A Rare Urachal Cyst in a Case of Ketamine-induced Cystitis Provides Mechanistic Insights

doi:10.1016/j.urology.2015.12.015

Urology

Volume 90, April 2016, Pages 223.e1-223.e7

https://doi.org/10.1016/j.urology.2015.12.015 Get rights and content

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Section snippets

Clinical Investigations

Preliminary investigations included blood tests: full blood count, urea and electrolytes, and liver function tests (including γ-glutamyl transpeptidase). Urinalysis was performed by microscopy, culture, and sensitivity, with additional cytological analysis. The urinary tract was imaged by ultrasound scan, which demonstrated a normal upper urinary tract (data not shown), and computed tomography of the kidneys, ureters, and bladder. The bladder was further studied by cystoscopy and video

Results

In this study we report a 30-year-old male with an 8-year history of ketamine abuse peaking at several grams per day. Urinary frequency was debilitating, with a painful urge to void every 30 minutes and persisting through the night. The full blood count and urea and electrolytes analysis did not reveal any abnormality. All the liver function markers were in the normal range apart from γ-glutamyl transpeptidase. Over a 5-year period, the patient's γ-glutamyl transpeptidase activity was monitored

Comment

KIC is a relatively new disease entity for which little is known about the pathological process that leads to the destruction of the urothelial lining of the bladder. The retention of urothelium within the urachus and loss of bladder urothelium observed in this case suggest that direct ketamine (or metabolite) exposure via the urine is responsible for driving the pathology through destruction of the urothelium. Previously, it had been suggested that systemic exposure might play an important

Conclusion

This case study supports current conservative clinical practice for KIC where cessation of ketamine use must be the immediate priority; however, the justification for cystectomy in this patient was verified by a near total loss of urothelium from the whole bladder. Urothelium was retained within the urachal cyst and lost in the bladder, suggesting that direct ketamine/metabolite exposure via the urine, rather than systemic factors, was responsible for driving the urothelial ulceration. Future

References (21)

R. Shahani et al.
Ketamine-associated ulcerative cystitis: a new clinical entity
Urology
(2007)
M.C. Parkin et al.
Detection of ketamine and its metabolites in urine by ultra high pressure liquid chromatography-tandem mass spectrometry
J Chromatogr B
(2008)
L. Muetzelfeldt et al.
Journey through the K-hole: phenomenological aspects of ketamine use
Drug Alcohol Depend
(2008)
B.E. Leiby et al.
Discovery of morphological subgroups that correlate with severity of symptoms in interstitial cystitis: a proposed biopsy classification system
J Urol
(2007)
ChenY.C. et al.
Ketamine-associated vesicopathy
Q J Med
(2012)
LaiY. et al.
Ketamine-associated urinary tract dysfunction: an underrecognized clinical entity
Urol Int
(2012)
J.D. Oxley et al.
Ketamine cystitis as a mimic of carcinoma in situ
Histopathology
(2009)
S.C. Baker et al.
Nerve hyperplasia: a unique feature of ketamine cystitis
Acta Neuropathol Commun
(2013)
D. Wood et al.
Recreational ketamine: from pleasure to pain
BJU Int
(2011)
ChuP.S. et al.
The destruction of the lower urinary tract by ketamine abuse: a new syndrome?
BJU Int
(2008)

There are more references available in the full text version of this article.

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: Financial Disclosure: The authors declare that they have no relevant financial interests.

: Contribution: EK and SCB performed the laboratory experiments and prepared the manuscript. SF was clinical lead on the case. SF, MG, SCB, and JS supervised the research and prepared the manuscript.

: Patient Consent: Consent was obtained under Northern and Yorkshire NHS Research Ethics Committee approval 10/H0903/43.

: Provenance and Peer Review: Not commissioned; internally peer reviewed.

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Basic and Translational ScienceA Rare Urachal Cyst in a Case of Ketamine-induced Cystitis Provides Mechanistic Insights

Objective

Methods

Results

Conclusion

Section snippets

Clinical Investigations

Results

Comment

Conclusion

Urology

J Chromatogr B

Drug Alcohol Depend

J Urol

Ketamine-associated vesicopathy

Q J Med

Ketamine-associated urinary tract dysfunction: an underrecognized clinical entity

Urol Int

Ketamine cystitis as a mimic of carcinoma in situ

Histopathology

Nerve hyperplasia: a unique feature of ketamine cystitis

Acta Neuropathol Commun

Recreational ketamine: from pleasure to pain

BJU Int

The destruction of the lower urinary tract by ketamine abuse: a new syndrome?

BJU Int

Basic and Translational Science
A Rare Urachal Cyst in a Case of Ketamine-induced Cystitis Provides Mechanistic Insights