Evaluation of Urethral Stricture Tissue Protein Expression Profiles as Predictors of Stricture Recurrence
Alison Levy, MD; Matthew J. Moynihan, MD; MPH; Jennifer Bennett, MD; Travis Sullivan, MS, Kristian Stensland, MD; MPH; Brendan Browne, MD; Ariel Fredrick, MD; Kimberly Rieger-Christ, PhD, Alex J. Vanni, MD
Lahey Clinic, Burlington, MA
BACKGROUND: Urethroplasty is a well supported and efficacious treatment option for male urethral stricture disease. Despite appropriate operative technique, there is a risk of stricture recurrence following urethroplasty that is extremely difficult to predict. Utilizing urethral tissue samples of patients undergoing urethroplasty, we sought to determine both predictors of stricture recurrence and potential protein expression profiles that differentiate patients who develop recurrent disease.
METHODS: Urethral tissue samples from patients undergoing urethroplasty for stricture disease at a single institution were collected. A tissue microarray was created with cores from each sample and immunohistochemical analysis was performed for markers of inflammation, infection, cell cycle disruption, hormone receptor expression, and angiogenesis/oxidative stress. Additionally, patient demographic, stricture characteristics, and clinical follow up data was collected. Data were compared using statistical R software with significant of alpha=0.05.
RESULTS: A total of 81 subjects were included in this study. Mean stricture length was 6.6 cm. Fifty-eight patients (72%) had pathologically confirmed lichen sclerosus. Patients who had a stricture recurrence were significantly more likely to have a history of smoking (p=0.017) and higher BMI (34.3 vs 31.3, p=0.0036). Strictures that recurred demonstrated significantly higher levels of VEGF (p<0.001). Expression of all other proteins did not discriminate those who would progress to recurrence from those who would not.
CONCLUSIONS: Urethral stricture recurrence after urethroplasty is more likely among those with higher BMI and history of smoking. To our knowledge, this is the first study to demonstrate that VEGF expression is higher in patients with stricture recurrence. This suggests the importance of ensuring repairs have adequate blood supply to heal properly. Further investigation of the biochemical properties of recurrent urethral strictures is vital to improve patient selection, counseling, and potentially improve treatment.
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