Innovative Approach for Interstitial Cystitis: Vaginal Pessaries Loaded Diazepam-A Preliminary Study.

Bladder pain is a characteristic disorder of interstitial cystitis. Diazepam is well known for its antispasmodic activity in the treatment of muscular hypertonus. The aim of this work was to develop and characterize vaginal pessaries as an intravaginal delivery system of diazepam for the treatment of interstitial cystitis. In particular, the performance of two types of formulations, with and without beta-glucan, was compared. In particular, the preparation of pessaries, according to the modified Pharmacopeia protocol, the setup of the analytical method to determine diazepam, pH evaluation, dissolution profile, and photostability assay were reported. Results showed that the modified protocol permitted obtaining optimal vaginal pessaries, without air bubbles, with good consistency and handling and with good pH profiles. In order to determine the diazepam amount, calibration curves with good correlation coefficients were obtained, by the spectrophotometric method, using placebo pessaries as matrix with the addition of diazepam standard solution. This method was demonstrated sensible and accurate to determine the amount of drug in batches. Dissolution profiles showed a complete diazepam release just after 15 minutes, even if beta-glucan pessaries released drug more gradually. Finally, a possible drug photodegradation after exacerbated UV-visible exposition was evaluated.

Results of endovesical hyaluronic acid/chondroitin sulfate in the treatment of Interstitial Cystitis/Painful Bladder Syndrome.

OBJECTIVES: The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients. METHODS: A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response. RESULTS: After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks' treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement. CONCLUSIONS: In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.

A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis.

The aims of this study were to evaluate the efficacy and tolerability of intravesical instillations of high-molecular-weight hyaluronic acid (HA) 1.6% and chondroitin sulfate (CS) 2.0% in patients with refractory painful bladder syndrome/interstitial cystitis (PBS/IC) and to observe their impact on Quality of Life. Twenty-three women were enrolled. They received bladder instillations with HA and CS weekly for 20 weeks and then monthly for 3 months. Mean follow-up after completion of therapy was 5 months. We observed a significant improvement in urinary symptoms on voiding diaries and Visual Analogue Scale for frequency (p = 0.045), urgency (p = 0.005), and pain (p = 0.001). The O'Leary-Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index resulted in a significant improvement in both scores (p = 0.004 and 0.01, respectively). The Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant improvement in the symptom score (p = 0.001). This promising experience seems to offer an additional therapeutic option in patients with refractory PBS/IC.

Home and office uroflowmetry for evaluation of LUTS from benign prostatic enlargement.

A group of 107 patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE) participated to the HOUSE Study (Home and Office Uroflowmetry Specific Evaluation). Patients received routine investigation, consisting of medical history taking, physical examination including digital rectal examination, prostate-specific antigen (PSA), assessment of symptoms listed both on the International Prostate Symptom Score and on ICS-male questionnaire. We examined the results of uroflowmetry evaluation in this population; data were analysed to observe if any circadian changes of parameters obtained with home uroflowmetry could be detected. We searched a correlation between Q(max), Q(ave) and ICS-benign prostatic hyperplasia symptom score: a significantly inverse correlation was found only for Q(max), confirming Q(max) as a reliable parameter to quantify subjective symptoms. When examining the multiple flow curves recorded in the same patient with home uroflowmetry, voided volume and flow time had usually higher values during night-time: the existence of circadian changes of uroflowmetry parameters in patients with LUTS from BPE was confirmed, and lower values of average and maximum flow rates during sleep hours were recorded in the same patient. In conclusion, when evaluating the natural history or treatment outcome of individual patients or group of patients in clinical trials for evaluation of BPE and LUTS, an assessment including multiple measurements may be useful and of value.

Bilateral ureteral compression by multiple abdominal desmoid tumors in Gardner syndrome: case report and literature review.

A 28-year-old man with Gardner syndrome was admitted to our Department because of multiple abdominal masses. Abdominal computed tomography revealed severe hydronephrosis of both kidneys due to ureteral compression against the pelvic bones exerted by multiple solid abdominal masses. The patient developed oligoanuria. Right percutaneous nephrostomy tube placement was followed by restoration of diuresis and progressive recovery of renal function of the left side. The patient then underwent median laparotomy and removal of five large desmoid tumors originating from the abdominal wall. Bilateral ureteral obstruction due to abdominal desmoid tumors can be a rare urologic complication of Gardner syndrome.

Different clinical presentation of interstitial cystitis syndrome.

The aim of the study was to examine how interstitial cystitis (IC) initiates its clinical course, which changes as the disease progresses from the initial phase to its full clinical manifestation. Patients diagnosed with IC between 1998 and 2003 in our department were evaluated and reviewed regularly. The exact onset of urinary symptoms was recorded. Diagnosis of IC was made by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria when clinical suspicion of IC was present. The study group included 30 female patients who were 27-69 years old when diagnosis was made. Mean age was 46.7. Seventy percent of patients had only one symptom at onset. The most frequent initial diagnosis was urinary tract infection (UTI). A condition of recurrent bacterial UTIs, with subsequent persistence of symptoms and negative cultures, could be detected as a harbinger of IC in 60% of our patient group. IC may manifest initially with a single symptom in its early stage, when diagnosis is perhaps less easy, but adequate and effective treatment can still be offered to the patient.

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.

Prognostic value of a combination of IPSS, flow rate and residual urine volume compared to pressure-flow studies in the preoperative evaluation of symptomatic BPH.

OBJECTIVE: Evaluate the predictive value of a combination of IPSS, uroflowmetry and ultrasound determination of residual urine volume in the determination of bladder outflow obstruction (BOO) and in predicting treatment outcome. METHODS: Forty-five out of a group of 60 BPH symptomatic patients were included. Preoperative evaluation: urine culture, PSA, uroflowmetry with sonographic measurement of post-void residual urine, DRE, IPSS with quality of life questions and pressure-flow study. Selection criteria for surgery were IPSS > 16 and Qmax < 10 ml/s. Transurethral resection of the prostate was performed in these patients; the control visit was performed at 3 months. Treatment success was defined as Qmax above 15 ml/s, residual urine of less than 100 ml, a 50% reduction in IPSS and absence of urinary retention. RESULTS: Urodynamic abnormalities were found in 42 patients (93.3%): 19 had detrusor instability, 5 patients showed impaired contractility, 37 patients had proven BOO, and 8 patients were unobstructed or mildly obstructed. The overall success rate was 86% when measured by the IPSS. Its preoperative value was 16.9, and dropped significantly to 4 (P = 0.005). The score improved significantly after surgery only in the obstructed group compared to the non-obstructed group (P = 0.001), however preoperative IPSS did not correlate with objective treatment results. CONCLUSIONS: A high proportion of patients successfully operated (71.1%) had a combination of IPSS > 16 and Qmax < 10 ml/s, although BOO could not be accurately predicted with non-invasive methods alone. Patients with no or mild infravesical obstruction had only minimal improvement of IPSS and uroflowmetry following surgery.

Relationship of flow rate with symptoms, quality of life and other clinical parameters in patients with LUTS suggestive of BPH.

AIM: The uroflowmetry data of a selected number of patients who took part to the QUIBUS study (366 traces selected after quality control by a central panel of reviewer) were evaluated for their relationships with age, prostate volume, and IPSS and ICS-BPH scores. Waiting time, flow time, voided volume, maximum flow rate (Q(max)) and average flow rate (Q(ave)) were the flow variables considered for analysis. Only measurements with total voided volume exceeding 100 ml were included. RESULTS: An increasing percentage of subjects with voided volume <200 ml was observed over 65 years of age. Age did not affect neither Q(ave) nor Q(max )(p = n.s. at correlation analysis). In particular, Q(max)was <15 ml/s in about 70% of patients independently of age. Prostate enlargement was inversely associated with voided volume, Q(max) and Q(ave), showing a worsening of urinary function for increasing values of prostate volume Q(max) was negatively correlated with IPSS total score and with most single items with the exception of two storage symptoms such as repeated urination and nocturia). Accordingly, Q(max) was inversely associated with the total score ICS-BPH for voiding symptoms to a higher extent (r = -0.31, p < 0.01) than with the one for storage symptoms (r = -0.22, p < 0.01). Flow variables were inversely correlated with IPSS-QoL. CONCLUSION: Uroflowmetry and IPSS, although not allowing a definitive diagnosis of obstruction, may nonetheless satisfy the clinical need of a rapid, easy and accurate tool for the noninvasive screening of LUTS patients.

Impact of early pelvic floor rehabilitation after transurethral resection of the prostate.

We examined the results of teaching pelvic floor muscle exercises (PME) on micturition parameters, urinary incontinence, post-micturition dribbling, and quality of life in patients after transurethral prostatectomy (TURP). Fifty-eight consecutive patients who were selected to undergo TURP for benign prostatic hyperplasia (BPH) were admitted into the study: 28 were randomly assigned to a control group (A), 30 formed the investigational group (B) during an initial visit conducted before surgery. In group B patients, perineal exercises were demonstrated in detail, and tested for their correct use via simultaneous rectal and abdominal examination. After the removal of the urethral catheter, these patients were instructed to perform pelvic floor muscle exercises at home and were evaluated before the exercises and at weekly intervals postoperatively. The American Urological Association Symptom Score improved significantly after TURP in both groups. The average quality of life score improved more significantly in group B after TURP, from 5.5 to 1.5 (P < 0.001). The grade of muscle contraction strength after 4 weeks of PME increased from 2.8 to 3.8 in group B (P < 0.01); it was unchanged in the group A. The number of patients with incontinence episodes and post-micturition dribbling was significantly lower in the group B at weeks 1, 2, and 3 (P < 0.01). Our results show that pelvic floor muscle re-education produces a quicker improvement of urinary symptoms and of quality of life in patients after TURP. Its early practice reduces urinary incontinence and post-micturition dribbling in the first postoperative weeks. The exercises are simple and easy to perform in the clinical setting and at home, and therefore should be recommended to all cooperative patients after TURP.

Large benign prostatic hyperplasia means impossible ureteroscopy: myth or reality?

OBJECTIVE: We intended to ascertain the true role played by large-size prostatic glands with BPH in impeding ureteroscopy; since no such impediment was experienced by the authors, we then listed the most frequent obstacles to ureteroscopy, contrary to what is commonly reported in literature. MATERIALS AND METHODS: Endourological reports on a series of 2,147 diagnostic or therapeutic ureteroscopies were examined, together with the patients' clinical records. Male patients accounted for 1,288 cases. In 45 cases, the operators found the prostate so enlarged as to be worthy of note. In 9 of these cases, the procedure was performed bilaterally; thus, a total of 54 ureteroscopies was undertaken in patients with enlarged prostates or large median lobes. RESULTS: None of the surgical reports indicated that the ureteroscopic procedure was hindered by an enlarged prostate. On the other hand, the most frequent causes preventing ureteroscopy are, for both male and female patients, some types of tumor: uterine, ovarian, ureteral, bowel, bladder and prostate cancer, and inflammation. CONCLUSIONS: Benign prostatic hypertrophy (BPH) is not of itself an impediment to ureteroscopy when it is performed by an expert operator equipped with suitable instruments. On the other hand, tumours of the female reproductive system, as well as bladder and prostate tumours and serious inflammations and infections may make the procedure impossible or cause serious problems during its performance, at times requiring combined antegrade and retrograde maneuverings. At the root of this obstacle lies neoplastic or inflammatory infiltration and stiffening which attaches itself to the organs and hardens their connections. In the case of BPH, we do not find infiltration, but only a dislocation, which can be compensated by means of a few technical stratagems. Some interesting expedients in the incannulation of difficult meatuses were already suggested in 1914 by Heitz-Boyer and Marion.

Urodynamic analysis of voiding dysfunction in orthotopic ileal neobladder.

We examined the urodynamics, particularly voiding dysfunction, in patients with a neobladder. Free uroflowmetry, pressure-flow study, and voiding cystourethrography were performed in 22 patients (mean age 65 years) at a mean of 21 months after ileal neobladder substitution. The results of free uroflowmetry were used to divide patients into two groups: the good voiders and the poor. Daytime continence was achieved in all patients, while 10 (45%) had nighttime continence. To void 250 ml urine the good voiders strained 2 +/- 1.5 times, and the poor voiders 6 +/- 5 times. The neobladder neck was at the most caudal portion of the reservoir in good voiders, and there was wide funneling. In the group with poor emptying ability, the outlet was not located at the most dependent position. The principal factors for ensuring good voiding function in neobladder patients are the ability to perform effective straining and the location of the neobladder neck.

Evaluation of morbidity of multi-channel pressure-flow studies.

This prospective study was carried out to evaluate the morbidity and complication rate of invasive urodynamics of the lower urinary tract after receiving oral antibiotic prophylactic treatment. A total of 105 patients, 55 men and 50 women, were included in the study and underwent pressure flow study (PFS) as part of the diagnostic assessment. Clinical diagnosis was prostatic obstruction from benign prostatic hyperplasia (BPH) in men and stress urinary incontinence or voiding dysfunction in women. Urine was screened for infection both before and after testing, and the incidence of urinary tract infections (UTI), dysuria, and other complications were assessed at 1-week follow-up to evaluate post-investigation morbidity. Dysuria of mild degree was experienced by 33% of patients, with no significant difference between male and female patients. Post-investigational UTI and fever were reported in 3.6% of men and 4% of women. Six patients had macroscopic hematuria of mild degree. No patient had urinary retention or severe complaints after the investigation and no patient required hospitalization. Post-void residual volume was higher in men with BPH obstruction compared to women; a significant difference between post-investigational UTI and residual volume could not be demonstrated (P = 0.8). We conclude that the objective morbidity rate of invasive urodynamic investigation is low. Mild dysuria is common, while severe complications, fever, and hematuria are seldom reported, and the risk of developing UTIs is low with antibiotic prophylaxis, with no significant difference between men and women. Neurourol. Urodynam. 18:647-652, 1999.

[Temporary retrograde and anterograde ureteral catheterization]. / Sondage urétéral temporaire rétrograde et antérograde.

This article examines the technical modalities or ureteral catheterization. The authors also discuss unconventional modalities which, if used without prejudice, can sometimes constitute brilliant and economic solutions to complex problems which are often impossible to resolve otherwise. After a summary of the history of ureteral catheterization, the authors present the main indications for temporary ureteral catheterization: radiographic and fluoroscopic examination of the ureter; separate cytological harvesting; separate bacteriological harvesting; confirmation of the side of unilateral haematuria; preliminary temporary dilatation of the ureter to prepare it for ureteroscopy; temporary drainage of the excretory tract after endourological investigation. The authors also present particular situations may be observed temporary catheterization, or even permanent stenting, for example in the case of procedures in children, pregnant women and renal transplant recipients.

The responsiveness of the ICSmale questionnaire to outcome: evidence from the ICS-'BPH' study.

OBJECTIVE: To evaluate the responsiveness of the ICSmale questionnaire to the outcome of treatments for lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Consecutive men aged >45 years attending 23 urology centres in 12 countries, with symptoms suggestive of bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), were recruited to Phase I of the International Continence Society (ICS)-'BPH' study. In Phase II of the ICS-'BPH' study, 355 men in 15 centres in nine countries were followed up, having proceeded to treatment according to clinical practice. All men completed the ICS-'BPH' study questionnaire at baseline and follow-up, including the ICSmale which concerns LUTS and related problems. RESULTS: Patients included in Phase II were similar to those in Phase I according to age and levels of baseline symptoms. Patients received a range of treatments: 32% TURP, 29% drug therapies, 20% watchful waiting, 9% minimally invasive therapies and 10% 'others' (including open prostatectomy). For patients who underwent TURP, most LUTS, including voiding and filling symptoms, were highly statistically significantly better at follow-up than at baseline (P<0.0001). For drug, minimally invasive and 'other' treatments, fewer LUTS were highly statistically significantly better. For those undergoing watchful waiting, no symptoms were significantly different between baseline and follow-up. CONCLUSION: The ICSmale questionnaire, in addition to being psychometrically valid and reliable, is responsive to change in outcome.

Holmium:YAG laser ureterolithotripsy.

OBJECTIVE: To report on the experience obtained in the treatment of a series of 150 cases of ureteral stone disease by means of the holmium:yttrium-aluminum-garnet (Ho:YAG) laser. METHODS: One hundred and fifty consecutive cases treated by means of Ho:YAG laser ureterolithotripsy have been reviewed in order to assess the results. In 81 cases the stones were located in the lower third, in 47 in the medium third, and in 22 cases in the upper third of the ureter. The laser was set at a power of 8-10 W and at a frequency of between 6 and 10 Hz. Thin ureteroscopes were selected, such as the 7-Fr Gautier or the new ultrathin 4.8-Fr Wolf instrument. In some cases other ureteroscopes were chosen. RESULTS: Lasertripsy was effective in every kind of stone, allowing fragmentation into portions measuring at most 4 mm (largest diameter) or disintegration. The clearance rate of the stones was 92.6% during the 30-day follow-up period. Calcium dihydrate stones were of course more easily broken than monohydrate ones. No damage to the ureter was observed following the vaporization which is produced by this kind of laser, since particular attention was paid to avoid any contact between the laser beam and the ureteral mucosa. In some instances ureteroscopic maneuvering provoked some slight lacerations. In a few cases accidental contact of the laser beam with the ureteral mucosa produced extremely small coagulations of no immediate or postoperative relevance. CONCLUSIONS: The Ho:YAG laser constitutes an effective instrument for the fragmentation of any kind of ureteral stone; it allows the use of thin or ultrathin instruments and, if manipulated with care, does not damage the ureteral mucosa or the ureteral wall.

Urinary symptoms in women with gynecological disorders: the role of symptom evaluation and home uroflowmetry.

OBJECTIVE: The aim of our study was to analyze the effect of gynecological dysfunction on voiding symptoms in women. METHODS: A modified AUA symptom index questionnaire was self-administered and an ambulatory home uroflowmetry was performed, using a specially designed home uroflowmetry apparatus for multiple flow measurements. Urinary symptoms and home uroflowmetry (Home Urodata TM System) were evaluated in 68 women: 34 patients with gynecological dysfunction, and 34 normal controls. A total of 156 urination episodes was recorded, with a mean of 5.4 measurements per patient. RESULTS: Symptom index showed lower values in the group of normal controls than in the group with gynecological dysfunction. Voided volume, peak flow rate and average flow rate were all significantly better in the group of normal controls than in the group with gynecological disorders; the most remarkable changes were observed in patients with genital prolapse and with large uterine fibroma. In both groups the total urine volume was lower between midnight and 8 a.m. (2460 ml), if compared with the total urine volume between 8 a.m. and 4 p.m. (3360 ml) and the total urine volume between 4 p.m. and midnight (3072 ml) (p < 0.05). CONCLUSIONS: Noninvasive home uroflowmetry combines the information of a typical flowchart with uroflow parameters and supplies the physician with multiple consecutive voiding episodes, minimizing the environmental artifacts of the study. In our experience it was found to be useful to evaluate urinary symptoms reported by 18/34 patients (52.9%) with gynecological dysfunction. It can help to select which patients require further urodynamic investigation to improve the diagnostic accuracy and choose the correct treatment.

Transurethral electrovaporization of the prostate in benign prostatic hyperplasia. Evaluation of results using different urodynamic parameters.

We studied the obstruction-relieving capabilities of transurethral electrovaporization of the prostate (TVP) in 32 symptomatic patients with benign prostatic hyperplasia (BPH). Urodynamic studies with pressure-flow analysis were performed before and 6 months after treatment. All 32 patients showed significant improvement of both subjective and objective obstruction parameters. There were few postoperative irritative symptoms and one patient required recatheterization. In conclusion, TVP is a promising modification of performing transurethral resection of the prostate, and it is indeed capable of relieving bladder outflow obstruction.