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. All of the 8 male patients in our study had been diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in the past and the therapeutic effect aimed at CP/CPPS with antibiotics, alpha-blockers and other phytotherapeutic agents was poor. For one patient with the symptom of dysuria, concomitant bladder-outlet obstruction was also considered. The maximum flow rate was 11ml/s with urinary volume 95ml and the obstruction was ruled out by pressure-flow study with normal result. These male patients complained with pelvic region pain during the urine storage period which could be relieved after urination. The pain is different from CP/CPPS pain, which is usually located in the perineum, penis, testicles or suprapubic region, and often worsens by urination or ejaculation. They were diagnosed with IC/BPS finally. Because the symptoms also could not be relieved by oral taken of amitriptyline. they were enrolled in the study. 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. Although the time of symptom relief we reported was obviously longer than simple bladder hydrodistention, the efficacy of hydrodistension can’t be ignored. We are aiming at performing a prospective, randomized control study with the groups who will receive saline injections or only bladder hydrodistention at present. The study will reveal more information on the therapeutic effect of submucosal injection of TA for IC/BPS in the future. In addition, The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network findings[15, 16] indicate that specific clinical factors that are easy to measure – including the pain beyond the pelvis, the presence of nonurological chronic overlapping pain conditions (COPCs) and the severity of bladder-focused symptoms (particularly pain with bladder filling) – have a significant impact on symptom trajectories over time. All the enrolled patients in our study were excluded from COPCs including fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome. However, two patients showed diffuse pain preoperatively and the duration of symptom relief was relatively short after the treatment. More detailed clarification of the location of pelvic pain and of possible concomitant non-urological-associated symptoms according to MAPP consensus should also be considered in the future research.