Transurethral Fulguration of Hunner Lesion Was Effective for Primary Management of Pelvic Pain in Patients With Interstitial Cystitis: A Long-Term Follow-Up Study.

Hyun Ju Jeong: data creation, formal analysis, investigation, methodology, writing – original draft, writing – review and editing. Yu Jin Kang: data creation, investigation, methodology, writing – review and editing. Min Soo Choo: supervision, writing – review and editing. Seong Jin Jeong: supervision, writing – review and editing. Seung‐June Oh: conceptualization, data creation, formal analysis, investigation, methodology, supervision, writing – original draft, writing – review and editing.

This study received approval from the Institutional Review Board of visited Seoul National University Hospital (IRB No: 2401‐148‐1506) and was conducted in accordance with the Declaration of Helsinki and Ethical Standards set by the Institutional Review Board.

We retrospectively reviewed the electronic medical records of consecutive patients who visited Seoul National University Hospital for pelvic pain suggestive of IC between October 2005 and December 2019. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No: 2401‐148‐1506). Patients were diagnosed with IC through a diagnostic pathway according to published guidelines [ 1 , 4 , 12 , 13 ]. The inclusion criteria were pain or discomfort in the suprapubic, pelvic, urethral, vaginal, or perineal areas perceived to be related to the urinary bladder and concomitant lower urinary tract symptoms with frequency, nocturia, and urgency. The exclusion criteria included age < 18 years, pregnancy, urinary tract infection, symptomatic urethral diverticulum, urinary stone, benign or malignant bladder tumors, gynecological malignancies, radiation cystitis, any significant gynecological disease including ovarian cyst, urogenital prolapse, vaginal candidiasis, pelvic inflammatory disease, endometriosis, adenomyosis, and gynecologic malignancies [ 14 ]. If patients initially visited the hospital with pelvic pain, detailed information on the patient's chief complaint, period from symptom onset, presence or absence of underlying disease, pain location, and medical history were collected. The diagnostic procedure was the same as in our previous paper [ 14 ]. Briefly, physical examination was performed on all patients, and urinalysis, urine culture (UC), uroflowmetry with post‐void residual (PVR) volume measurement, and frequency‐volume chart (FVC) for 3 days [ 15 ] were performed. Urine cytology was performed to determine whether urothelial cancer was present, and for men aged > 50 years, a serum prostate specific antigen test was performed to eliminate prostate cancer. If bacteria were detected in UC at ≥ 10 5 /colony forming unit, antibiotics were administered and reexamined. Tuberculosis (TB) test was performed on urine specimens to determine whether genitourinary TB was present [ 14 ]. Ultrasonography, intravenous pyelography, and computed tomography were performed as imaging studies to eliminate other confusable diseases. If necessary, urodynamic studies were performed [ 16 ]. We screened patients for the need for cystoscopy based on the patient medical history and additional information obtained from FVC, etc. In patients suspected of presumptive ulcerative IC or if other diagnoses including bladder CIS lesion had to be eliminated, observation cystoscopy was performed on an outpatient basis [ 14 ]. If abnormal bladder mucosal lesions suggesting Hunner lesion were found in cystoscopy, the patient was admitted and cystoscopic surgery was performed. The procedure was performed according to the procedure described previously [ 14 ]. Under general or spinal anesthesia, the patient was placed in the lithotomy position, and a 24 Fr rigid cystoscope (Karl Storz SE & Co. KG, Tuttlingen, Germany) was inserted through the urethra. After performing bladder washing cytology, the bladder was carefully observed to identify bladder mucosal lesions, which were mapped and recorded. Thereafter, bladder hydrodistention was performed for diagnostic or therapeutic purposes [ 16 ]. Normal saline was placed 80 cm above the patient's pubic symphysis, and the bladder was filled to the maximum anesthetic bladder capacity, and the hydrodistention was maintained for 8 min before draining. After draining the normal saline, mucosal changes, such as glomerulation, cracks, and fissures, were checked with a cystoscope. Cold cup biopsy was performed on 2–4 representative hyperemic lesions of the bladder that were initially identified before hydrodistension. Bladder tissue samples were immediately stored in formalin glass containers. TUF of the ulcer lesions was performed on the bladder mucosal lesions using a monopolar or bipolar loop resectoscope set (Karl Storz SE & Co. KG, Tuttlingen, Germany). After confusable diseases were initially excluded, follow‐up was performed at 3–4 months intervals on an outpatient basis. During follow‐up, UA, UC, urine TB test, and urine cytology were performed as needed. The patient's subjective pain level was classified into “no pain,” “mild,” “moderate,” and “severe.” The management policy for the patient's pelvic pain was based on the patient's subjective symptom severity on an on‐demand basis. Patients with moderate pain were prescribed analgesics, such as NSAIDs or short‐term opioid analgesics. Patients with no or mild pain were followed without any special treatment. Oral pentosan polysulfate was prescribed, if necessary. If pelvic pain was persistently moderate or severe, the patient was hospitalized and TUF for bladder lesions was performed under general or spinal anesthesia. Rarely, additional bladder hydrodistention was performed, if necessary. If the pain was intractable, cystectomy was performed. If the bladder lesion involved the ureteral orifice, total cystectomy was performed, and if not, supratrigonal cystectomy was performed, followed by urinary diversion or bladder replacement. Pathological examination results were obtained from the resected bladder tissue postoperatively. If patients were regularly followed at 3–4 months intervals postoperatively, the period of repeat procedure was analyzed. The authors assumed that patients would continue to follow up if they continued to have pelvic pain after cystoscopic surgery. Patients who regularly visited the outpatient clinic and re‐underwent cystoscopic surgery were considered treatment failure with TUF (TF‐TUF). Patients who regularly visited the outpatient clinic and received conservative management were considered treatment success with conservative management (TS‐CM). Patients who did not visit the outpatient clinic during this regular interval follow‐up were classified into two categories by reviewing the EMR; patients who had moderate or severe pain during the last visit who no longer visited were defined as follow‐up loss with presumptive treatment failure (TF‐FL), whereas those who had little or mild pain during the last visit were defined as follow‐up loss with presumptive treatment success (TS‐FL). All variables were expressed as means, standard deviations, and percentages. Baseline data were analyzed with descriptive statistics. The period of recurrence was presented with median (interquartile range [IQR]). p ‐value < 0.05 was considered statistically significant. All data were analyzed using SPSS version 27.0 (SPSS, IBM Corp., Armonk, NY, USA).

Patients who visited the outpatient clinic owing to pelvic pain were excluded from confusable diseases through work‐up. A total of 275 patients had ulcerative lesions confirmed on observational cystoscopy. Of the 275 patients, 240 (57 men, 23.7% and 183 women, 76.3%) received initial cystoscopic surgery for ulcerative lesions, including bladder biopsy and TUF for ulcerative lesions, and/or bladder hydrodistention (Table  1 ). Pathological examination of bladder biopsy specimens showed chronic inflammation. If pelvic pain persisted or worsened during the follow‐up period postoperatively, TUF for Hunner lesion was performed (Figure  1 ). Of the 275 patients, three patients visited our hospital because of intractable pelvic pain after cystoscopic surgery at another hospital with all other confusable conditions excluded. One patient underwent cystectomy with bladder replacement and two patients underwent cystectomy with urinary diversion. These patients were excluded from the present analysis. Baseline characteristics in patients with interstitial cystitis ( n  = 240). Note: All variables are presented as mean ± standard deviation or number of patient (%). Abbreviation: PSA, prostate specific antigen. Flowchart for clinical pathway for IC/BPS. The period of recurrence is presented with median (IQR). 1 There are two patients who underwent bladder biopsy at another hospital and received hydrodistention and transurethral fulguration (TUF) of the ulcer as initial cystoscopic surgery at our hospital. The three patients in the dotted box are excluded from the present analysis. Cx, cystectomy; HD, hydroditention; IC/BPS, interstitial cystitis/bladder pain syndrome; IQR, Interquartile range; TF‐FL, follow‐up loss with presumptive treatment failure; TS‐CM, treatment success with conservative management; TS‐FL, follow‐up loss with presumptive treatment success. After initial cystoscopic surgery, TS‐CM was 71 patients (29.6%) and TS‐FL was 56 patients (23.3%), resulting in the overall treatment success of 127 patients (52.9%), whereas TF‐TUF was 64 (26.7%) and TF‐FL was 39 (16.3%), resulting in an overall treatment failure of 103 (42.9%). The median period of recurrence from initial cystoscopic surgery to second TUF was 12.0 (IQR: 6.0–25.0) months. After second TUF, TS‐CM was 15 (23.4%) and TS‐FL was 18 (28.1%), resulting in an overall treatment success of 33 (51.6%), whereas TF‐TUF was 15 (23.4%) and TF‐FL was 10 (15.6%), resulting in an overall treatment failure of 25 (39.1%). The median recurrence period from the second TUF to the third TUF was 12.0 (IQR: 12.0–32.0) months. After the third TUF, TS‐CM occurred in three patients (20.0%) and TS‐FL in six patients (40.0%), resulting in an overall treatment success of nine patients (60.0%), whereas TF‐TUF occurred in five patients (33.3%) and TF‐FL in one patient (6.7%), resulting in an overall treatment failure of six patients (40.0%). Five patients received the fourth TUF. However, only one patient received TUF after the fifth TUF and eventually ended up with cystectomy with ileal conduit. Overall, 18 patients (7.5%) underwent cystectomy (six patients with urinary diversion and 12 patients with cystectomy with bladder replacement) (Figure  2A ). Treatment outcomes after cystoscopic surgery. (A) Treatment success and treatment failure after each cystoscopic surgery. As the number of repeat surgeries increased, the number of patients decreased, indicating that conservative management was successful in controlling pelvic pain; (B) Overall treatment outcome regardless of the number of systoscopic surgeries. Most patients were well‐managed with conservative management. TF‐FL, follow‐up loss with presumptive treatment failure; TF‐TUF, treatment failure with TUF; TS‐CM, treatment success with conservative management; TS‐FL, follow‐up loss with presumptive treatment success. The overall median follow‐up was 21.0 (IQR: 6.0–43.3) months and mean number of TUF was 1.0 (±0.8) per patient. If calculated individually regardless of the number of cystoscopic procedures, the total number of patients whose pain was controlled by conservative management postoperatively, including TS‐FL, was 168 (70.0%). The total number of patients with treatment failure, including those who underwent cystectomy with urinary diversion (six patients)/bladder replacement (12 patients) and TF‐FL, was 72 (30.0%). When the number of patients with follow‐up loss was counted without classifying them into success and failure, the treatment success (TS‐CM)/lost to follow up/treatment failure (cystectomy with urinary diversion or bladder replacement) were 36.3%/56.2%/7.5% (Figure  2B ). For all patients who underwent TUF, the maximum anesthetic bladder capacity (MABC) was investigated at each TUF by reviewing the operative records in the Electronic Medical Record. We examined whether there were statistically significant changes in the MABCs of subsequent TUFs compared with the MABC at the first TUF. The MABCs of patients who underwent TUF 1 to 4 times were 466.5 ± 132.9 mL, 422.8 ± 131.8 mL, 437.5 ± 134.5 mL, and 432.0 ± 169.9 mL, respectively. The MABC significantly decreased as the number of TUFs increased (repeated measures ANOVA, p  = 0.046). After the first cystoscopic surgery, a total of five patients (2.1%) visited the emergency room (ER) due to bleeding and underwent bladder irrigation/transurethral coagulation of the bladder, while one patient (0.4%) visited the ER due to acute urinary retention. After the second surgery, one patient (1.6%) visited the ER for bleeding and received bladder irrigation or transurethral coagulation. From the third to the seventh cystoscopic surgeries, no patients experienced complications.

In this study population, some patients (26.7%; 64 out of 240 patients) had recurrence of pain after initial cystoscopic surgery; however, a similar number of patients (29.6%; 71 out of 240 patients) had well‐managed pelvic pain to a tolerable level. Additionally, the follow‐up loss of patients after initial cystoscopic surgery was 95 patients (39.6%). However, 75 of them (78.9%) had no, mild, or moderate pain postoperatively, indicating that cystoscopic surgery was effective. As the number of cystoscopic procedures increased, the number of patients undergoing cystoscopic procedures decreased significantly, and the number of patients receiving conservative management increased (Figure  2 ). Therefore, we believe that TUF is effective in alleviating pelvic pain in patients with IC and ulcerative lesions. There are a few retrospective studies that have evaluated the effect of electrocautery in patients with IC and Hunner ulcer [ 6 , 7 , 8 ]. In a study by Payne et al. from Wisconsin [ 6 ], 14 patients with IC were followed for an average of 27 months after electrocautery of the Hunner lesion. Twelve patients showed > 50% symptom improvement and eight showed 100% improvement. Four patients had symptomatic recurrence but all improved with repeated endoscopic ablation. This report demonstrated that electrocautery was effective. Nonetheless, the number of patients included in the study was small and the follow‐up period was short, at a maximum of 27 months. Hillelsohn et al. [ 7 ] from New York published the results of a retrospective study of 59 patients with IC with a median follow‐up period of 44 months. In their study, repeat fulguration was required in 45.8% at 12 months and 57.2% at 2 years of follow‐up. Recently, Ko et al. [ 17 ] performed a prospective randomized controlled study comparing the efficacy of the transurethral resection and coagulation of the Hunner lesions in 126 patients. The median period from the initial cystoscopic surgery to the second cystoscopic surgery ranged between 12 months (Ko et al.) [ 17 ] and 14.5 months (Chennamsetty et al.) [ 8 ], which was similar to 12.0 months in our study. These figures are only for patients who experienced recurrence of symptoms after initial cystoscopic surgery. Importantly, there are more patients who do not experience recurrence of symptoms after initial cystoscopic surgery. Since IC is a chronic condition, long‐term follow‐up is essential to obtain accurate information about the natural history of IC, including recurrence of pain. Important facts that cannot be revealed in the above comparative study [ 17 ], covering a relatively short or midterm follow‐up, can be revealed in an observational patient cohort study with a long‐term follow‐up study design. In a maximum 17‐year long‐term study of 76 patients with IC who received TUF with electrocautery by Chennamsetty et al. [ 8 ], 51 patients (67.1%) required subsequent electrocautery. An average of 2.9 electrocautery sessions were required per patient. Notably, there was no decrease in bladder capacity following electrocautery. Additionally, a questionnaire survey was conducted on some part of patients, and 90% of them reported symptom improvement, and 98% of patients would re‐undergo electrocautery, indicating that patient satisfaction with electrocautery was high. The recurrence rate of the above long‐term follow‐up studies [ 7 , 8 ] were higher compared with our study of 26.7% of patients requiring retreatment after initial TUF. It is difficult to explain this difference; however, it is believed to be due to differences in the criteria for determining the need for additional surgery, clinical settings of the patients, and other factors. Above long‐term follow‐up studies demonstrated that TUF for Hunner ulcer was effective and safe in patients with IC. These results were confirmed in our present study with a long‐term follow‐up in 240 patients with IC. For Hunner lesions, TUF is recommended in the guidelines of the American Urological Association. Pelvic pain and lower urinary symptoms were improved after TUF in patients with IC and ulcer [ 6 , 17 ]. Furthermore, TUF can provide high satisfaction in patients with IC and Hunner lesion [ 6 ]. Conversely, the therapeutic effect of HD is limited. There is a lack of high‐level research results on the therapeutic effect of bladder hydrodistension [ 18 ]. Therefore, we believe that TUF of ulcer is effective in patients whose pain is relieved by cystoscopic surgery. The strengths of this study are that it is a long‐term large‐scale patient cohort study. As mentioned, long‐term follow‐up studies are important as IC is a chronic disease. Knowingly, long‐term study results on the treatment of IC are rare [ 9 , 10 , 11 ]. The limitations of our study are that we did not use objective tools, including a visual analog scale to evaluate the severity of pelvic pain or questionnaire specific to IC. This study may have limitations because it is a retrospective study. The study results were conducted in a single center. However, we believe that patient selection bias was minimized by having a single urologist perform consistent diagnostic tests and regular follow‐up observations under a set order protocol of the EMR.

Our study results showed that TUF‐based cystoscopic surgery is an effective basic treatment for pelvic pain management in patients with IC.

The International Continence Society defines bladder pain syndrome (BPS)/interstitial cystitis (IC) as persistent or recurrent chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom, such as an urgent need to void or urinary frequency [ 1 ]. BPS/IC is divided into Hunner type IC and BPS [ 2 ]. Hunner type IC is a case in which a Hunner lesion is observed on cystoscopy [ 2 ]. The treatment of IC is divided into conservative treatment, including behavioral therapy based on pain management, medical treatment, intravesical instillation, hydrodistention, and transurethral fulguration (TUF) of the Hunner ulcer [ 3 , 4 ]. In cases of intractable pelvic pain, cystectomy with urinary diversion or bladder replacement is considered; however, it is inappropriate as a primary pain management method for all patients with IC who underwent major surgery. In cases of moderate or severe pelvic pain that cannot be controlled with medication, minor surgery is required. Some reports have reported that hydrodistention of the bladder [ 5 ] or TUF of the Hunner ulcer are effective in these cases [ 6 , 7 , 8 ]. However, there are relatively few studies on the effectiveness of transurethral surgery for patients with IC. Knowingly, most patients have a short follow‐up period [ 6 , 7 , 8 ], Therefore, reports on natural history that has obtained clinical results by long‐term observation are rare [ 7 , 8 , 9 , 10 , 11 ]. We aimed to analyze the effect of TUF on pelvic pain in a group of patients with IC who experienced actual clinical settings for 15 years.

The authors declare no conflicts of interest.