Participants in this study are part of a larger prospective cohort study performed between July 2015 and June 2017 in a university setting. Patients scheduled to undergo elective gynecological procedures, such as but not limited to excision of endometriosis, ovarian cystectomy, hysterectomy for benign indications, and laparoscopic myomectomy, all of which included either cystoscopy or CWHD, were approached in the pre-operative area to participate. Participants were consented for CWHD as opposed to diagnostic cystoscopy at the time of their procedure.
Inclusion criteria for the large prospective study were as follows: females at least 18 years in age who presented for benign gynecologic procedures. All women eligible for inclusion were initially scheduled for procedures that included either cystoscopy or CWHD, under anesthesia. Patients had to be able to provide informed consent. Exclusion criteria for the study were as follows: pregnancy at time of study, planned cystotomy, incidental cystotomy at time of surgery, age > 90, history of pelvic radiation, and previous or newly diagnosed bladder tumor. While tobacco users were included in the large cohort, we excluded smokers from this study, because of its reported association with IC/BPS and with cystoscopic findings7–9.
After obtaining consent, participants completed a series of questionnaires including the IC Problem Index (ICPI), IC symptom Index (ICSI), Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF), Irritable Bowel Syndrome (IBS) questionnaire. This study specifically examined ICSI scores, because it provides a representation of the burden of urologic symptoms over the previous thirty days. The ICSI has 4 questions, with answers on a scale from 0-5, with 0 representing asymptomatic and 5 representing maximally symptomatic. The four questions address the following bladder symptoms over the previous month: urgency, frequency, nocturia, and pain/burning. Participants were also asked to complete surveys regarding prior medical and surgical history, demographics, and smoking status.
CWHD was performed in a standardized manner: all were performed with a 5 mm 30- or 70-degree cystoscope, with sterile saline used as distending fluid. Fluid bag was placed to gravity 80-100 cm above the patient. After 200 cc, the infusion was stopped and a survey of the bladder was performed. A minimum of two pictures were taken, one of the bladder base and one of the dome of the bladder. Hydrodistension was then performed to gravity, 80-100 cm above the bed level and bladder was filled to either capacity (documented) as determined by either leakage per the urethra or inability to further infuse fluid, or when 700 cc was reached. Once the bladder was filled, it was then emptied within 60 seconds. At least five images were obtained: trigone, left bladder wall, right bladder wall, posterior bladder wall, and dome of the bladder.
Images were de-identified, batched in sets from 25 participants, and evaluated by a panel of 3 urogynecologists. Glomerulations were graded by distribution and number on a predetermined scale that was developed for this research project. The scale used in our analysis is as follows; > 10 glomerulations in 3-4 quadrants, > 10 glomerulations in 1-2 quadrants, glomerulations occurring at a lower rate, or no glomerulations.
Women who met the criteria for being minimally symptomatic or highly symptomatic were included in this study. Minimally symptomatic women were defined as women with a score of either 0 or 1 in all subscores of the ICSI, for a maximal score of 4. Participants were also excluded from the minimally symptomatic cohort if they were originally scheduled for cystoscopy with hydrodistention rather than cystoscopy or if they had a history of IC/BPS; these patients were excluded because regardless of their current symptoms, original scheduling for CWHD signaled that a physician had diagnosed IC/BPS. Highly symptomatic women were defined as women with a composite ICSI score of 12 or greater as well as with a score of 4 or 5 to the question: “Have you experienced pain or burning in your bladder?” We included the criteria of a pain/burning ICSI subscale score of 4 or greater, as we chose to focus on women with a high irritative symptom burden. No women with intermediate symptoms identified as part of the larger prospective study were included in this study.
The primary outcome of this study was any glomerulations. Univariate associations were evaluated with Chi-square tests. Pairwise comparisons and subgroup analyses were carried out using Chi-square tests or Fisher’s exact test. Secondary outcomes examined the demographics and medical history of our study groups. A power analysis was not performed prior to initiation of the study, as the cohorts examined in this study are part of a larger prospective study and all participants meeting criteria were included. A threshold P-value of .05 was designated statistically significant.
A sub-analysis was performed to evaluate women with either no glomerulations or >10 glomerulations in 3 or 4 quadrants. Multivariable logistic regression was performed on the population in the subgroup analysis. Given the low event rate in the sub-analysis group, a series of logistic regressions were carried out in order to avoid over-fitting our model. The variables included in our model were minimal symptomatology, self-reported gastroesophageal reflux disease (GERD), recurrent urinary tract infection (rUTI), and history of endometriosis. All analyses were performed using SPSS version 23.0 for Windows (IBM, Armonk, New York).
This study was submitted to and approved by the St. Louis University IRB. It was conducted in accordance with relevant guidelines and regulations as outlined by the St. Louis University IRB and incompliance with the Declaration of Helsinki.