Improvement of interstitial cystitis symptoms and problems that developed during treatment with oral IPD-1151T

PURPOSE: We examined the efficacy of Suplatast Tosilatedouble dagger (IPD-1151T), a new immunoregulator that suppresses helper T cell mediated allergic responses, including IgE production and eosinophilic inflammation for treating patients with interstitial cystitis. MATERIALS AND METHODS: A total of 14 women (average age 43.7 years) with interstitial cystitis, which was nonulcerative in 13 and ulcerative in 1, were treated with 300 mg. IPD-1151T orally daily for 12 months. All patients received laboratory assessments, including hematology (eosinophils and CD20 positive cells) and serum chemistry (IgE, and interleukin-4 (IL-4) and 5, and immunohistochemical analyses of urine leukocytes (CD45RO positive cells as a T cell marker) before treatment. These parameters were also measured 4 and 12 months after continuous treatment. The voiding chart, and interstitial cystitis symptom and problem indexes were evaluated before and after IPD-1151T treatment. RESULTS: IPD-1151T treatment for 1 year resulted in a significantly increased bladder capacity and decreased symptoms, such as urinary urgency, frequency and lower abdominal pain, in patients with nonulcerative interstitial cystitis. These effects also correlated with a reduction in blood eosinophils, CD20 positive cells and IgE, and urine CD45RO positive memory T cells. No major side effects were observed. CONCLUSIONS: Our study suggests that immunological responses are involved in the development of interstitial cystitis symptoms. IPD-1151T could be a new oral agent for treatment of voiding symptoms and bladder pain in patients with interstitial cystitis.     

Cellular immunity in interstitial cystitis.

It has been suggested that interstitial cystitis is an autoimmune disease. The evidence for this hypothesis, based on studies of humoral immune factors, has been contradictory. We assessed the immune response in interstitial cystitis by evaluating lymphocyte populations in the peripheral blood and bladder tissue of interstitial cystitis patients. The lymphocyte phenotypes in peripheral blood were entirely normal, including the CD4 (cluster designation nomenclature) and CD8 subsets, and the CD4:CD8 ratio. Bladder lamina propria showed a predominance of CD4 over CD8 lymphocytes in interstitial and other forms of cystitis. Bladder epithelium showed a similar pattern in bacterial or mechanical cystitis but specimens from patients with interstitial cystitis had a predominance of CD8 cells. The findings of normal lymphocyte populations in the peripheral blood are not supportive of an autoimmune mechanism in the disease. The findings in bladder tissue show that the urothelium is not involved in the inflammatory reaction, as is the lamina propria, and they would suggest, therefore, that the initiating factor does not originate from the bladder lumen. The CD8 predominance in the urothelium along with a CD4 predominance in the lamina propria may form a characteristic pattern for the diagnosis of interstitial cystitis and merits further study.     

Increased number of apoptotic endothelial cells in bladder of interstitial cystitis patients

In this study, we aimed to investigate possible abnormality of bladder endothelial cells in interstitial cystitis patients by detecting morphological changes such as apoptosis in bladder endothelial cells. A bladder biopsy specimen was collected from interstitial cystitis patients immediately after hydrodistension therapy. The patients were classified into two groups on the basis of their predominant symptom, one group of patients with bladder pain and another group of patients with urinary urgency. Dissociated cells from the biopsy specimen were analyzed by flow cytometry after staining with Annexin V and an anti-CD105 antibody. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and electron microscopy were performed to confirm morphologic changes indicative of apoptosis. The percentage of Annexin V binding, an early apoptosis marker, was significantly higher in bladder endothelial cells from interstitial cystitis patients with pain [median 24.7% (range 15.1-77.2), n = 20, P < 0.01) than that from interstitial cystitis patients with urinary urgency [9.3% (range 0.7-19.11) n = 17) or control patients [1.5% (range 0.8-9.1), n = 7]. TUNEL staining showed apoptotic cells in microvascular endothelial cells but not in the endothelial cells of a venule. By electron microscopy, endothelial cells showed morphological changes indicative of apoptosis such as nuclear fragmentation. Our results indicate that increased apoptosis of bladder microvascular endothelial cells may play an important role in the pathogenesis of interstitial cystitis accompanied by bladder pain.     

Treatment of ulcer and nonulcer interstitial cystitis with sodium pentosanpolysulfate: a multicenter trial

The effect of sodium pentosanpolysulfate (Elmiron) in the treatment of interstitial cystitis was observed in an open controlled multicenter trial. We studied 87 patients with symptoms for more than 2 years at 17 centers in Finland and Sweden. Patient selection was based on the typical chronic symptomatology but the material subsequently was stratified according to objective cystoscopic findings. The medication (400 mg. daily in 2 oral doses) was discontinued after 6 months. The response was evaluated every 4 weeks during treatment and every 3 months thereafter. Most patients responded favorably, many with diminution of pain within only 4 weeks from the start of treatment. The frequency of micturition decreased significantly and the mean volume per void per 24 hours increased in the patients without bladder ulceration but such changes were not found in the patients with ulcer. The bladder capacity was smaller in the ulcer group. In these patients the pre-treatment intensity of pain was somewhat greater than in those without bladder ulcer but the pain was alleviated in both groups and this effect was stable at the 3-month followup. The differences in responses in the 2 groups indicate a probable fundamental difference between ulcerative and nonulcerative interstitial cystitis. Side effects of the drug were few, slight and transient. Therefore, the study indicates that a significant number of patients with interstitial cystitis can be expected to benefit from treatment with sodium pentosanpolysulfate.     

Bladder epithelial cells from patients with interstitial cystitis produce an inhibitor of heparin-binding epidermal growth factor-like growth factor production

PURPOSE: The etiology of interstitial cystitis is unknown. We previously identified an interstitial cystitis urine factor, antiproliferative factor, that inhibits proliferation of bladder epithelial cells in vitro and complex changes in epithelial growth factor levels, including profound decreases in heparin-binding epidermal growth factor-like growth factor (HB-EGF). Bladder and renal pelvic catheterization of patients with interstitial cystitis indicated that the antiproliferative factor is made and/or activated in the distal ureter or bladder. Therefore, we determined whether bladder epithelial cells from interstitial cystitis cases produced the antiproliferative factor and whether purified antiproliferative factor could alter production of growth factors known to be abnormal in interstitial cystitis. MATERIALS AND METHODS: Antiproliferative factor activity was determined by 3H-thymidine incorporation into primary bladder epithelial cells. The antiproliferative factor was purified by size fractionation followed by sequential chromatography involving ion exchange, hydrophobic interaction and high performance liquid chromatography. HB-EGF, epidermal growth factor, insulin-like growth factor and insulin-like growth factor binding protein 3 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Bladder epithelial cells from patients with interstitial cystitis produced a single antiproliferative factor with the same purification profile as that purified from interstitial cystitis urine. Purified antiproliferative factor specifically inhibited HB-EGF production by bladder epithelial cells in vitro, and the effect of interstitial cystitis urine or purified antiproliferative factor on bladder cell proliferation was inhibited by recombinant human HB-EGF in a dose dependent manner. Similar to urine HB-EGF, serum HB-EGF was also significantly lower in interstitial cystitis cases than in controls. CONCLUSIONS: Bladder epithelial abnormalities in interstitial cystitis may be caused by a negative autocrine growth factor that inhibits cell proliferation by down-regulating HB-EGF production. Furthermore, decreased levels of urine and serum HB-EGF indicate that interstitial cystitis may be a urinary tract manifestation of a systemic disorder.     

Histamine content and mast cell count of detrusor muscle in patients with interstitial cystitis and other types of chronic cystitis

The quantitative mast cell count in the detrusor muscle, the histamine content and the degree of collagen staining material in the bladder wall have been evaluated in order to elucidate their value in distinguishing between patients with interstitial cystitis and other types of chronic cystitis. The number of mast cells in the detrusor muscle was statistically significantly increased in patients with interstitial cystitis compared with the control group (P less than 0.0001). With a proposed level of greater than 20 mast cells/sq mm of muscle tissue the diagnostic specificity was 88% and the diagnostic sensitivity 95%. The histamine content in the bladder wall was significantly increased in patients with interstitial cystitis (P less than 0.05) but not useful as a diagnostic test. The amount of collagen staining material was significantly increased in the intra- and inter-fascicular muscle tissue of the bladder in patients with interstitial cystitis (P less than 0.0005, P less than 0.001) and might be used as a support for the histological diagnosis, even in patients with uncontracted bladders.     

Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis.

An analysis was made of the numbers and characteristics of mast cells in lateral bladder wall biopsies from 22 patients with interstitial cystitis, 6 with bacterial cystitis and 8 normal controls, using toluidine blue stains and computerised video image analysis techniques. A significantly greater number of mast cells were found within the detrusor muscle in interstitial cystitis than in bacterial cystitis or normal controls. Within the urothelium and submucosa, mast cell numbers were significantly greater than in normal controls in both interstitial and bacterial cystitis. In interstitial cystitis mast cells were significantly larger within the detrusor than in the urothelium/submucosa and they appeared to degranulate predominantly within the superficial layers. Differential staining techniques, using long and short toluidine blue stains, failed to reveal statistically significant evidence of mast cell heterogeneity within the bladder wall in interstitial cystitis.     

A型肉毒毒素膀胱三角区黏膜下注射治疗氯胺酮相关性膀胱炎的临床观察

目的探讨A型肉毒毒素(BTX-A)联合碱化利多卡因膀胱灌注+水压扩张治疗氯胺酮相关性膀胱炎的疗效。方法将33例氯胺酮相关性膀胱炎患者按治疗方式分为2组:A组15例,采用碱化利多卡因膀胱灌注+水压扩张;B组18例,在同A组治疗的基础上,加用膀胱三角区黏膜下注射BTX-A治疗。评估患者治疗前及治疗后1周、1个月、3个月的临床症状改善情况(每日排尿次数、最大排尿量、OLeary-Sant间质性膀胱炎症状评分ICSI及ICPI评分作为疗效评判标准),并记录不良反应的发生情况。结果 B组在治疗后1周、1个月、3个月症状较A组明显改善;各时间点每日排尿次数、最大排尿量、ICSI评分及CIPI评分与A组相比均有显著差异(P0.05)。两组均未出现严重不良反应。结论 BTX-A联合碱化利多卡因水压扩张治疗氯胺酮相关性膀胱炎,是一种安全有效的治疗方法,且无严重并发症。     

Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis)

Traditional concepts of impermeability of the bladder have centered around unique cellular tight junctions and ion pumps. However, recent data from our laboratory have shown that the bladder epithelium in animals and humans relies primarily on its surface glycosaminoglycans to maintain its impermeability. This study demonstrates the first disease associated with an epithelial dysfunction of the bladder, that is a leaky epithelium. The study consisted of 31 normal subjects and 56 individuals with interstitial cystitis. Interstitial cystitis patients were shown to have a leaky epithelium by placing a solution of concentrated urea into the bladder and measuring the absorption. The normal subjects absorbed 4.3% in 45 minutes, while the interstitial cystitis patients absorbed 25% (difference is highly significant, p less than 0.005). Interstitial cystitis patients with Hunner's ulcers (10) had a 34.5% absorption rate, while those without ulcers absorbed 22.8% (46). This difference also was highly significant (p = 0.002) and supports the concept that patients with ulcers have clinically worse disease.     

Do women with idiopathic sensory urgency have early interstitial cystitis?

Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics. Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity, with both early and late forms of the disease being described. Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist. We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis). No control patient showed such an increase. Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency.     

Complete Transurethral Resection of Ulcers in Classic Interstitial Cystitis

Interstitial cystitis (IC) is a chronic disease of obscure etiology. It commonly affects females, who present with symptoms of pain on bladder filling and urinary frequency. There are two types of IC: classic and non-ulcer disease, which differ in many respects, including response to different therapies. In this retrospective study we evaluated the hitherto largest series of patients with classic IC treated by transurethral resection (TUR) of visible ulcers. Altogether 259 TURs of Hunner ulcers were performed on 103 patients: 92 experienced amelioration, and in 40% symptom relief lasted more than 3 years. In the remaining patients, although symptom recurrence was common, the majority responded well to subsequent TUR. In conclusion, TUR has a good outcome in patients with classic interstitial cystitis, and we suggest it as first-line treatment in this patient group.     

Sequential hydrodistension and intravesical instillation of hyaluronic acid under general anaesthesia for treatment of refractory interstitial cystitis: a pilot study

Pilot study looking at the combination of general anaesthetic hydrodistension and intravesical hyaluronic acid for treatment of refractory interstitial cystitis. Twenty-three treatment refractory patients were recruited with an average age 53.4 years. All underwent general anaesthetic cystoscopy, hydrodistension and instillation of hyaluronic acid (40 mg/50 ml). The bladder was then subsequently drained with the patient awake. Two initial treatments were carried out a month apart and duration between treatments increased depending upon symptom response. In the responders, the average number of treatments was 6.6 (median 4.5), duration between treatments was 3.1 months (median 2.6) and follow-up 15.8 months (median 16). Seventeen patients (74%) responded with immediate improvement in symptoms. In all responders, healing of ulceration and resolution of inflammation occurred. Average anaesthetic bladder capacity increased in the responder group from an average of 492 ml (median 500 ml) to an average of 776 ml (median 700 ml). Our pilot data suggests sequential hydrodistension and hyaluronic acid treatment under general anaesthesia may be considered for resistant cases of interstitial cystitis, especially those that cannot tolerate the instillation procedure under local anaesthesia. Further prospective trials are required.     

间质性膀胱炎组织中Uroplakin基因家族表达的临床意义

目的 探讨间质性膀胱炎(IC)组织中Uroplakin(UP)基因家族表达的临床意义.方法 采用RT-PCR方法 检测29例IC患者膀胱黏膜组织标本中UP Ia、Ib、II、III以及III-δ4 mRNA(UP III选择性黏接变异体)的表达,免疫组化染色法检测UP III蛋白表达.16例正常膀胱黏膜组织标本作为对照组.结果 IC患者膀胱黏膜组织中UP III-δ4 mRNA表达中位值为4.80,对照组为0.22,组间差异有统计学意义(P<0.001);无Hunner溃疡患者膀胱黏膜组织中UP Ia、Ib、II、III以及III-δ4 mRNA基因表达值分别为4.99、3.31、2.75、15.38、11.48,显著高于有溃疡组的0.04、0.29、0.09、0.11、0.34,组间差异有统计学意义(P<0.01).有溃疡组UP Ia、Ib、II、III mRNA表达值均显著低于正常对照组的3.22、4.22、3.06、0.95,组间差异有统计学意义(P<0.01);无溃疡组中UP III与UP III-δ4 mRNA表达水平显著高于对照组,表达中位值分别为对照组的5.6倍(15.38与2.76)和26.5倍(11.48与0.43).UP基因表达与其他临床指标无显著相关.结论 IC膀胱黏膜组织中UP基因家族表达发生异常改变,UP III-δ4 mRNA有可能成为非溃疡型IC的特异性标志物.

Abstract：

Objective To detect gene expressions of Uroplakin (UP) family in interstitial cystitis (IC). Methods Gene expression of UP Ia, Ib, II, III, and III-δ4 was quantitatively measured in bladder biopsy samples from patients with IC (n=29) and control subjects (n=16) using real-time RT-PCR. Results UP III-delat4, a splicing variant of UP III, was significantly up-regulated to 4.80 in IC samples (P<0.001). When IC patients were divided into two groups, one with and one without ulcerative changes, the UP Ia, UP Ib, UP II, UP III and III-δ4 genes were significantly up-regulated to 4.99, 3.31, 2.75, 15.38, 11.48 in nonulcerative IC patients, but decreased to 0.04, 0.29, 0.09, 0.11, 0.34 in ulcerative IC patients (P<0.01). The up-regulation of UP III-δ4 was more prominent than that of UP III: 26.5-fold versus 5.6-fold compared to the median values of normal subjects. Conclusion Although the clinical implications of the over-expression of UP III and III-δ4 in non-ulcerative IC bladders remain to be clarified, from the diagnostic viewpoint, UP III-δ4 is a potential marker for identifying nonulcerative IC.     

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.     

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.     

BLADDER MICROVASCULATURE IN WOMEN WITH INTERSTITIAL CYSTITIS

PURPOSE: A cardinal cystoscopic finding in women with interstitial cystitis is mucosal small vessel hemorrhage or glomerulations after hydrodistention. We quantified and compared microvascular density and endothelial proliferation in the bladder biopsies of women with interstitial cystitis and a control group of women who were undergoing incontinence or prolapse surgery. MATERIALS AND METHODS: We performed computer assisted image analysis and immunohistochemical studies to compare differences in the blood vessel count, and proportional area in the bladder suburothelium and deeper submucosa of bladder biopsies of 52 women, including 26 with interstitial cystitis. Routine light microscopy features were examined and correlated with microvascular density. RESULTS: In the bladder biopsies of women with interstitial cystitis there was a lower blood vessel count (p = 0.01), and a lower proportion of the total image consisted of blood vessel wall (p = 0.03) in the suburothelium than in control biopsies. We noted no difference in the blood vessel count of the deeper submucosa or in the degree of endothelial cell proliferation. Suburothelial blood vessel differences correlated with the degree of histological change, such as edema, inflammatory infiltrate and vascular congestion. CONCLUSIONS: We found decreased microvascular density in the suburothelium but not in the deeper submucosa in bladder biopsies of women with interstitial cystitis.     

A型肉毒毒素膀胱内不同部位注射治疗女性膀胱疼痛综合征/间质性膀胱炎的临床研究

目的 比较A型肉毒毒素膀胱内逼尿肌注射以及逼尿肌联合三角区注射两种不同注射方法治疗女性膀胱疼痛综合征/间质性膀胱炎的疗效以及安全性.方法 60例入选病例,随机分为两组:逼尿肌注射组(A组)、逼尿肌联合三角区注射组(B组),评估两组患者治疗前及治疗后8周的平均每日排尿次数、最大排尿量、残余尿量、PUF评分、QOL评分.结果 A组及B组治疗后平均每日排尿次数减少,最大排尿量增加,PUF及QOL评分降低,残余尿量无明显增加,B组治疗后与A组治疗后相比,平均每日排尿次数、最大排尿量及PUF评分改善更明显,残余尿量与QOL评分无明显区别.结论 A型肉毒毒素膀胱内注射治疗女性膀胱疼痛综合征/间质性膀胱炎疗效好,生活质量提高,采用逼尿肌联合三角区部位的注射,症状缓解更为明显,副作用无明显增加,值得进一步研究及推广.     

Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis

PURPOSE: The etiology of interstitial cystitis is unknown. Urine from patients with interstitial cystitis has been shown to inhibit urothelial proliferation through a putative antiproliferative factor and to contain decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) compared to controls. Stretch of detrusor smooth muscle cells is known to stimulate HB-EGF production. Because bladder hydrodistention sometimes alleviates the symptoms of interstitial cystitis, we determined whether the stretch stimulus of hydrodistention alters antiproliferative factor activity and/or HB-EGF in interstitial cystitis urine specimens. MATERIALS AND METHODS: Urine was collected immediately before, and 2 to 4 hours and 2 weeks after hydrodistention from 15 patients with symptoms and cystoscopic findings compatible with interstitial cystitis and 13 controls. Hydrodistention was performed with the subject under general or regional anesthesia and bladders were distended to 80 cm. water 3 times. Urinary HB-EGF was measured by enzyme-linked immunosorbent assay and urinary antiproliferative factor activity was determined by measuring 3H-thymidine uptake by normal human bladder urothelial cells. RESULTS: Hydrodistention significantly increased urinary HB-EGF in patients with interstitial cystitis toward normal control values (before distention p = 0.003, 2 weeks after distention p = 0.67). Urine antiproliferative factor activity decreased significantly after hydrodistention in patients with interstitial cystitis. However, antiproliferative factor activity in interstitial cystitis and control specimens was still statistically different 2 weeks after distention (before distention p = 0.0000004, 2 weeks after distention p = 0.04). CONCLUSIONS: Bladder stretch increased HB-EGF and conversely reduced antiproliferative factor activity in urine from patients with interstitial cystitis but not controls up to 2 weeks after distention. These results provide additional evidence for the possible role of antiproliferative factor and decreased HB-EGF in the pathophysiology of interstitial cystitis. To our knowledge this is also the first human study to show that in vivo bladder stretch can alter urinary factors that regulate cell growth.     

USE OF THE NEODYMIUM: YAG LASER FOR INTERSTITIAL CYSTITIS: A PROSPECTIVE STUDY

PURPOSE: Interstitial cystitis is a disorder of the bladder characterized by urgency and frequency of urination, and pelvic pain. The classic type of interstitial cystitis is characterized by Hunner's ulcers, which are focal regions of severe bladder inflammation. Patients with Hunner's ulcers tend to have more severe symptoms and are often refractory to medical management. We present a prospective series of patients who underwent ablative therapy of Hunner's ulcers using a neodymium (Nd):YAG laser. MATERIALS AND METHODS: A total of 24 patients with interstitial cystitis underwent ablative therapy for Hunner's ulcers. Medical therapy had failed in all cases. Using regional or general anesthesia the Nd:YAG laser under cystoscopic control was used to ablate the ulcers. The power setting was 15 W. with a firing duration of between 1 and 3 seconds. The procedure was performed on an outpatient basis. Symptoms were noted preoperatively and postoperatively. RESULTS: All patients had symptom improvement within 2 to 3 days. The mean pain scores decreased from 9.1 to 1.2 (p <0.003), the mean urgency score decreased from 8.2 to 1.9 (p <0.003), the mean voiding interval increased from every 30 minutes to every 102 (p <0.0001) and nocturia decreased from a mean of 7.9 voids per night to 2.9 (p <0.0001). There were no complications. Mean followup was 23 months. However, relapse in 11 patients required 1 to 4 additional treatments. The re-treatment response was similar to the initial treatment. CONCLUSIONS: Nd:YAG laser ablation of Hunner's ulcers is an excellent, minimally invasive method of treating interstitial cystitis. While it is not a cure, it offers patients an opportunity to have decreased symptoms for an extended period and it may be repeated as necessary.     

Scanning electron microscopic findings in interstitial cystitis

Scanning electron microscopy (SEM) was performed on transurethral resection biopsies from 13 patients with classic interstitial cystitis. Biopsies from 9 patients with stress incontinence served as controls. The SEM appearance of the bladder surface in interstitial cystitis varied considerably, exhibiting small round and large polygonal cells. The proportion of cells displaying round uniform and pleomorphic microvilli was high and sometimes dominated the area examined. SEM characteristics earlier assigned to bladder tumours were detected in patients with interstitial cystitis and, at a lower frequency, also in control patients. The mucin layer covering the urothelial cells seemed reduced in interstitial cystitis compared with control specimens. Surface characteristics specific for interstitial cystitis were, however, not detected by SEM.