because it is less morbid than percutaneous approaches and provides significantly better results than ureteroscopy. An attempt at manipulation of proximal ureteral calculi back into the kidney should be made before extracorporeal shock wave lithotripsy.

Subcapsular or perirenal bleeding is the most commonly experienced adverse effect directly attributable to externally applied shock waves. The first consecutive 3,620 extracorporeal shock wave lithotripsy treatments with the HM3 Dornier lithotriptor at our institution resulted in 24 hematomas in 21 patients, for an incidence of 0.66 per cent. Various factors associated with treatment were examined. The number of shock waves (up to 2,000) and voltage up to 24 kv. did not correlate with the development of hematoma. Coagulation studies were normal in all patients with hematomas. There was no correlation of patients size and weight, or stone size, number or location with the occurrence rate of perinephric hematoma. Patients with pre-existing hypertension, particularly those with unsatisfactory control of hypertension, had a significantly increased incidence of perinephric hematoma. The incidence of hematoma in hypertensive patients was 2.5 per cent and it increased to 3.8 per cent in patients with unsatisfactory control of hypertension. Therefore, pre-existing hypertension is a significant risk factor in the occurrence of post-extracorporeal shock wave lithotripsy bleeding. The incidence of perinephric hematoma also was increased in patients with pre-treatment urinary tract infection and those who underwent simultaneous bilateral treatment. Management of post-extracorporeal shock wave lithotripsy bleeding generally is conservative although a third of the patients required transfusion.

Combinations of percutaneous and extracorporeal shock wave lithotripsy were performed on 46 patients with 52 staghorn calculi. Of the renal units 15 per cent had minute residual fragments but only 9.7 per cent with struvite had residual stones. The morbidity of this combined approach is less than that of anatrophic nephrolithotomy. We believe that the majority of staghorn calculi can be removed in this manner. Nephrostolithotomy should be the initial procedure in most instances. This less invasive approach is especially advantageous in patients at high risk for recurrence.

Extracorporeal shock wave lithotripsy was used to treat 68 patients with renal calculi in a solitary kidney. Epidemiological information, including stone number, size and location, was similar to that of other patients treated with extracorporeal shock wave lithotripsy. Renal function as measured by serum creatinine changed negligibly in the majority of the patients. Three patients had transient serum creatinine elevations greater than 2 mg. per dl. that were caused by obstruction from stone fragments. There were 2 perirenal hematomas that required transfusion. One patient required retrograde manipulation of a ureteral stone before extracorporeal shock wave lithotripsy, while 6 required stone manipulations after therapy for steinstrasses. Of 59 patients evaluable after extracorporeal shock wave lithotripsy 58 (98.3 per cent) had a successful result: 38 (64.4 per cent) were completely free of stones and 20 (33.9 per cent) had clinically insignificant residual fragments. Extracorporeal shock wave lithotripsy is effective and safe in a solitary renal unit. We believe that in most patients it is the procedure of choice. Attention to fever, urine output and fragment size perioperatively is crucial.

A total of 206 procedures was performed on 193 patients with ureteral calculi. The success rate was 62 per cent for stones proximal to the pelvic brim and 94 per cent for stones distal to the pelvic brim (87 per cent success over-all). Of the procedures 61 were done for fragments lodged in the ureter following extracorporeal shock wave lithotripsy. Ureteroscopy was done in 147 cases. Our current management concepts (including extracorporeal shock wave lithotripsy) for proximal and distal ureteral calculi are presented.

A total of 982 patients underwent 1,416 treatments with extracorporeal shock wave lithotripsy for upper urinary tract calculi between February 23 and December 17, 1984. A single treatment was performed in 90 per cent of the patients. Morbidity was extremely low and hospital stay was short (3.0 days). Adjunctive procedures were required in 13 per cent of the patients. Of the kidneys 72 per cent were free of stones at the 3-month followup, while 23 per cent contained small (less than 5 mm.), asymptomatic fragments believed to be passable spontaneously. Only 1 per cent of the patients required surgical removal of the calculi. Morbidity was related directly to stone burden, while results were inversely related to stone burden. Extracorporeal shock wave lithotripsy is the preferred form of management for symptomatic upper ureteral and renal calculi less than 2 cm. in diameter.

Analysis of our data clearly demonstrates that morbidity, secondary treatment, post-treatment manipulations, and failure of treatment increase as the stone size increases because of the increased stone fragment burden. Patients whose stone burden was less than 2 cm clearly had less morbidity. Composition of the stone may also alter the success of treatment (with cystine, calcium oxalate monohydrate, and brushite stones being resistant to treatment). However, post-treatment morbidity and complications were observed in all categories. Perirenal hematomas are unpredictable by current preoperative testing. Obstruction with pain can occur any time after treatment but usually occurs within the first 48 hours in the majority of patients. Only 1 per cent of our patients required hospitalization in another institution after discharge. Ambulatory ESWL requires that staff at the facility or a urologist be able to observe and appropriately follow the patient for 24 to 48 hours after treatment.