Urothelial dysfunction and chronic inflammation in patients with bladder outlet obstruction and different bladder dysfunction and different BOO degree
Cheng-Ling, Lee; Hann-Chorng Kuo
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
Bladder outlet obstruction (BOO) may be induced by a wide range of functional and/ or anatomic causes. The resulting obstruction frequently produces bothersome lower urinary tract symptoms (LUTS) in patients. The underlying mechanisms responsible for the bladder dysfunction in BOO remain poorly understood. The purpose of this study is to investigate the urothelial dysfunction and chronic inflammation in patients with BOO.
Materials and Methods:
In this prospective study, we enrolled those patients who presented with LUTS and underwent urodynamic study (VUDS) for further evaluation. Based on their VUDS performances, it was categorized into 4 sub-groups: control, BOO with detrusor overactivity (DO), BOO with Detrusor underactivity (DU) and BOO with hypersenstivity bladder (HSB). Bladder tissues taken from these patients were analyzed. Immunofluorescence (IF) staining of junction protein E-cadherin, mast cell, TUNEL and Zo-1 were performed. The fluorescence intensity of E-cadherin was measured using an Image J method. The percentage of activated mast cells and apoptotic cells were measured and quantified as positive cells per area unit (4 μm2). The numbers of positive protein were correlate with VUDS parameters.
A total of 44 men were enrolled in this study. There were 34 patients presented with BOO (DO: 12, DU: 11 and HSB: 11). The expression and cellular location of E-cadherin, mast cell, TUNEL and Zo-1 were illustrated in Fig.1. The distribution of E-cadherin is significantly reduced in BOO with DU (8.37±9.50) (p<0.000), whereas exhibit highest number of TUNEL (3.60±3.43) (p<0.021) . The tryptase signal in BOO with DO is significantly increased (19.05±6.14) (p<0.000). All these parameters do not show positive correlation with Abrams–Griffiths (AG) number. Increasing number of E-cadherin is associated with Pdet and Qmax. Tryptase/ mast cell is positively associated with FSF.
In this study, we have shown that LUTS secondary to BOO are associated with chronic urothelial inflammation and urothelial dysfunction. DU induced by BOO is associated with significant urothelial defection. This may imply that the loss of functional protein and urothelial cell apoptosis might contribute to the pathophysiology of bladder dysfunction in BOO.