Preliminary results of suburothelial injection of botulinum a toxin in the treatment of chronic interstitial cystitis

PURPOSE: Treatment of interstitial cystitis is usually not successful in eradicating bladder pain and increased bladder capacity. This study was designed to evaluate the clinical effectiveness of suburothelial injection of botulinum A toxin in patients with chronic interstitial cystitis. METHODS: Eight women and 2 men with chronic interstitial cystitis who had failed conventional treatments were enrolled in this study. In 5 patients, 100 units of botulinum A toxin was injected suburothelially into 20 sites, and an additional 100 units was injected into the trigone in the other 5 patients. Therapeutic outcome including functional bladder capacity, number of daily urinations, bladder pain, and urodynamic changes were compared between baseline and 3 months after treatment. RESULTS: In 2 patients bladder pain and urinary frequency were improved 3 months after treatment. Mild difficulty in urination was reported by 7 patients. Functional bladder capacity recorded in a voiding diary was significantly increased (155+/-26.3 vs. 77+/-27.1 ml, p<0.001), and the frequency of daily urinations (18+/-7.7 vs. 24.2+/-10.3, p=0.025) and the pain score (2.4+/-1.6 vs. 3.2+/-1.1, p=0.003) were mildly but significantly reduced after treatment. Only the cystometric capacity improved significantly (287+/-115 vs. 210+/-63.8 ml, p=0.05) in urodynamic results. Trigonal injection had no therapeutic effect on symptom or urodynamic improvement. No adverse effect was reported. CONCLUSIONS: The clinical result of suburothelial botulinum A toxin injection was disappointing. None of the patients was symptom free and only a limited improvement in bladder capacity and pain score was achieved in 2 patients.     

Possible mechanisms inducing glomerulations in interstitial cystitis: relationship between endoscopic findings and expression of angiogenic growth factors

PURPOSE: Glomerulation has been one of the requisite criteria for the diagnosis of interstitial cystitis (IC) but the mechanisms for glomerulation remain unclear. Therefore, we investigated the relationship between the cystoscopic findings of vascular events and the expression of angiogenic growth factors in IC bladders to identify the possible mechanisms inducing glomerulations in IC. MATERIALS AND METHODS: In 45 patients suspected of having IC continuous, fixed point cystoscopic observation was performed during hydrodistention using spinal anesthesia. Bladder biopsies were performed in these cases and in an additional 5 asymptomatic cases. Thereafter, the expression of platelet derived endothelial cell growth factor/thymidine phosphorylase (PDECGF/TP) was measured by enzyme-linked immunosorbent assay. Immunohistochemical staining for PDECGF/TP and vascular endothelial growth factor was also performed. RESULTS: Of 45 symptomatic patients 38 had glomerulations during cystoscopic examination. In these patients during hydrodistention the blood flow in bladder wall vessels was interrupted by whitish fibrous bundles. Thereafter petechial bleeding began from capillaries distal to obstructed vessels during bladder emptying. PDECGF/TP expression in patients with glomerulation was significantly higher than in symptomatic patients without glomerulation or asymptomatic patients (p < 0.001). In patients with glomerulations a high positive rate for PDECGF/TP (97.4%) and vascular endothelial growth factor (68.4%) staining was observed, while no positive staining was found in asymptomatic patients. CONCLUSIONS: Glomerulations during hydrodistention are highly associated with the over expression of angiogenic growth factors in the bladder. Thus, it seems likely that neovascularization promoted by angiogenic growth factors has an important role in the pathogenesis of IC, inducing glomerulations during hydrodistension.     

Nitric oxide: a useful gas in the detection of lower urinary tract inflammation.

PURPOSE: Luminal nitric oxide has been shown to be elevated in the bladder of patients with cystitis of various etiologies. We determine whether luminal nitric oxide can be used as a marker to differentiate inflammation, that is interstitial cystitis, from urgency, frequency, nocturia and pain due to noninflammatory disorders, such as outflow obstruction and neurogenic dysfunction. MATERIALS AND METHODS: We measured luminal nitric oxide in the bladder of patients with urgency due to detrusor instability (6), outflow obstruction (7), sensory urge (19) and interstitial cystitis (8), and controls without urgency symptoms (11). Nitric oxide-free air was incubated in the bladder for 5 minutes and analyzed in a chemiluminescence nitric oxide analyzer. RESULTS: There was a nearly 20-fold increase in mean bladder nitric oxide concentration in patients with interstitial cystitis (234+/-67 parts per billion) compared to those with detrusor instability (11+/-1), outflow obstruction (9+/-1) and sensory urgency (10+/-1), and controls (13+/-2). CONCLUSIONS: Measurement of nitric oxide in air from the bladder is a simple, safe and fast method to differentiate urgency due to inflammation from neurogenic disorders or outflow obstruction. The simplicity of this method makes it potentially useful as a screening method for office use.     

Interstitial cystitis,bladder pain syndrome,hypersensitive bladder,and interstitial cystitis/bladder pain syndrome – clarification of definitions and relationships

Interstitial cystitis and interstitial cystitis‐related conditions such as bladder pain syndrome and hypersensitive bladder have a similar symptomatic profile but probably different etiologies. A meaningful classification of these diseases/conditions is mandatory for clinical and investigational progress. The condition with Hunner lesions (Hunner type interstitial cystitis) is distinct from other categories in terms of histopathology, gene expression, and clinical management. Classification should clearly differentiate the presence or absence of Hunner lesions. The term covering patients as a whole should contain interstitial cystitis, since interstitial cystitis is historically a well‐known name and used for insurance reimbursement. The proposed taxonomy features an umbrella term (interstitial cystitis/bladder pain syndrome) and two subgroups, Hunner type interstitial cystitis (with Hunner lesions) and bladder pain syndrome (without Hunner lesions). Interstitial cystitis/bladder pain syndrome is convenient for initial management, and subgroups can categorize the patients for specific management. The characteristic symptom profile is to be collectively termed as hypersensitive bladder symptoms.     

Clinical guidelines for interstitial cystitis/bladder pain syndrome

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.     

In vivo hepatocyte growth factor gene transfer to bladder smooth muscle after bladder outlet obstruction in the rat: a morphometric analysis

PURPOSE: We determined whether hepatocyte growth factor gene transfer after partial bladder outlet obstruction would prove effective for decreasing transforming growth factor-beta expression and consequently decreasing collagen deposition in partially obstructed rat bladders. MATERIALS AND METHODS: Ten-week-old male Sprague-Dawley rats were divided into 3 groups of 10 each, including group 1--sham operation, group 2--bladder outlet obstruction for 4 weeks and group 3--hepatocyte growth factor gene transfer after bladder outlet obstruction. Two weeks after the onset of bladder outlet obstruction in group 3 hepatocyte growth factor-liposome complex (50 microg human hepatocyte growth factor cDNA) was injected into the smooth muscle of the rats. RESULTS: We noted no difference between groups 2 and 3 with regard to the ratio of bladder weight to body weight. The ratio in groups 2 and 3 was significantly higher than in group 1 (p = 0.043). The mean percent of collagen area +/- SE was 36.32% +/- 1.83%, 27.90% +/- 2.66% and 8.97% +/- 3.35% in groups 1 to 3, respectively (p <0.05). Relative hepatocyte growth factor and c-met mRNA and protein expression were higher in group 3 than in groups 1 and 2. However, the expression of transforming growth factor-beta1 mRNA and protein was higher in group 2 than in groups 1 and 3. CONCLUSIONS: These findings may imply a possible novel therapeutic strategy against bladder dysfunction arising in patients with bladder outlet obstruction.     

Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?

PURPOSE: We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction. MATERIALS AND METHODS: Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-beta and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides. RESULTS: Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-beta1 than unobstructed kidneys (79.1 +/- 8.3 versus 33.6 +/- 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 +/- 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 +/- 5.4 versus 2.2 +/- 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 +/- 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 +/- 3.4 versus 3.9 +/- 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 +/- 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac. CONCLUSIONS: The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-beta, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.     

血小板衍化内皮细胞生长因子/胸腺嘧啶磷酸酶和血管内皮生长因子在间质性膀胱炎诊断中的应用

目的 检测血小板衍化内皮细胞生长因子/胸腺嘧啶磷酸酶(PDECGF/TP)和血管内皮生长因子(VEGF)的表达,探讨血管生长因子在间质性膀胱炎(IC)患者膀胱中的表达活性与膀胱镜下的表现及临床症状的关系.方法 选择符合NIH/NIDDK诊断标准的IC患者12例为实验组和12例Ⅲ型前列腺炎患者为对照组.实验组行麻醉下水扩张,膀胱组织活检,常规苏木素-伊红(HE)染色观察肥大细胞数量.应用免疫组织化学检测PDECGF/TP和VEGF表达,进行免疫组织化学阳性细胞计数及免疫组织化学评分(IHS).结果 实验组12名患者在麻醉下水扩张时发现膀胱黏膜点片状出血.常规HE染色病理切片观察可见IC组膀胱组织标本中肥大细胞数目明显高于对照组(P＜0.05),且IC患者的肥大细胞多存在于膀胱组织的黏膜下层,而对照组膀胱组织仅偶见肥大细胞.实验组患者膀胱黏膜PDECGF/TP和VEGF阳性细胞百分比计数、阳性细胞染色强度及HIS评分明显高于对照组(P＜0.05).结论 IC患者血管生长因子PDECGF/TP和VEGF呈高水平表达,通过检测PDECGF/TP和VEGF能够筛选或确诊间质性膀胱炎.

Abstract：

Objective To find out the relationship among the expression of vascular growth factors in patients with interstitial cystitis (IC) and their performance under the cystoscopy as well as the clinical symptoms by detecting the expression of platelet-derived endothelial growth factor/thymine phosphatase (PDECGF/TP) and vascular endothelial growth factor (VEGF). Methods Twelve cases of IC served as the experimental group and 12 cases of type Ⅲ as the control group. The patients in experimental group had bladder mucosa biopsy. The number of mast cells was observed by HE staining. The expression of PDECGF/TP and VEGF and immunohistological score (IHS) were detected by using immunohistochemistry. Results Bladder mucosa hemorrhage points and sheets were observed under water expansion. The number of mast cells existing in the submucosa of the bladder tissue was significantly greater than in control group (P ＜ 0. 05 ). The percentage of PDECGF/TP and VEGF positive cells and IHS in experimental group were significantly higher than in control group (P ＜ 0. 05). Conclusion The expression of PDECGF/TP and VEGF was up-regulated in patients with IC. IC can be screened out or diagnosed by detecting PDECGF/TP and VEGF.     

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.     

Patients With Chronic Pelvic Pain: Endometriosis or Interstitial Cystitis/Painful Bladder Syndrome?

BACKGROUND: Endometriosis and interstitial cystitis/painful bladder syndrome share similar symptoms. Interstitial cystitis was once considered rare, but it is now recognized as more common than previously thought. This review examines evidence that patients presenting with symptoms typically attributed to endometriosis or with unresolved pelvic pain after treatment for endometriosis may, in fact, have interstitial cystitis, and suggests approaches for appropriate diagnosis. METHODS: A MedLine search using "chronic pelvic pain," "endometriosis," "interstitial cystitis," and "bladder origin pain" as key words was performed for the most recent English-language articles. Additional references were obtained through cross-referencing the bibliography cited in each publication. DISCUSSION: The symptoms of endometriosis and interstitial cystitis frequently overlap, and these 2 conditions may even coexist in the same patient. In cases of unresolved endometriosis and persistent pelvic pain, patients may have interstitial cystitis. A variety of tools are available to aid in identifying interstitial cystitis. CONCLUSION: Gynecologists should be alert to the possible presence of interstitial cystitis in patients who present with chronic pelvic pain typical of endometriosis.     

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.     

Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis

PURPOSE: Extracellular adenosine triphosphate (ATP) has been shown to mediate inflammation and nociception and, therefore, it may have a role in symptoms associated with interstitial cystitis. We theorized that the bladder uroepithelium releases ATP in response to stretch and, furthermore, this process is augmented in interstitial cystitis. MATERIALS AND METHODS: We quantitated ATP using the luciferin-luciferase assay. Urinary ATP levels were compared in 35 patients with interstitial cystitis and in 33 normal controls after pH correction. Cultured interstitial cystitis and normal urothelial cells from the bladder biopsies of 5 patients each were stretched with the Flexcell 2000 machine (Flexcell International Corp., McKeesport, Pennsylvania) and supernatant ATP concentrations were measured. RESULTS: Mean urinary ATP plus or minus standard error of mean was significantly higher in patients with interstitial cystitis than in controls (L value 985 +/- 161 versus 377 +/- 27, p = 0.0007). Supernatant ATP released by stretched interstitial cystitis cells was stretch intensity dependent when comparing 0%, 10% and 20% elongation, and was also significantly higher in stretched interstitial cystitis than in stretched normal cells. CONCLUSIONS: Adenosine triphosphate was significantly elevated in the urine of individuals with interstitial cystitis and the stretch activated release of ATP was augmented in interstitial cystitis urothelium. Increased extracellular ATP may have a role in mechanosensory transduction and to our knowledge it represents a novel hypothesis.     

Urinary neutrophil chemotactic factors in interstitial cystitis patients and a rabbit model of bladder inflammation.

The present study investigates a possible source of inflammatory mediators involved in the pathogenesis of bladder inflammation characteristics of interstitial cystitis disease. Our tested hypothesis is that in response to injury, tissues of the urinary bladder participate in the initiation of bladder inflammation by releasing inflammatory mediators such as neutrophil chemotactic factors. Bladders of anesthetized rabbits (n = 7) were instilled with an acidic solution (pH 4.5) for 15 minutes, then washed with saline and instilled with sterile phosphate buffered saline (PBS) (pH 7.2) for an additional 45 minutes prior to sacrificing the rabbits. Control rabbits (n = 7) were instilled with sterile PBS (pH 7.2) for 15 minutes, then 45 minutes. The levels of neutrophil chemotactic factors were measured using modified Boyden chambers and rabbit peritoneal neutrophils as indicator cells. Results indicated the release of high levels of neutrophil chemotactic factors (via a checkerboard analysis) from acid-treated bladders after 15 minutes (70 +/- 4% of standard) and 45 minutes (80 +/- 7%). Electron microscopy analysis of these acid-treated bladders revealed the infiltration of a large number of neutrophils, which correlates with the recovery of neutrophil chemotactic factors. Control rabbits, on the other hand, showed low levels of chemotactic activity (less than 10 percent) and exhibited normal bladder morphology with absence of neutrophils. The glycosaminoglycan (GAG) layer was intact in both acid-treated and control bladders. High levels of neutrophil chemotactic factors were also detected in urine samples from eleven patients with interstitial cystitis (113 +/- 25%) (not due to interleukin-1 or leukotriene B4) which were not detected in urine samples from healthy volunteers (n = 9) or from thirteen control patients with bladder diseases other than interstitial cystitis. These preliminary studies indicate the capability of injured bladder tissues to release neutrophil chemotactic factors which contribute to the initiation of bladder inflammation. The presence of neutrophil chemotactic factors in urine samples of interstitial cystitis patients suggests a possible role of these mediators in the pathogenesis of the disease.     

Interstitial cystitis and endometriosis in patients with chronic pelvic pain: The "Evil Twins" syndrome.

OBJECTIVE: To determine the prevalence of interstitial cystitis and endometriosis in patients with chronic pelvic pain. METHODS: A prospective analysis was conducted in 178 women with CPP who presented with bladder base/anterior vaginal wall and/or uterine tenderness, with or without irritative voiding symptoms. The Potassium Sensitivity Test was used to assess bladder epithelial dysfunction. Patients were evaluated with concurrent laparoscopy and cystoscopy with hydrodistention. RESULTS: Laparoscopic findings among the 178 patients with chronic pelvic pain supported a diagnosis of endometriosis in 134 (75%) patients, and cystoscopy confirmed a diagnosis of interstitial cystitis in 159 (89%) patients. Both interstitial cystitis and endometriosis were diagnosed in 115 patients (65%). The Potassium Sensitivity Test was positive in 146 (82%) patients, with 140 (96%) of these patients diagnosed with interstitial cystitis and 105 (72%) with endometriosis. CONCLUSIONS: Results of this prospective study show that interstitial cystitis and endometriosis may frequently coexist in patients with chronic pelvic pain. A positive Potassium Sensitivity Test accurately predicted the presence of interstitial cystitis in 96% of these patients with chronic pelvic pain, as confirmed by cystoscopic hydrodistention. It is necessary to consider the diagnosis of endometriosis and interstitial cystitis concurrently in the evaluation of patients with chronic pelvic pain to avoid unnecessary delay in identifying either condition.     

Effect of comestibles on symptoms of interstitial cystitis

PURPOSE: Anecdotal evidence suggests that patients with painful bladder syndrome/interstitial cystitis report symptom exacerbation after consuming particular foods, beverages and/or supplements. We determined the prevalence of the effect of comestibles on painful bladder syndrome/interstitial cystitis symptoms and identified particular comestible items more likely to affect such symptoms. MATERIALS AND METHODS: A validated questionnaire designed to detect whether food, beverages and/or supplements have an effect on bladder symptoms was administered to 104 patients meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis. In addition to answering general questions about the effect of comestibles on painful bladder syndrome/interstitial cystitis symptoms, subjects were asked to indicate whether each of 175 individual items worsened, improved or had no effect on symptoms. Each response was numerically scored on a scale of -2 to 2 and mean values were generated for each comestible item. RESULTS: Of the surveyed patients with painful bladder syndrome/interstitial cystitis 90.2% indicated that the consumption of certain foods or beverages caused symptom exacerbation. There was no correlation between allergies and the effect of comestibles on symptoms. Patients who reported that specific foods worsened symptoms tended to have higher O'Leary-Sant interstitial cystitis symptom index and problem index, and/or pelvic pain and urgency/frequency patient symptom scale scores. A total of 35 comestible items had a mean score of lower than -1.0, including caffeinated, carbonated and alcoholic beverages, certain fruits and juices, artificial sweeteners and spicy foods. CONCLUSIONS: There is a large cohort of patients with painful bladder syndrome/interstitial cystitis in whom symptoms are exacerbated by the ingestion of specific comestibles. The most frequently reported and most bothersome comestibles were coffee, tea, soda, alcoholic beverages, citrus fruits and juices, artificial sweeteners and hot pepper.     

Interstitial cystitis: early diagnosis, pathology, and treatment.

In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form.     

Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis

Two patients with histologically confirmed interstitial cystitis underwent bladder augmentation procedures (clam cystoplasty and Mainz pouch cystoplasty) because of therapy resistant low abdominal pain and decreased functional bladder capacity. However, symptoms of low abdominal pain and urinary retention (1 patient) persisted, and cystectomy was performed in both patients after 14 and 20 months, respectively. Histological examination of the specimens showed changes in the intestinal areas of the augmented bladder, resembling interstitial cystitis. The etiology of this phenomenon and the possible role of intestinal interstitial cystitis in augmentation failures are discussed.     

Phenotyping of interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome is a chronic, potentially debilitating condition characterized by pain perceived to be related to the bladder in conjunction with lower urinary tract symptoms, and includes a wide variety of clinical phenotypes with diverse etiologies. Currently the only clinically relevant proven phenotype of interstitial cystitis/bladder pain syndrome is the Hunner lesion. Whether the presence of Hunner lesions is a hallmark of a distinct disease cohort or a potentially transient feature of non‐Hunner lesion phenotype has been debated but remains controversial. There are few documented examples of a patient converting between the two forms. Growing clinical and basic evidence supports eliminating the Hunner lesion phenotype from the bladder pain syndrome umbrella and considering it a distinct disease. The Hunner lesion phenotype is characterized by distinct bladder histology, including subepithelial chronic inflammatory changes and epithelial denudation, and specific clinical characteristics (older onset age, severe bladder‐centric symptoms, reduced bladder capacity, and favorable response to the lesion‐targeted therapies). To define the Hunner lesion phenotype, it is necessary to develop an atlas of standardized images of cystoscopic (and, if possible, pathological) appearances of Hunner lesions. A true potential and clinically relevant phenotype of interstitial cystitis/bladder pain syndrome may be patients with non‐bladder‐centric symptoms, characterized by the affect dysregulation and somatic symptoms, and a greater bladder capacity in absence of Hunner lesions. In the present workshop, we concluded that the Hunner lesion is a valid phenotype and can reasonably be considered a disease in its own right. Assessment of bladder capacity and the extent of symptoms (bladder beyond or bladder centric) may help phenotyping of interstitial cystitis/bladder pain syndrome. Proper phenotyping is essential for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome, and for facilitating research.