Kwang Jin Ko

Background: Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. Methods: This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. Results: The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. Conclusion: Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.

Interstitial cystitis/bladder pain syndrome (IC/BPS) presents a significant challenge for urologists in terms of management, owing to its chronic nature and adverse impact on patient quality of life. Given the potential distinction between two disease entities within IC/BPS, namely Hunner‐type IC and BPS without Hunner lesion, there is a need for an optimal therapeutic approach that focuses on the bladder lesions in Hunner‐type IC. In cases where Hunner lesions are observed, complete transurethral ablation of these lesions should be prioritized as the initial intervention, as it has demonstrated effectiveness in symptom control. However, recurrence remains a limitation of this intervention. The techniques of resection and coagulation are equally effective in terms of symptom relief and recurrence prevention. Reconstructive surgery becomes necessary in cases of end‐stage IC/BPS where various therapeutic approaches have failed. Patient selection is crucial in reconstructive surgery, particularly for patients with clear Hunner lesions and small bladder capacity who have not responded to previous treatments. Furthermore, it is vital to consider the patients' expectations and preferences adequately. Based on a comprehensive review of the literature and our own clinical experiences, subtotal cystectomy followed by bladder augmentation is considered a safe and effective surgical option. This stepwise and tailored therapeutic approach aims to optimize patients' quality of life by specifically targeting Hunner‐type IC.