Histopathological classification of ketamine related cystitis in different bladder condition and the association with treatment outcome

Purpose: Ketamine related cystitis (KC) is an emerging clinical syndrome characterized by severe bladder pain and small bladder capacity in the patients with history of ketamine abuse, but the actual pathophysiology is still unclear. Most previous case reports had revealed inflammation cells infiltration with urothelium denudation in the KC bladders. However, a comprehensive study of histopathology findings of KC bladders is still lacking.We review the histopathology findings of the KC bladder and its correlation with clinical symptoms

Materials and Methods: KC patients who were admitted to our hospital were recruited. All patients had intractable urinary tract symptoms which were failure to conservative treatment and were scheduled for supratrigone partial cystectomy with augmentation enterocystoplasty. The abuse history, visual analogue scale (VAS) pain score, cystometric bladder capacity (CBC) maximal bladder capacity under anesthesia were recorded. The bladder speciment taken from partial cystectomy were sent to our pathology department. The specimen were classifed to 4 area, including mucosa, submucosa, muscle and subserosa layer. A 4-point scale (0-none, 1-mild, 2-moderate and 3-severe) was used to grade submucosa neutrophil, eosinophil, lymphocyte, plasma cells infiltration and nerve hyperplasia. The muscle and subserosa layer were also examined for inflammatory cell infiltration, fibrosis and nerve hyperplasia. The ureter specimens taken from ureteral reimplantation were also sent to histopathology review. The clinical symptoms and objective parameters were also correlated with the histopathology finding.

Results: A total of 26 bladder specimens and 4 ureter specimens were reviewed. Mucosa denudation was noted in most bladder specimens, and only 3 bladders (11.5%) had intact urothelium. Inflammatory cells infiltration and nerve hyperplasia were involved in all layers of bladder. Fibrinoid necrosis in submucosa was also found in 4 patients (15.4%). The history of ketamine abuse, VAS, CBC and MBC between all kinds of histopathology finding grades did not have significant difference (all p>0.05). Cessation of ketamine for 3 month also was not associated with inflammation or nerve hyperplasia severity. Ureteral inflammation, nerve hyperplasia and fibrosis were also noted in all layers

Conclusion: Long term ketamine abuse could induce all layers inflammation, nerve hyperplasia and fibrosis in the bladders and ureters. Cessation ketamine for 3 months were not enough for inflammation and nerve hyperplasia recovery in the KC bladder.