The role of GAG's in the pathology of interstitial cystitis (IC/PBS)

Interstitial cystitis is a bladder disease. It causes a recurrent sterile
inflammation of the bladder wall resulting in pelvic pain, urgency (an
uncontrollable and uncomfortable desire to urinate) and frequency (voiding >
8x/day). The pathogenesis of this disease is still unknown, but two of the
histological diagnostic features are 1) an increase of invading solutes and
proteins from the urine into the bladder wall, due to an impairment of the
bladder barrier and 2) an unusual colonisation of mast cells (inflammatory
cells) in the bladder wall. Previous histological research (Hurst 1996, Parsons
1991) on bladder of interstitial cystitis patients detected a defect of the
glycosaminoglycan (GAG) layer. The GAG-layer is part of the mucus layer of the
bladder and is considered to be the first line of defence in keeping the
bladder wall barrier intact. The defect that is seen in the GAG-layer of
interstitial cystitis, could attribute or even be responsible for the recurrent
bladder inflammation and cause the typical histological abnormalities seen in
these patients. Research at our own department provided new insight on the
contents of the bladder GAG-layer. Also, recent research on kidney revealed
that mast cells excrete the enzyme haparanase. Heparanase is known to break
down heparan sulfate, an important GAG in the human bladder. Our hypothesis is
that heparanase from mast cells are responsible for the GAG-layer defects in
IC.

Our goal is to investigate the differences in the GAG-layer of patients with
normal bladders and interstitial cystitis. We also want to evaluate the role of
mast cells and heparanase in the pathogenesis of interstitial cystitis.

observational study; using bladder biopsies for histological research
(hypothesis finding study)

2 bladder biopsies per patient will be taken for research purposes (this is
besides the regular diagnostic biopsies).

The patients will undergo bladder biopsies. This will be done via an
cystoscope, which is a device that has long tube with a small diameter, that
can be inserted minimally invasive, through the urethra to gain access to the
urinary bladder. The inner bladder can be visualized using camera and
fiberoptics and fluid can be added or subtracted (urine) from the bladder. Also
a small diameter flexible biopsy needle can be inserted through the cystoscope
to take bladder wall tissue samples. These samples are always taken under local
or general anaesthesia. We will only include patients that are already
receiving bladder cystoscopy under general / s[inal anesthesia. The risks of
bladder biopsies are minimal, but it can cause : transient minor bleeding,
transient minor pain and discomfort, and in rare case reports, more severe
bleeding or bladder perforation has been described. Cystoscopy increases the
chance of urinary infections, but this is not an added risk for patients who
are already undergoing a bladder biopsy procedure.