Merete Holm-Bentzen

A Prospective Double-Blind Clinically Controlled Multicenter Trial of Sodium Pentosanpolysulfate in the Treatment of Interstitial Cystitis and Related Painful Bladder Disease

Painful bladder disease, sensory bladder disease, chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis, and, therefore, they are without any rational therapy. Pathogenetic theories concerning defects in the epithelium and/or mucous surface coat (including glycosaminoglycans) of the bladder, and theories concerning immunological disturbances predominate. Sodium pentosanpolysulfate (Elmiron) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes. We compared sodium pentosanpolysulfate versus placebo in a prospective double-blind, clinically controlled multicenter trial of 115 patients with painful bladder disease. Two protocols were used. Protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2), and protocol B included 72 patients with a painful bladder and unspecific histological findings. The patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months. Before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies. The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found. We conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease.

Painful Bladder Disease: Clinical and Pathoanatomical Differences in 115 Patients

The diagnostic criteria for interstitial cystitis considered as a subgroup of painful bladder disease (that is sensory bladder disease and chronic abacterial cystitis) are not well established. Some urologists rely on symptoms, while others rely on cystoscopic appearance or pathological findings. Among 115 patients with painful bladder disease we compared symptoms, and cystoscopic and urodynamic findings in those with and without detrusor mastocytosis (28 or more mast cells per mm.2) and attempted to elucidate possible differences between the groups. We chose the pathological anatomical criterion of detrusor mastocytosis to be diagnostic for interstitial cystitis. A total of 43 patients had detrusor mastocytosis and other pathological anatomical signs of interstitial cystitis, and 72 had no mastocytosis but the pathological diagnoses of chronic unspecific cystitis, fibrosis of the bladder, detrusor myopathy, intestinal metaplasia and normal findings. When the 2 groups of patients were compared we found no differences in regard to symptoms (pain, dysuria, frequency, nocturia and urgency), frequency of allergy and hysterectomy, duration of symptoms, petechial bleeding during cystoscopy with bladder distension and cystometric findings. The patients with mastocytosis differed from those without mastocytosis in that they were older, and had a higher frequency of hematuria, a higher frequency of a red, scarred and richly vascularized bladder at cystoscopy before distension, and a smaller cystoscopic bladder capacity. We conclude that by dividing patients with painful bladder into 2 groups according to the mast cell counts in the detrusor, certain differences in the clinical findings in the groups can be ruled out. However, in individual patients one cannot note with certainty to which pathological anatomical group the patient belongs, since great overlapping between the groups exists. Whether only patients with detrusor mastocytosis have interstitial cystitis depends on definitions and still remains an open question.

Nonobstructive Detrusor Myopathy in a Group of Patients with Chronic Abacterial Cystitis

Chronic abacterial cystitis is clinically and pathoanatomically an ill-defined condition, presenting with a variety of urologic symptoms and often nonspecific histology. A retrospective histologic analysis of bladder biopsies from 101 patients with chronic abacterial cystitis revealed degenerative changes in the detrusor muscle cells (detrusor myopathy) in 25 of them. The changes were often very severe, and even fatty replacement of muscle tissue was seen. Retrospective analysis of the symptoms, urodynamics and cystoscopic findings in these patients showed that none had haematuria, but five (all women) had had urinary retention requiring catheterization. Significant residual urine was found in nine patients, and the cystometrograms showed a shift to the right. No patient had infravesical obstruction. At cystoscopy less than half of the patients had petechial bleeding after bladder distension. The aetiology and pathogenesis of the degenerative changes are unknown, despite theoretic speculation. The authors conclude that careful histologic examination can identify different clinical types of chronic abacterial cystitis. Such studies may assist future research into the nature of the problem and also the search for more rational therapy.

Long Term Results of Superselective Sacral Nerve Resection for Motor Urge Incontinence

Eight female patients suffering from severe urge incontinence not manageable by conservative treatment were subjected to superselective sacral nerve resection in the period 1974-1977. The aim of the resection was a complete parasympathetic decentralization of the bladder. The resection was carried out according to the results of pre-operative sacral nerve blockade and per-operative electrical nerve stimulation. Post-operatively all cystometrograms were shifted to the right and four patients had bladder areflexia. At six months follow-up, three patients were continent, four were improved and one patient had an indwelling catheter for persistent retention. However, incontinence and detrusor instability returned in all the patients within one year. After seven to eight years follow-up one patient had died, two patients had had a urinary diversion operation and three had an indwelling urethral catheter. Only two patients were permanently improved. The surgical procedure was complicated by wound necrosis in one patient, by persistent dysesthesia in two and hypesthesia in three.

Pathology and Pathophysiology of Painful Bladder Diseases

Painful bladder disease is an ill-defined disease presenting with chronic cystitis symptoms, despite sterile urine. This report includes only patients with painful bladder diseases of unknown etiology and pathogenesis. We have chosen to classify these patients pathoanatomically as follows: interstitial cystitis, detrusor myopathy, chronic unspecific cystitis and eosinophilic cystitis. The pathoanatomical appearance of the four groups of patients are described in details and certain clinical differences appear between the groups. The etiology and pathogenesis to the inflammatory reactions and muscle changes found in the detrusor biopsies are unknown, but many theories exist. It is suggested that something in the urine gains access to the bladder wall and initiates the pathoanatomical changes through a defective urothelium and glycosaminoglycans layer. In the interstitial cystitis patients, the inflammatory process and mast cell degranulation might be monitored by the urinary excretion of 1,4-methyl-imidazole-acetic acid and eosinophil cationic protein. It is concluded that no specific therapy for the disease exists, since etiology and pathogenesis are still unknown and therefore future research in this field is very important.

Coecocystoplasty: An Evaluation of Operative Results

Coecocystoplasty for substituting or augmenting the bladder is a relatively common operation in the United States, but not in Scandinavia. In order to focus the attention on this voiding-preserving operation we evaluated the late postoperative results of 8 patients. Median follow-up was 5 years. Seven of the patients had symptoms from a contracted bladder and 1 patient with epispadias was undiverted from a ureteroileocutaneostomy. There were some early postoperative complications. Two patients had a revision of the coecocystoplasty, 1 patient ended up with a ureteroileocutaneostomy and 1 patient needed a nephrectomy because of a perirenal abscess. The patient with epispadias later had an artificial urinary sphincter because of persisting incontinence. At follow-up time all patients found that they had a better life than prior to operation since the invalidating symptoms from the contracted bladder had disappeared. One patient with residual urine had chronic urinary tract infection. All patients were continent at daytime, 3 patients had nocturnal incontinence. Urodynamic studies showed no infravesical obstruction and bladder capacity between 75 and 380 ml H2O. Three patients had decreased renal function. Based on our limited material we conclude that coecocystoplasty is a reasonable, though not unproblematic, treatment in patients with severe symptoms from a small contracted bladder and a therapeutical alternative in patients with a previously defunctionalised bladder and that this method should always be taken into consideration before a urinary diversion.

Partial Cystectomy for the Myogenic Decompensated Bladder with Excessive Residual Urine

Partial cystectomy was performed for myogenic decompensated bladder with excessive residual urine in 11 patients, in whom training instructions and pharmacological treatment were unsuccessful. Postoperatively, the patients were followed for 2-13 years (median 4 years). Both symptoms and residual urine were reduced permanently. Urodynamic testing had demonstrated underactive detrusor function in all. The supposed etiology was infravesical obstruction in 4, overdistension due to sensory bladder paresis in 3 and unknown in 4. Histological examination of the resected bladders showed focal degeneration of the smooth muscle cells (detrusor myopathy) in 7, transmural edema and vast deposits of collagen in 8, mastocytosis in 3 and eosinophilic cystitis in 1. In conclusion we regard partial cystectomy an alternative to clean intermittent self-catheterization in selected patients with excessive residual urine.

The Ams Artificial Urinary Sphincter on the Bulbous Urethra

An artificial sphincter with the cuff on the bulbous urethra was implanted in 29 patients with urinary incontinence. After a median observation time of 3 years, 19 patients were continent, four others were improved and the system had been removed in six cases. Urethral erosion occurred in only two cases, both due to infection. Use of low-pressure systems is recommended.

Medial Fibroplasia: Involvement of Renal Artery and Small Renal Arteries in Renal Vascular Hypertension

Dysplasia of the renal artery may cause renal vascular hypertension. The most common type of dysplasia is the medial fibroplasia. Medial fibroplasia, as well as the other types of dysplasia, has only been described in the main and primary branches of the renal artery. A case of medial fibroplasia, where arterial changes were seen far out in the small renal vessels is reported.

The Danish Extracorporeal Lithotripter

A Danish second-generation extracorporeal shock wave lithotripter (Nitech A/S) will be presented.