MP89-17 DIFFERENT INJECTION NUMBER OF INTRAVESICAL ONABOTULINUMTOXINA INJECTION FOR OVERACTIVE BLADDER SYNDROME DOES NOT AFFECT TREATMENT OUTCOME - A PROSPECTIVE RANDOMIZED COMPARATIVE STUDY

THE JOURNAL OF UROLOGYâ

e1106

(LF/HF) values as an indicator for sympathetic activity. We then retrospectively investigated the associations of these parameters regarding ANS activity; HF, LF/HF and heart rate (HR) with urinary frequency recorded in the activity logs during the 24-hour Holter ECG using Spearman’s correlation coefficient and Wilcoxon rank-sum test. RESULTS: The average numbers of urinations in all cases were 6.09
2.06 times during the daytime and 0.87
1.16 times during the nighttime. Spearman’s correlation coefficient analysis showed a significant inverse correlation between age and each of HF, LF/HF and HR. A significant correlation was found between the number of daytime urinations and HR, and between the number of nighttime urinations and LF/HF. In men, a significant correlation was noted between the number of nighttime urinations and HR, whereas in women, a significant correlation existed between the number of daytime urinations and HR, between the number of nighttime urinations and HF, and between the number of nighttime urinations and LF/HF. CONCLUSIONS: Although the present study is a retrospective review of ambulatory patients who underwent 24-hour Holter ECG, its findings suggest that there are associations between ANS activity and urinary frequency, and different outcomes were observed depending on the age and gender. However, some of the participants had such underlying diseases as hypertension and diabetes, and particularly in elderly patients, ANS activity tend to decrease relatively due to the impact of arteriosclerosis and other such conditions. Therefore, these factors must be taken into account when interpreting the findings. HR has the potential to serve as an easily measurable urinary parameter. Thus, we intend to investigate this potential in a prospective study targeting patients with LUTS.

Vol. 193, No. 4S, Supplement, Tuesday, May 19, 2015

Table 1 Parameters before and after after treatment OABSS

USS

PPBC

DIFFERENT INJECTION NUMBER OF INTRAVESICAL ONABOTULINUMTOXINA INJECTION FOR OVERACTIVE BLADDER SYNDROME DOES NOT AFFECT TREATMENT OUTCOME - A PROSPECTIVE RANDOMIZED COMPARATIVE STUDY

UUI/3D

Urgency/3D

Frequency/3D

FBC (mL)

Chun-Hou Liao*, New Taipei City, Taiwan; Jing-Hui Tian, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: The high rates of treatment-related adverse events (AEs) prevent widespread use of intravesical onabotulinumtoxin A (BoNT-A) injection for refractory detrusor overactivity (DO) or overactive bladder (OAB). Adjusting the injection number is one possible way to minimize the de novo AEs and maintain the therapeutic effects. This prospective randomized comparative trial compared the therapeutic effects and safety of intravesical BoNT-A injection with different injection number. METHODS: Patients with urodynamic DO, at least one episode of urgency or urgency incontinence per day, and refractory to previous antimuscarinics, were randomly assigned to receive intravesical injection of BoNT-A 100 U with 10, 20, and 40 injections at bladder body. Treatment results were assessed by global response assessment (GRA), overactive bladder symptom score (OAB-SS), Urgency severity score (USS), Patient Perception of Bladder Condition (PPBC), voiding diary, and urodynamic parameters. RESULTS: Sixty-seven patients (34 male and 33 female, mean age 65 years) were randomized into 3 groups. Patients with GRA1 were comparable among 3 groups at 1 month, 3 months, and 6 months after treatment. The average number of OAB-SS, USS, and PPBC decreased while the average post-void residual urine (PVR) increased in all 3 groups. The changes of urodynamic parameters and parameters in void diary were also comparable among groups. There was no significant difference in the rates of adverse events and urinary tract infection. CONCLUSIONS: Intravesical BoNT-A injections with different injection number had similar therapeutic and adverse effects. We therefore proposed injection at 10 sites with 1 mL BoNT-A solution (containing 10 U) is adequate for an optimal therapeutic effect on OAB.

20 sites (n¼22)

40 sites (n¼21)

11.67
2.77

11.82
2.63

11.81
1.99

#P value

1 M

9.55
3.17*

8.95
3.05*

9.15
3.54*

0.946

3 M

8.57
3.76*

9.48
3.53*

8.89
3.12*

0.700

6 M

8.56
3.50*

8.53
2.95*

7.14
3.55*

0.630

B

3.71
0.69

3.73
0.63

3.95
0.22

1 M

3.45
0.96*

3.05
0.89*

2.90
1.17*

0.059

3 M

3.05
1.20*

3.29
1.10

3.39
1.20

0.712

6 M

1.89
0.96*

3.16
0.96*

2.71
1.44*

0.183

B

4.79
1.64

4.64
1.71

4.24
1.70

1 M

2.64
1.05*

3.00
1.78*

2.15
1.23*

0.522

3 M

4.90
1.64*

3.19
1.72*

2.71
1.49*

0.414

6 M

2.50
1.25*

2.84
1.61*

2.71
1.86*

0.325

B

9.86
13.11

5.29
7.64

8.95
10.74

1 M

5.00
9.70*

4.00
7.68

5.16
8.98*

0.191

3 M

6.70
12.58*

7.58
18.93

6.70
12.58*

0.237

6 M

5.33
12.17*

5.44
16.66

1.71
2.34*

0.442

Parameters in 3-day Void Diary

Source of Funding: None

MP89-17

10 sites (n¼24) B

B

29.38
18.18

27.10
12.20

31.71
16.82

1 M

18.84
17.21*

28.05
29.10

22.42
21.00*

0.163

3 M

23.40
15.76

27.74
25.04

23.40
15.76

0.493

6 M

20.00
16.19

24.94
32.40*

17.36
16.33*

0.476

B

38.95
15.99

37.00
10.70

40.29
18.29

1 M

34.29
9.57*

37.15
24.77

35.68
13.46

0.617

3 M

34.00
9.57

36.37
20.27

39.06
23.93

0.452

6 M

33.60
11.00*

34.22
28.35*

31.93
14.37

0.723

B

305.57
116.40

280.71
101.39

360.95
170.29

1 M

322.86
143.46

286.00
85.86

318.42
192.85

0.315

3 M

311.25
126.20

288.95
115.71

307.50
157.47

0.227

6 M

320.33
130.36

297.22
94.67

367.14
163.40

0.801

Urodynamic parameters CBC (mL)

Qmax (mL/s)

Volume (mL)

PVR (mL)

B

220.38
108.23

249.68
120.64

266.14
193.88

3 M

337.41
135.05*

337.13
157.78

362.47
229.26*

0.523

6 M

425.75
279.46

323.38
141.13*

286.86
70.12

0.103

B

14.63
10.55

14.45
9.81

17.05
12.96

1 M

14.35
8.89

12.95
7.51

13.11
11.44

0.933

3 M

13.33
9.29

15.71
8.75

17.18
16.20

0.833 0.825

6 M

15.33
7.70

13.89
10.58

18.43
15.82

B

186.21
106.14

188.95
97.04

232.14
151.50

1 M

217.00
136.72

190.57
85.93

185.47
96.66

0.310

3 M

215.71
134.20

214.38
91.33

241.12
189.75

0.447

6 M

217.50
130.89

194.74
113.57

239.50
114.13

0.174

B

26.46
28.01

67.59
65.22

56.33
149.59

1 M

134.30
99.11*

169.76
92.43*

131.47
99.06*

0.569

3 M

93.95
84.16*

178.90
105.63*

121.82
134.49*

0.771

6 M

73.17
67.29*

105.00
82.58

84.29
82.80

0.608

* p < 0.05 comparing parameters at baseline and after treatment using Wilcoxon sign rank test; #: comparisons of the changes before and after treatment among groups using ANOVA test; B: basline; FBC: functional bladder capacity, OAB-SS: overactive bladder symptom score; PPBC: patient perception of bladder condition; PVR: postvoid residual; Qmax: maximal flow rate; USS: urgency severity score; UUI: urgent urinary incontinence

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e1107

Table 2 PGII Responses in DU and BOO Populations

Table 2 Common AEs after intravesical BoNT-A 10 sites (n ¼ 24)

20 sites (n ¼ 22)

40 sites (n ¼ 21)

P value

1

2

3

4

5

6

7

DU (n¼85)

18

32

16

11

6

2

0

Hematuria

4 (16.7%)

5 (22.7%)

3 (14.3%)

0.756

BOO (n¼37)

18

7

2

5

4

1

0

Urinary retention

3 (12.5%)

1 (4.5%)

2 (9.5%)

0.637

Bladder pain

0

1 (4.5%)

2 (9.5%)

0.305

1 (4.2%)

1 (4.5%)

0

0.623

Large PVR (200 mL)

10 (41.7%)

13 (59.1%)

8 (38.1%)

0.329

Dysuria

8 (33.3%)

6 (27.3%)

5 (23.8%)

0.771

UTI

3 (12.5%)

7 (31.8%)

2 (9.5%)

0.079

Micturition pain

UTI: urinary tract infection; *Comparisons among groups using Fisheris exact test

PGII Score

Source of Funding: Institute for Bladder and Prostate Research

MP89-19 INCREASE OF SUBMUCOSAL INFLAMMATION AND DECREASE OF UROTHELIAL BARRIER FUNCTION ARE FOUND IN PATIENTS WITH DETRUSOR UNDERACTIVITY - AN IMMUNOHISTOCHEMISTRY STUDY Shiu-Dong Chung*, New Taipei City, Taiwan; Jia-Hui Chang, Hann-Chorng Kuo, Hualien, Taiwan

Source of Funding: none

MP89-18 TURP/KTPLAP: AN EFFECTIVE TREATMENT FOR MEN WITH DETRUSOR UNDERACTIVITY (DU) & BLADDER OUTLET OBSTRUCTION (BOO) Michael Tyler*, Matthew Benedon, Joshua Aizen, Anand Badri, Jeffrey Weiss, Jerry Blaivas, New York, NY INTRODUCTION AND OBJECTIVES: In this study, we report outcomes of men with detrusor underactivity (DU) & bladder outlet obstruction (BOO) treated with KTP laser ablation (KTPLAP) or transurethral resection of the prostate (TURP). METHODS: This is a retrospective study of consecutive patients with DU (defined by a bladder contractility index (BCI) < 100) who underwent KTPLAP or TURP because of presumed BOO (PBOO). Presumed BOO was diagnosed when the product of detrusor contraction time and a Qavg of 12 mL/S was  bladder capacity. The rationale for this is that if the bladder contracted long enough to empty at a normal flow, reducing outlet resistance by surgery would improve voiding dynamics; ie, there is a relative BOO. Men with DU & PBOO were compared with a matched cohort of those with BOO only. A subset analysis was also performed of patients with DU due to an acontractile bladder comparing those with and without the ability to void during clean intermittent catheterization (CIC) regimen. Pre and post-operative urodynamic parameters were measured along with need for CIC. The primary outcome measure was the Patient Global Impression of Improvement (PG-II). Success was defined as a PG-II score of 1-3. Comparisons were made using a two-sided t-test. RESULTS: The results of outlet reducing surgery are equal with respect to both subjective and objective outcomes in men with DU & PBOO and BOO. However, only 1/8 patients with an acontractile detrusor had a successful outcome, independent of whether they were able to void spontaneously while on preoperative CIC. See tables 1 and 2 for complete comparison of data. CONCLUSIONS: TURP or KTPLAP area equally effective in men with BOO and those with detrusor underactivity and presumed BOO. However, an acontractile detrusor is a poor prognostic sign.

INTRODUCTION AND OBJECTIVES: Patients with underactive bladder (UAB) or detrusor underactivity (DU) usually have a diminished bladder fullness or urgency sensation and cannot contract the detrusor sufficiently to complete bladder emptying. It is possible that the bladder urothelial dysfunction, sensory nerve dysfunction, detrusor myogenic dysfunction, as well as the impaired central nervous system control are involved, in part or totally, in the development of UAB/DU. METHODS: We have investigated the urothelial dysfunction in 35 patients with DU and 20 normal controls. The DU patients included 24 with detrusor areflexia (DA, 15 women and 9 men, mean age 52.42
18.37 years) and 11 with detrusor overactivity and impaired contractility (DHIC, 8 women and 3 men, mean age 63.09
21.14 years). Bladder biopsies were harvested from the posterior wall durining transurethral procedure to facilitate spontaneous voiding. The bladder biopsy sections were incubated overnight at 4 C with primary antibodies to antihuman E-cadherin, anti-human zonula occludes-1(ZO-1). Immunofluorescence staining image of E-cadherin and mast cell tryptase were captured using fluorescence microscopy with digital image system. While the distribution and fluorescence intensity of ZO-1 was obtained using a confocal microscope. Expression of E-cadherin and ZO-1 in urothelium will be quantified with the Image J software. Apoptosis of urothelial cells were performed using TUNEL assay. The total cell population were visualized using a 330-380 nm filter for DAPI, while the analysis labeled nuclei were visualized using a standard fluorescein filter (465-495 nm). RESULTS: Junction protein E-cadherin was significantly lower in patients with DU, suburothelial inflammation was significantly higher and the urothelial cell apoptosis was significantly higher in patients with DU. However, the barrier protein ZO-1 showed no significant difference between DU and controls (Table 1) (Fig. 1). There was no significant difference in any parameters between bladders of DA and DHIC. CONCLUSIONS: These results indicate that chronic inflammation and urothelial dysfunction are present in the DU/UAB bladders. The lower expression of E-cadherin may be associated with decrease bladder sensation during mucosal stretching. Table 1 Clinical data and immunohistochemistry results in patients with detrusor underactivity Normal (N¼20)

DU (N¼35)

DA (N¼24)

DHIC (N¼11)

38.4
19.2

21.1
18.6

23.7
20.0

15.4
14.4

3
2.83

10.62
5.63

11.26
6.09

9.22
4.38

TUNEL

0.49
0.99

6.16
3.24

5.98
3.21

6.55
3.44

ZO-1

8.23
4.99

7.91
3.36

7.7
2.65

8.39
4.67

Age (years)

57.9
11.69

55.77
19.62

52.42
18.37

63.1
21.14

Compliance

157.0
139.5

68.3
111.2

81.2
132.1

41.4
35.0

FSF (mL)

178.5
63.0

164.4
88.2

179.9
96.7

132.1
58.4

E-cadherin

Table 1 Characteristics of DU and BOO populations

Mast-cell

DU (n¼85)

BOO (n¼37)

p-value

Age

69
12

67
13

0.44

BCI

51
27

125
24

<0.00001

BOOi

22
26

66
43

<0.00001

Bladder Capacity (ml)

691
528

554
299

0.07

FS (mL)

327.5
80.0

253.3
146.2

281.6
162.5

190.2
82.2

Pre-Op Qmax (ml/s)

4.2
3.6

8.3
6.9

0.001

US (mL)

402.7
102.6

289.0
149.8

314.4
158.9

236.1
117.9

Pre-Op PVR (ml)

458
429

507
434

0.57

CBC (mL)

412.4
108.8

293.0
149.0

317.8
157.1

241.2
120.8

Pdet (cmH2O)

22.59
14.32

7.79
12.38

2.04
3.43

19.8
15.7

n¼42 (49%)

n¼16 (43%)

N/A

Qmax (mL/s)

19.59
11.61

2.26
3.29

1.91
3.54

3
2.68

14.7
9.7

19.4
10.2

0.02

PVR (mL)

44.7
84.4

373.5
201.8

388.7
230.3

341.8
127.0

Pre-Op CIC Post-Op Qmax (ml/s) Post-Op PVR (ml)

111
203

74
62

0.14

Post-Op CIC

n¼16 (19%)

n¼0 (0%)

N/A

PGII success

n¼66 (78%)

n¼27 (70%)

N/A

CBC: cyctometric bladder capacity; DA: detrusor areflexia; DHIC: DO with inadequate contractility; DU: detrusor underactivity; FS: full sensation; FSF: first sensation of filling; Pdet: detrusor pressure; PVR: post-void residual urine; Qmax: maximum flow rate; US: urgency sensation; ZO-1: zonula occludens-1

Source of Funding: none