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MP81-02 ABNORMAL SENSORY PROTEIN EXPRESSION AND UROTHELIAL DYSFUNCTION IN HUMAN KETAMINE RELATED CYSTITIS
THE JOURNAL OF UROLOGYâ
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at 37 C. After a stabilization period, permeability was assessed electrophysiologically via transepithelial resistance (TEER) and via the flux of a macromolecular marker (fluorescein isothiocynate-dextrin [FITC4 KD). RESULTS: Compared to saline-treated controls, TNBS-treated rats showed a significantly (P<0.05) higher DAI on days 1 and 3. Exposing the colon to TNBS induced marked colonic damage, but no bladder damage as defined histologically. We found that in response to acute colonic damage, bladder TEER significantly decreased after 1 day (P<0.0001) and after 3 days (P<0.0001), and bladder macromolecular permeability significantly increased after 1 day (P<0.05) and 3 days (P<0.01) when compared to saline-treated controls. In the colon from TNBS-treated rats there was a significant decrease in TEER, and a significant increase in macromolecular transport of FITC-dextrin after 1 day (P<0.005) and 3 days (P<0.0001) compared to saline-treated controls. CONCLUSIONS: These data demonstrate that following acute colon damage there was a marked increase in the permeability of the bladder in the absence of any histological damage to the bladder. This new data reinforces the notion that changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may be important in the overlapping symptomology of PBS and IBS. Source of Funding: P20 DK097799 to RH
MP81-02 ABNORMAL SENSORY PROTEIN EXPRESSION AND UROTHELIAL DYSFUNCTION IN HUMAN KETAMINE RELATED CYSTITIS Yao-Chou Tsai*, New Taipei City, Taiwan; Jia-Fong Jhang, Hsiu-Chen Huang, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Ketamine cystitis (KC) is characterized by severe bladder pain, urinary frequency, decreased bladder capacity and possible upper urinary tract deterioration. Previous animal study suggested urothelial dysfunction and abnormal sensory protein expression might participate in the pathogenesis of KC. Current study is designed to investigate the urothelial dysfunction and sensory protein expressions in human KC bladders. METHODS: The patients with KC who were admitted for cystoscopic hydrodistention or partial cystectomy with augmentation enterocystoplasty were enrolled. Bladder biopsies were taken from 29 patients during cystoscopic hydrodistention. The specimens were investigated for E-cadherin, zonula occludens-1 (ZO-1), tryptase and TUNEL with immunofluorescence staining and quantification. Sixteen bladder specimens obtained from partial cystectomy tissues were investigated for muscarinic receptors M2, M3, TGF-beta, eNOS and P2X3 by Western blotting. Ten healthy control bladder specimens were also investigated and compared with KC bladder. The symptoms, duration of ketamine abuse and urodynamics examination parameters in the KC patients were also analyzed. RESULTS: The KC bladder specimens showed significantly lower expression of E-cadherin and ZO-1, and higher expressions of TUNEL and tryptase activity than the control bladder specimens (Fig. 1 and Table 1). M3 expression in KC bladder was also significantly increased than that in controls. The expressions of M2, eNOS, P2X3 did not show difference between KC bladders and controls. The ketamine abuse history, visual analogue scale pain score, cystometric bladder capacity and maximal bladder capacity under anesthesia did not have significant correlation with the expressions of M2, M3, eNOS and P2X3. CONCLUSIONS: KC bladder tissue showed severe urothelial dysfunction, mast cell mediated inflammation, increased urothelial cell apoptosis and increased muscarinic receptor M3 expression. These findings might explain the clinical symptoms and pathogenesis of KC.
Vol. 193, No. 4S, Supplement, Tuesday, May 19, 2015
Table 1 Functional protein expressions in the KC and control bladders Normal (N¼10)
KC (N¼29)
P-value
TUNEL
0.080.26
3.632.38
0.000
Mast cell
1.251.15
8.755.69
0.000
E-cadherin
42.4116.73
13.8615.74
0.000
ZO-1
11.025.66
3.644.77
0.000
M2
0.120.21
0.180.21
0.314
M3
0.140.93
0.800.46
0.034
P2X3
0.090.13
0.070.09
0.576
eNOS
1.300.16
1.420.78
0.911
KC: ketamine cystitis; ZO-1: zonula occludens-1
Source of Funding: none
MP81-03 PREDICTIVE FACTORS FOR A SUCCESSFUL ONABOTULINUMTOXINA INJECTION TREATMENT FOR REFRACTORY INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME Yuh-Chen Kuo*, Taipei, Taiwan; Dong-Ling Tang, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Although intravesical injection of onabotulinumtoxinA (BoNT-A) has been proved to be promising in treating patients with interstitial cystitis/bladder pain syndrome (IC/BPS), what kind of patients may benefit from this treatment modality remains unclear. We conducted this study to find out the predictors for a successful treatment outcome. METHODS: Patients with IC/BPS who failed conventional treatments were prospectively enrolled. They underwent intravesical injection of 100 U of BoNT-A immediately followed by cystoscopic hydrodistention under intravenous general anesthesia. Variables such as O’Leary-Sant symptom and problem indexes (ICSI and ICPI), bladder pain visual analogue scale (VAS), functional bladder capacity (FBC), daily urinary frequency, nocturia and urodynamic parameters were measured at baseline and 6 months after treatment. Global response assessment (GRA) was obtained to evaluate the treatment outcome 6 months after therapy. GRA2 was defined as a successful result. Univariate and multivariate logistic regression analyses were used to identify variables predicting treatment success at 6 months after BoNT-A injection. RESULTS: A total of 101 patients (13 men and 88 women) were enrolled in our study. Significant improvements could be observed in mean ICSI, ICPI, OSS (ICSIþICPI), pain VAS, FBC, frequency, nocturia and GRA at 6 months after BoNT-A injections (Table 1). The successful rate at 6 month after BoNT-A injection was 46/101 (45.54%). In addition, univariate logistic regression revealed significant relationships between the treatment outcome and baseline ICSI, ICPI, OSS, FBC, frequency and urodynamic parameter FD (all p<0.05). However, multivariate logistic regression model showed the baseline ICSI score (odds ratio ¼ 0.770, 95% confidence interval ¼ 0.601-0.989) was the only predictive factor for a treatment outcome. ICSI12 was the most predictive cutoff
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at 37 C. After a stabilization period, permeability was assessed electrophysiologically via transepithelial resistance (TEER) and via the flux of a macromolecular marker (fluorescein isothiocynate-dextrin [FITC4 KD). RESULTS: Compared to saline-treated controls, TNBS-treated rats showed a significantly (P<0.05) higher DAI on days 1 and 3. Exposing the colon to TNBS induced marked colonic damage, but no bladder damage as defined histologically. We found that in response to acute colonic damage, bladder TEER significantly decreased after 1 day (P<0.0001) and after 3 days (P<0.0001), and bladder macromolecular permeability significantly increased after 1 day (P<0.05) and 3 days (P<0.01) when compared to saline-treated controls. In the colon from TNBS-treated rats there was a significant decrease in TEER, and a significant increase in macromolecular transport of FITC-dextrin after 1 day (P<0.005) and 3 days (P<0.0001) compared to saline-treated controls. CONCLUSIONS: These data demonstrate that following acute colon damage there was a marked increase in the permeability of the bladder in the absence of any histological damage to the bladder. This new data reinforces the notion that changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may be important in the overlapping symptomology of PBS and IBS. Source of Funding: P20 DK097799 to RH
MP81-02 ABNORMAL SENSORY PROTEIN EXPRESSION AND UROTHELIAL DYSFUNCTION IN HUMAN KETAMINE RELATED CYSTITIS Yao-Chou Tsai*, New Taipei City, Taiwan; Jia-Fong Jhang, Hsiu-Chen Huang, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Ketamine cystitis (KC) is characterized by severe bladder pain, urinary frequency, decreased bladder capacity and possible upper urinary tract deterioration. Previous animal study suggested urothelial dysfunction and abnormal sensory protein expression might participate in the pathogenesis of KC. Current study is designed to investigate the urothelial dysfunction and sensory protein expressions in human KC bladders. METHODS: The patients with KC who were admitted for cystoscopic hydrodistention or partial cystectomy with augmentation enterocystoplasty were enrolled. Bladder biopsies were taken from 29 patients during cystoscopic hydrodistention. The specimens were investigated for E-cadherin, zonula occludens-1 (ZO-1), tryptase and TUNEL with immunofluorescence staining and quantification. Sixteen bladder specimens obtained from partial cystectomy tissues were investigated for muscarinic receptors M2, M3, TGF-beta, eNOS and P2X3 by Western blotting. Ten healthy control bladder specimens were also investigated and compared with KC bladder. The symptoms, duration of ketamine abuse and urodynamics examination parameters in the KC patients were also analyzed. RESULTS: The KC bladder specimens showed significantly lower expression of E-cadherin and ZO-1, and higher expressions of TUNEL and tryptase activity than the control bladder specimens (Fig. 1 and Table 1). M3 expression in KC bladder was also significantly increased than that in controls. The expressions of M2, eNOS, P2X3 did not show difference between KC bladders and controls. The ketamine abuse history, visual analogue scale pain score, cystometric bladder capacity and maximal bladder capacity under anesthesia did not have significant correlation with the expressions of M2, M3, eNOS and P2X3. CONCLUSIONS: KC bladder tissue showed severe urothelial dysfunction, mast cell mediated inflammation, increased urothelial cell apoptosis and increased muscarinic receptor M3 expression. These findings might explain the clinical symptoms and pathogenesis of KC.
Vol. 193, No. 4S, Supplement, Tuesday, May 19, 2015
Table 1 Functional protein expressions in the KC and control bladders Normal (N¼10)
KC (N¼29)
P-value
TUNEL
0.080.26
3.632.38
0.000
Mast cell
1.251.15
8.755.69
0.000
E-cadherin
42.4116.73
13.8615.74
0.000
ZO-1
11.025.66
3.644.77
0.000
M2
0.120.21
0.180.21
0.314
M3
0.140.93
0.800.46
0.034
P2X3
0.090.13
0.070.09
0.576
eNOS
1.300.16
1.420.78
0.911
KC: ketamine cystitis; ZO-1: zonula occludens-1
Source of Funding: none
MP81-03 PREDICTIVE FACTORS FOR A SUCCESSFUL ONABOTULINUMTOXINA INJECTION TREATMENT FOR REFRACTORY INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME Yuh-Chen Kuo*, Taipei, Taiwan; Dong-Ling Tang, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Although intravesical injection of onabotulinumtoxinA (BoNT-A) has been proved to be promising in treating patients with interstitial cystitis/bladder pain syndrome (IC/BPS), what kind of patients may benefit from this treatment modality remains unclear. We conducted this study to find out the predictors for a successful treatment outcome. METHODS: Patients with IC/BPS who failed conventional treatments were prospectively enrolled. They underwent intravesical injection of 100 U of BoNT-A immediately followed by cystoscopic hydrodistention under intravenous general anesthesia. Variables such as O’Leary-Sant symptom and problem indexes (ICSI and ICPI), bladder pain visual analogue scale (VAS), functional bladder capacity (FBC), daily urinary frequency, nocturia and urodynamic parameters were measured at baseline and 6 months after treatment. Global response assessment (GRA) was obtained to evaluate the treatment outcome 6 months after therapy. GRA2 was defined as a successful result. Univariate and multivariate logistic regression analyses were used to identify variables predicting treatment success at 6 months after BoNT-A injection. RESULTS: A total of 101 patients (13 men and 88 women) were enrolled in our study. Significant improvements could be observed in mean ICSI, ICPI, OSS (ICSIþICPI), pain VAS, FBC, frequency, nocturia and GRA at 6 months after BoNT-A injections (Table 1). The successful rate at 6 month after BoNT-A injection was 46/101 (45.54%). In addition, univariate logistic regression revealed significant relationships between the treatment outcome and baseline ICSI, ICPI, OSS, FBC, frequency and urodynamic parameter FD (all p<0.05). However, multivariate logistic regression model showed the baseline ICSI score (odds ratio ¼ 0.770, 95% confidence interval ¼ 0.601-0.989) was the only predictive factor for a treatment outcome. ICSI12 was the most predictive cutoff