IC/BPS is a complex and challenging clinical syndrome. No universally effective treatment is available for this disease. A treatment regimen based on bladder pathology changes is one of the therapeutic directions for IC/BPS. Glomerulations and Hunner's lesions of the bladder mucosa are typical pathological changes commonly observed with bladder hydrodistention under cystoscopy in patients with IC/BPS, which the ESSIC classifies as type II and III IC/BPS[2]. The IC/BPS guidelines of the AUA recommend surgical removal of ulcers in IC/BPS patients with Hunner’s lesion subtypes[3]. According to studies reported by Payne et al., the average symptom score for IC/BPS patients improved by 76% [6]with electrocautery or removal of Hunner's lesions under cystoscopy. Some researchers have reported that for refractory IC/BPS patients without ulcers, transurethral electrocautery applied to hemorrhage sites after bladder hydrodistention can also effectively relieve clinical symptoms[7]. Surgical removal of bladder mucosal lesions often requires the lesions to be relatively limited. If the range of Hunter's lesions is greater than 25% of the bladder mucosal area, then surgical removal is not a suitable treatment option[8]. Regardless of whether electrical resection, electrocautery or laser ablation is performed, potential complications such as bladder perforation and digestive tract injuries may occur, and a larger range of bladder mucosal cauterization may also cause bladder contracture.
Although the etiology of IC/BPS is still unclear, autoimmunity is recognized as one of the main causes of IC/BPS[9]. Supporting evidence demonstrates similar gender and age distributions among IC/BPS patients to those of patients with known autoimmune diseases, and the clinical features of IC/BPS are similar to those of other established autoimmune diseases[10]. Immunosuppressive drugs routinely used to treat autoimmune diseases have yielded positive results in specific IC/BPS patients[11, 12], which also confirms that autoimmunity plays a key role in IC/BPS. Mast cell activation with the release of inflammatory mediators interacting with other inflammatory cells and nervous system also revealed an important role of inflammatory response in the pathogenesis of IC /BPS[2, 13, 14]. TA is a long-acting adrenal corticosteroid with anti-inflammatory, anti-itching and vasoconstricting effects. It has strong and long-lasting anti-inflammatory and anti-allergic effects but a weak water-sodium retention effect. TA is inexpensive and extremely well tolerated when used locally. Cox and other researchers pioneered the submucosal TA injection method for the treatment of refractory Hunner’s lesion-subtype IC/BPS patients and reported satisfactory results4. A preliminary study by Rittenberg et al on IC/BPS patients with Hunner's lesions and bladder mucosal fissures also showed that TA contributes to symptom control and improves the quality of life of IC/BPS patients[5].
Based on the positive efficacy of electrocautery or electrical resection of bladder mucosal lesions in patients with type II and type III IC/BPS and the significant alleviation of clinical symptoms observed among type III IC/BPS patients with TA injection, we speculate that this treatment is also suitable for type II IC/BPS patients. Although the incidence of IC/BPS is lower in men than in women, IC/BPS in men is not uncommon in clinical practice and is easily misdiagnosed and mistreated. This study is the first to include male patients with type II IC/BPS, to demonstrate the efficacy of this therapy for Hunner's lesion-subtype IC/BPS and to explore the efficacy of this treatment in males and type II IC/BPS patients. The IPSS is mainly used to evaluate urinary symptoms, is easy to understand and manage, and can easily and intuitively reflect the negative impact of urinary symptoms on quality of life. By comparing the preoperative and postoperative IPSS and PUF scores, nearly 3/4 of the patients were found to have significant pain relief and reduced urinary tract symptoms at 4 weeks after surgery, and their quality of life improved significantly. No perioperative and long-term complications were noted, and the treatment efficacy was comparable to that reported by researchers such as Cox[4]. Furthermore, we found that submucosal injection of TA at hemorrhage sites can also control the symptoms of IC/BPS, and the efficacy was the same as that for type III IC/BPS. Significant effects can also be achieved in male patients. Among the factors influencing the efficacy outcome, patients with an advanced age and higher IPSS and PUF scores were more likely to experience a good response to treatment.
The current study shows that the duration of the treatment effect of simple bladder hydrodistention for IC/BPS is generally less than 6 months, and the duration of the treatment effect of submucosal injection of TA for IC/BPS is not clear. The longest follow-up time in the current study was only 3 months[5]. We performed a follow-up of all patients for at least 1 year, and 43% of the patients had a one-year remission period in terms of symptom control after this treatment. Patients with symptoms recurrence had a similar remission period after reinjection to that after the first injection. Ten patients still showed effectiveness at the time of the last follow-up, and 5 patients had sustained efficacy for more than 2 years. Whether this treatment can fully control IC/BPS symptoms remains to be further determined.
The main limitations of our study include the retrospective analysis, small sample size, and lack of a control group. A good definition of cystoscopic findings at the time of hydrodistention for IC/BPS is beneficial to the selection of treatment and the evaluation of efficacy. We referred to the classification method of ESSIC and showed that the efficacy of submucosal injection of TA at hemorrhage sites was the same as that for Hunner's lesions subtype IC/BPS. Moreover, using the control groups who received saline injections into their lesions or only received bladder hydrodistention may reveal more information on the therapeutic effect of submucosal injection of TA for IC/BPS. Our team will continue to include more patients and better evaluate this treatment using a randomized group control and regular follow-up.