Increased detrusor collagen is associated with detrusor overactivity and decreased bladder compliance in men with benign prostatic obstruction

Abstract

BackgroundThis study aimed to investigate the relationship between detrusor collagen content and urodynamic parameters in men with benign prostatic obstruction.Material and methodsNineteen consecutive patients undergoing open prostatectomy for bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) were evaluated. Urodynamic tests were performed in all patients. BOO and detrusor contractility were assessed with the BOO index (BOOI) and the bladder contractility index (BCI), respectively. A bladder fragment was obtained during prostatectomy. Eight cadaveric organ donors composed the control group. Bladder sections were stained with picrosirius red and hematoxylin-eosin. The collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with urodynamic parameters was investigated.ResultsSeven (36.8%) patients were operated on due to lower urinary tract symptoms and 12 (63.2%) had urinary retention. The mean prostate volume was 128.6 cm3 ± 32.3 cm3, the mean BOOI was 76.4 ± 33.0, and the mean BCI was 116.1 ± 33.7. The mean C/M in BPH patients and controls were 0.43 ± 0.13 and 0.33 ± 0.09, respectively (P = 0.042). A negative correlation was shown between C/M and bladder compliance (r = –0.488, P = 0.043). The C/M was increased in BPH patients with detrusor overactivity (DO) compared to those without DO (0.490 ± 0.110 and 0.360 ± 0.130, respectively; P = 0.030) and also in patients with urinary retention (P = 0.002). No correlation was shown between C/M and maximum cystometric capacity, BOOI, or BCI.ConclusionMen with BOO/BPH have increased detrusor collagen content which is associated with decreased bladder compliance, detrusor overactivity, and urinary retention.

Progressive bladder remodeling due to bladder outlet obstruction: a systematic review of morphological and molecular evidences in humans

“…Detrusor ECM remodeling is characterized by increased accumulation of collagen and elastic fibers in both the interfascicular and intrafascicular compartments. This finding has been confirmed in several studies using both light and electron microscopy techniques [ 10 , 11 , 15 – 21 ]. Interestingly, Gilpin et al found that patients with evidence of interfascicular connective tissue infiltration had the highest levels of SMCs mean profile area thus leading the authors to hypothesize that the deposition of connective tissue occurs at a later stage with respect to onset of SMCs hypertrophy [ 10 ].…”

“…Although BOO was not a predictor of increased collagen deposition, patients with reduced bladder compliance and those with a PVR ≥ 200 mL showed a significantly higher C/M [ 20 ]. Similarly, Bellucci et al found a significant negative correlation between C/M and bladder compliance [ 21 ]. Moreover, the probability of urinary retention increased significantly with the C/M.…”

“… Holm, 2003 [ 22 ] Case control 25 • Significant correlation between intra- and interfascicular elastin and BOO degree Mirone, 2004 [ 15 ] Case control 36 • ↑collagen content in BPO patients with respect to controls • ↑collagen content in patients with severe symptoms Horn, 2004 [ 44 ] Observational 54 • Correlation between abnormal morphology and impaired bladder compliance and decreased capacity Collado, 2006 [ 11 ] Case control 33 • ↑ intrafascicular and interfascicular collagen • ↑ intrafascicular fibrosis in BOO patients with history of AUR • ↑ SMCs diameter in BOO patients with respect to controls • Not significant differences in terms of SMCs diameter between BOO patients with and without AUR history • Positive correlation between SMCs diameter and symptoms duration Rubinstein, 2007 [ 18 ] Case control 10 • ↑ collagen and elastic fibers Blatt, 2012 [ 16 ] Case control 17 • Poor post-TURP voiding outcome in patients with detrusor ultrastructural pattern characterized by variable muscle cell size, muscle cell shape, abnormal fascicle arrangement and collagenosis. Bellucci, 2017 [ 21 ] Case control 19 • ↑ C/M • Significant negative correlation between C/M and bladder compliance • Significant correlation between the probability of urinary retention and C/M Averbeck, 2017 [ 20 ] Observational 38 • ↑ C/M in patients with PVR ≥ 200 mL and in those with reduced bladder compliance AUR acute urinary retention, BOO bladder outlet obstruction, C/M connective tissue-to-smooth muscle ratio, PVR post void residual volume, SMCs smooth muscle cells, TURP trans urethral resection of the prostate …”

Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL‑1β and the SGK1‑NFAT2 signaling pathway

“…Bladder remodeling induced by Boo leads to impaired storage and emptying of the bladder, which is characterized by increased collagen accumulation (41,42). increased collagen deposition in the ecM is a key reason for decreased compliance (43,44). Previous studies have reported that pressure promotes an increase in ecM production around BSMcs (45,46).…”

MicroRNA‐101 protects bladder of BOO from hypoxia‐induced fibrosis by attenuating TGF‐β‐smad2/3 signaling

“…After BOO, the contractile and nonproliferative phenotype of the BSMCs may transform to a state of synthetic phenotype, results in altered BSMC/ECM interactions, which cause a loss of contractility of BSMCs. Altered ECM composition, especially, Collagens I, III, has been reported in the hypertrophic bladder during the fibrotic stage of hypertrophy .…”