Interstitial cystitis and nephrogenic metaplasia. Studies on mast cells and outcome of surgical treatment

Abstract

Interstitial cystitis (IC) is characterised by urinary frequency and pain on bladder filling. Symptoms are socially restricting, sometimes disabling. The pathogenesis of IC is still unknown. Therefore, treatment is empirical and encompasses multiple conservative trials but also major and sometimes destructive reconstructive surgery. There is clearly a need to identify fundamental facts as to the pathogenesis of this crippling disease and to explore different ways of providing alleviation of symptoms.There is evidence that the mast cell system is activated in IC. It is known that the mast cell is an effector cell in allergic conditions but also that it has immunemodulating properties and is important for angiogenesis and for the development of fibrosis. The mechanisms behind mast cell recruitment, distribution and maturation in IC are essentially unknown.There are two subtypes of IC, classic and nonulcer. Although sharing similar symptomatology and a chronic course, they differ in many important respects, including age distribution, endoscopic and histological findings and response to various forms of treatment.Nephrogenic metaplasia (NM) is an unusual lesion of the urinary tract mucosa. In many cases NM goes with symptoms similar to those seen in IC.The aims of the present study were to investigate the outcome of surgical treatment and mast cell recruitment, distribution and phenotype expression in IC and NM. Data on patients were obtained from medical records and by telephone interviews. Metachromatic staining and immunohistochemical techniques were employed to visualise mast cells. Classic IC and NM expressed intraepithelial deposition of mast cells, a very rare finding in man, whereas controls, nonulcer IC and other metaplastic conditions of the urothelium did not. Classic IC and NM were also the only conditions with strong epithelial coexpression of stem cell factor (SCF) and interleukin-6 (IL-6), both known to have mast cell-activating properties. The mast cells with affinity to the epithelium of classic IC and NM expressed lack of chymase to a higher degree than did mast cells located deeper in the tissue. The majority of patients with classic IC and NM responded well to transurethral electroresection (TUR) of visible lesions. Patients with end-stage classic IC (fibrotic bladder contracture refractory to all conservative measures, including TUR) were relieved from symptoms after supratrigonal cystectomy and ileocystoplasty. This reconstructive procedure failed to help patients with nonulcer IC. Conclusions: The lack of chymase in mast cells appears to reflect the stage of maturation and/or functional activity rather than being an indicator of a fixed phenotype related to tissue site. The epithelial coexpression of SCF and IL-6 may contribute to the mast cell reaction, including the unique redistribution of mast cells into the epithelium of classic IC and NM. The SCF-receptor appears to be downregulated in both subtypes of IC. TUR of inflamed areas and bladder substitution, respectively, are effective treatments for different stages of classic IC. TUR also appears to be a suitable treatment for NM. For nonulcer IC, these two methods are unsuitable.