Clinical Features and Histologic Findings in Bladder Pain Syndrome/Interstitial Cystitis
Condition: Interstitial Cystitis, Chronic; Painful Bladder Syndrome
MeSH terms: Cystitis; Cystitis, Interstitial; Syndrome
Study type: Observational [Patient Registry]

Summary: 
      Objectives- to find out whether a correlation exists between denudation of urothelium and
      diagnosic delay in patients with BPS / IC, secondary aim was to search a correlation between
      impact of symptoms evaluated with ICSI-ICPI and number of comorbid conditions associated with
      BPS-IC.

      Patients and Methods- Fifty-seven consecutive patients underwent cystoscopy under anaesthesia
      to classify those cases suspected of BPS/IC. As for the evaluation of the ICSI-ICPI scores we
      considered significant relevant values those ≥ 12. Patients underwent cystoscopy with
      hydrodistension under general (90%) or locoregional anaesthesia. Bladder biopsies were taken,
      including detrusor muscle, from those areas with the most apparent bladder wall lesions. All
      biopsies were then fixed in 4% formalin and sent to the Pathologist for examination.
    

Detailed description: 
      Between 2005 and 2016, in our Department 57 consecutive patients underwent cystoscopy under
      anaesthesia to classify those cases suspected of BPS/IC. Patients reported long-lasting
      irritative bladder symptoms, including urgency, daytime frequency of seven or more episodes,
      nocturia, and pain in the lower abdomen, lower back, vagina or perineum during filling or
      after micturition. Alternative diagnoses such as urinary tract infection (UTI) were excluded.
      Confusable diseases were ruled out by thorough history, clinical examination, urine analysis
      and imaging.

      By means of a detailed medical history we considered the time of symptom onset, frequency of
      micturitions, the presence of associated diseases. All patients were given the same
      questionnaire (O'Leary-Sant Interstitial Cystitis Symptom and Problem Index) (19), filled at
      the time of bladder biopsy.

      As for the evaluation of the ICSI-ICPI scores we considered significant relevant values those
      ≥ 12.

      All patients underwent cystoscopy with hydrodistension under general (90%) or locoregional
      anaesthesia. A rigid cystoscope with a Ch. 22 caliber was used, mannitol solution was used as
      filling fluid, and infusion height was 80 cm above the symphysis pubis. During filling the
      bladder was continuously inspected. At maximal capacity, distension was maintained until
      spontaneous filling stopped and maximum capacity was reached. At this point the bladder was
      drained and bladder walls and mucosa were closely examined . The bladder was then filled
      again at approximately half capacity, and at least three deep biopsies were taken, including
      detrusor muscle, from those areas with the most apparent bladder wall lesions.

      All biopsies were then fixed in 4% formalin and sent to the Pathologist for examination. It
      was specifically asked to assess the presence of urothelial denudation, inflammatory
      infiltrate, counts of mast cells in the submucosa and detrusor, presence of intrafascicular
      fibrosis and submucosal bleeding. A cut-off of 28 mast cells / mm2 was used for the
      assessment of detrusor mastocytosis.

      Morphologic Study Biopsy samples were cut in 5-μm-thick sections, then stained with the
      following reagents for morphologic evaluation: Hematoxylin-Eosin, Giemsa and Masson Tricromic
      Stain. This procedure was performed by automatic stainers (Leica, mod. ST5020 and mod.
      Autostainer™ XL).

      In each biopsy the following parameters were evaluated, according to the recommendations
      reported by Hanno et al. (20) and reported in Table 1.

      If the biopsy wasn't adequately sized (< 1 mm2-wide), we decided to evaluate the most
      reliable parameters, giving a N.V. (Not Valuable) response to the others.

      Such parameters were single-blindly studied by two independent pathologists using optic
      microscopes (Nikon, mod. Eclipse™ E400 and mod. Eclipse™ CI) and discordant cases were then
      discussed jointly.

      Immunohistochemical Studies Immunohistochemical reactions with Dako monoclonal antibody
      anti-Human Mast-cell Tryptase (Clone AA1; IgG1, Kappa), at 1:4000 dilution, were performed in
      order to highlight the mast-cell component of the inflammatory infiltrate, and then to
      quantify it. According to the protocol followed at the Laboratory of Immunohistochemistry of
      the Pathology Unit the automatic immunostainer Dako Omnis™ was used.

      Evaluation of the Immunostainings

      The reactions were evaluated using optic microscopes (Nikon, mod. Eclipse™ E400 and mod.
      Eclipse™ CI). The following parameters were studied:

        -  Number of mast-cells/mm2 of mucosa;

        -  Number of mast-cells/mm2 of submucosa;

        -  Number of mast-cells/mm2 of the detrusor layer. In order to obtain the highest accuracy,
           a single-blind evaluation was performed by two independent pathologists; discordant or
           uncertain cases were then discussed jointly.

      All patients were evaluated retrospectively using patient files, they were given a score
      between 0 to 5 according to the presence of the following criteria (each criteria counting
      one point): pain, nocturia, a bladder capacity of 500 mL, glomerulations, or interfascicular
      fibrosis.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Probability Sample
Study population: 
        Fifty-seven consecutive patients underwent cystoscopy under anaesthesia to classify those
        cases suspected of BPS/IC
      
Biospecimen description: 
      bladder biopsy