Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study

doi:10.1016/S0090-4295(01)01166-9

Urology

Volume 57, Issue 6, Supplement 1, June 2001, Pages 67-81

https://doi.org/10.1016/S0090-4295(01)01166-9 Get rights and content

Abstract

The purpose of this study was to investigate associations between bladder biopsy features and urinary symptoms for patients enrolled in the Interstitial Cystitis Database (ICDB) Study. Bladder biopsies were obtained during baseline screening in the ICDB Study and were evaluated for histopathologic features. Multivariable models for nighttime voiding frequency, urinary urgency, and pain were developed, incorporating biopsy features from the most diseased area of the bladder as predictors, adjusting for significant clinical factors, and clinical center variation. Among 204 interstitial cystitis (IC) patients providing biopsy specimens, cystoscopic pathology findings were not statistically associated (P >0.1) with primary IC symptoms, although the presence of Hunner’s ulcer (n = 12) was suggestive of increased urinary frequency. Within a multivariable predictive model for nighttime voiding frequency, adjusting for age and minimum volume per void, 4 pathology features were noted: (1) mast cell count in lamina propria on tryptase stain; (2) complete loss of urothelium; (3) granulation tissue in lamina propria; and (4) vascular density in lamina propria on factor VIII (F8) stain were statistically significant (P <0.01). Similarly, in a multivariable model for urinary urgency, minimum volume, and percentage of submucosal granulation tissue remained statistically significant (P <0.01). Finally, the percentage of mucosa denuded of urothelium and the percentage of submucosal hemorrhage remained highly associated (P <0.01) with pain in a multivariable predictive model. The fact that the presence or severity of glomerulations was not selected for any of these predictive models suggests that cystoscopic findings of glomerulations are not predictive of IC symptoms. Furthermore, these results suggest an important role for certain pathologic features in the predictive modeling of IC symptoms.

Section snippets

Biopsy protocol

The biopsy protocol for the ICDB Study prescribed 2 samples to be selected from the most diseased area of the bladder, using a hierarchy of cystoscopic appearances as follows:

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If the patient had a Hunner’s ulcer, then 2 sets (not closer than within 0.5 mm of each other) were to be sampled in the area of the ulcer.
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If the patient did not have a Hunner’s ulcer, but had glomerulations, then 2 sets (not closer than within 0.5 mm of each other) were to be sampled in the area of the glomerulations.
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If

Selection factors for bladder biopsy

As noted in previous reports, 637 patients were enrolled into the ICDB Study between May 1993 and January 1997. Although obtaining bladder biopsies was not a protocol requirement at baseline screening, 226 patients did undergo a cystoscopy under anesthesia, of which 211 provided bladder biopsies, either at baseline screening or at the 1-month follow-up visit. The overall biopsy rate among ICDB Study patients was 33% (211 of 637), ranging from 9% (University of California San Diego) to 64%

Discussion

Although pathophysiologic processes have been proposed for IC, none has been conclusively confirmed. Moreover, the histopathologic definition of IC, as well as the relations between the pathologic features and patient symptoms, are poorly described. The classic description of IC as being equated with an “elusive” bladder ulcer as described by Hunner in 1914,12 and its corresponding cystoscopic appearance as patches of red mucosa exhibiting small vessels radiating to a central pale scar, was the

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^☆: This work was supported by Cooperative Agreements U01-DK-45021, U01-DK-54127, U01-DK-45859, U01-DK-54127, U01-DK-45013, U01-DK44998, U01-DK-45022, and U01-DK-45026 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

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Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study☆

Abstract

Section snippets

Biopsy protocol

Selection factors for bladder biopsy

Discussion

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