Abstract

To establish whether the urothelial ulceration observed in ketamine-induced cystitis is triggered by urinary or systemic factors. This was achieved with a rare case where an urachal cyst was found near the bladder dome in a patient undergoing cystectomy for unremitting pain following ketamine abuse. Clinical investigations included cystoscopy, video urodynamic investigation, and computed tomography of the kidneys, ureters, and bladder. Histological staining was combined with immunoperoxidase labeling for markers of transitional epithelial differentiation. The urachus found near the dome of the bladder was observed to be a separate cyst, with no evidence of patency found during surgery or video urodynamic investigation. The urachus was lined by a mildly reactive metaplastic epithelium of mixed transitional and columnar morphologies. Evidence of widespread cytokeratin 13, basal p75(NTR), and sparse superficial uroplakin 3a immunoreactivity suggested the urachal epithelium was fundamentally transitional in nature. Near total loss of bladder urothelium was observed from regions in contact with urine, whereas the urachal epithelium (not exposed to urine) remained healthy. This study supports the hypothesis that urinary (and not systemic) factors are the main driver of urothelial ulceration in ketamine-induced cystitis. The most likely excreted factors responsible are ketamine and potentially its metabolites. This study reinforces the importance of complete cessation of ketamine use in patients with ketamine-induced cystitis.

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