The impact of the bladder wall thickness on the outcome of the medical treatment using alpha-blocker of BPH patients with LUTS

Abstract

Objectives: To evaluate whether the outcome of medical treatment with α 1 receptor blocker in Benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS) is affected by the bladder wall thickness (BWT)

Methods: A total of 125 male BPH patients with LUTS were enrolled. All patients were assessed using The International Prostatic Symptom Score (IPSS), prostate specific antigen (PSA), prostate volume, uroflowmetry, post voiding residual (PVR). BWT was measured by Trans-abdominal ultrasound, and patients were divided into two groups group 1 (patients with BWT <5 mm) and group 2 (patients with BWT ≥5 mm). The patients were reassessed after 2 months of treatment with α 1 receptor blocker (alfuzosin 10 mg). Clinical parameters were analyzed and compared between groups.

Results: There were significant difference between both groups as regard IPSS, voiding symptoms, and storage symptoms (p = 0.005), (p = 0.010) and (p = 0.041) respectively. After medication, there were improvements in the total IPSS, voiding symptoms, storage symptoms, Qmax, PVR and Qol in both groups and these improvements were more effectively in (group 1) than (group 2) with statistically significant differences (p < 0.05).

Conclusion: BWT has positive correlation with the total IPSS, voiding symptoms subscores and storage symptoms subscores. The response to medical treatment is found statistically less in patients with BWT greater than 5 mm.

• α 1 receptor blocker and Bladder
• Benign prostatic hyperplasia
• lower urinary tract symptoms
• the International Prostatic Symptom Score
• wall thickness

Introduction

Benign prostatic hyperplasia (BPH) is a common urological disease affecting more than 50% of elderly male patients. About 28% complain of moderate to severe LUTS [1,2]. BOO was reported up to 60% of the symptomatic and up to 52% of the non-symptomatic patients with BPH [3,4].

It has been documented that animals with obstructed bladders had considerable increase in the bladder wall thickness due to hypertrophy of the smooth muscle cell, fibrocyte hyperplasia, and deposition of collagen in the wall of the bladder, and these findings were documented in BOO in human [5,6]. The bladder wall can be analyzed with ultrasound technology with accuracy; accordingly, measurements of bladder wall thickness (BWT) have been added recently to diagnose BOO in men with BPH [7].

The International Prostatic Symptom Score (IPSS) is used to determine the degree of LUTS in BPH patients [8], additionally measuring BWT by transabdominal ultrasound is a simple, non-invasive technique to evaluate BOO in BPH patients [9].

Whether or not the response of patients with BOO to alpha 1 adrenoceptor blocking agent is affected with the the degree of BWT is still controversial. Similarly, the relation between the degree of BWT and the BOO needs to be proven [10,11].

In the present study, we evaluate the impact of the BWT on the responsiveness of BPH patients with LUTS treated with alpha1-receptor blockers.

Methods

This was a prospective study that was carried out on 125 male patients who presented to our outpatient clinic in the two centers with LUTS. The study was carried out between December 2011 and May 2013. All the included patients had normal serum total PSA value. All of our patients had Prostate volume ≥25 ml, IPSS ≥8 and no previous history obtained by medical or surgical treatment for LUTS. Patients who had urinary tract infection, bladder disease (tumors, stones and neurogenic bladder), urine retention and urethral stricture were excluded. Also patients with abnormal digital rectal examination (DRE) findings of the prostate suspected malignancy were excluded. All patients underwent a full medical history and clinical examination and were assessed using IPSS, Quality of life (Qol), Bladder wall thickness (BWT) by abdominal ultrasound using a convex probe 5–7 MHZ above pubic symphysis, uroflowmertry and post voiding residual (PVR). The bladder volume should be ≥250 ml. The average of three different measurements 1-cm apart in the anterior bladder wall thickness was reported.

Patients were treated using Alpha-blocker (alfuzosin 10 mg once daily) for two months and reassessed again.

The patients were divided into two groups, group 1 (patients with BWT <5 mm) and group 2 (patients with BWT ≥5 mm; Figures 1 and 2). All patients were given informed consent for their participations.

Figure 1. Bladder wall thickness <5 mm.

Figure 2. Bladder wall thickness ≥5 mm.

Statistical analysis was performed using computer program SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL) version 15. Data were presented in terms of mean ± standard deviation (SD), or frequencies (number of cases) and percentages. Comparison between the two groups was performed by using Student’s t-test. p values <0.05 was considered statistically significant.

Results

We started our study on 125 male patients with lower urinary tract symptoms. About 110 patients who fulfilled the selected criteria continued the study and only 15 patients missed the follow-up.

The mean age of group 1(n = 59) and group 2 (n = 51) patients were 63 ± 7.2 and 66 ± 6.8 respectively (Table 1).

Table 1. Patients’ parameters at baseline.

Parameter	Group 1 (BWT <5 mm) n (59)	Group 2 (BWT ≥5 mm) n (51)	p Value
Age	63 ± 7.2	66 ± 6.8	0.136
Prostate volume	33.1 ± 6.1	35.4 ± 6.3	0.265
PSA	1.45 ± 0.91	1.82 ± 1.3	0.116
IPSS	18.9 ± 3.2	21 ± 4.1	0.005
Voiding score	12.1 ± 3.9	15.6 ± 3.7	0.01
Storage score	8.1 ± 3.2	6.5 ± 3.5	0.041
Postvoid residual	49.1 ± 41.9	62.4 ± 50.3	0.198
Qmax	9.8 ± 3.7	8.6 ± 2.6	0.325
QoL	4.1 ± 0.7	4.5 ± 0.9	0.311

After two months of alfuzosin medication we analyzed the parameters’ data and observed that, there were improvements in the total IPSS, voiding symptoms subscores, storage symptoms subscores, Qmax, PVR and Qol in both groups and these improvement were more pronounced in (group 1) than (group 2) With a statistically significant differences between the two groups p < 0.05 (Table 2).

Table 2. Patients’parameters after 2 months of treatment.

Parameter improvement (%)	Group 1 (BWT <5 mm) n (59)	Group 2 (BWT ≥5 mm) n (51)	p Value
IPSS	52.4 ± 19.8	29.8 ± 12.1	0.0001
Voiding score	55.4 ± 20.4	30.1 ± 13.9	0.0001
Storage score	44.7 ± 29.0	22.1 ± 20.3	0.002
Postvoid residual	46.5 ± 34.2	13.1 ± 75.0	0.01
Qmax	69.1 ± 50.9	31.3 ± 32.8	0.0001
QoL	45.5 ± 18.9	25.1 ± 19.1	0.001

The prostatic volumes of (group 1) and (group 2) were 33.1 + 6.1 and 35.4 ± 6.3, respectively (p = 0.265). According to the PSA, There is no statistically significant difference between the two groups (p = 0.116; Table 3).

Table 3. Patients’ parameters (Prostatic volume – PSA) after 2 months of treatment.

Parameter improvement	Group 1 (BWT <5 mm) n (59)	Group 2 (BWT ≥5 mm) n (51)	p Value
Prostatic volume	31.9 ± 7.4	34.2 ± 6.7	0.196
PSA	1.40 ± 0.81	1.67 ± 1.7	0.211

According to the total IPSS, voiding symptoms subscores and storage symptoms subscores, there were statistically significant differences between the two groups (p = 0.005), (p = 0.010) and (p = 0.041) respectively. However, the post voiding residual, Qol and Qmax were not statistically significant difference between the two groups at the baseline

According to the prostatic volume and PSA, there were improvement noticed in group 1 and group 2 after treatment but these improvement showed no significant differences between the two groups (p = 0.196; p = 0.211; Table 3).

Discussion

Several studies reported a positive correlation between the bladder wall thickness and the bladder outlet obstruction (BOO). Several experimental studies have observed similar findings in animals with BOO [12,13]. This might be attributed to bladder smooth muscle cell hypertrophy and hyperplasia. Histological examination has revealed bladder smooth muscle cell hypertrophy and hyperplasia, the hypertrophy of the smooth muscle cell shows extensively separated muscle cells with decrease of intermediate cell junctions and collagen deposition between muscle cells spaces [12,14].

As a result of this myohypertrophy, the detrusor muscle becomes weaker resulting in more pronounced lower urinary tract [13,19]. These findings agree with our results regarding to the total IPSS, voiding symptoms subscores and storage symptoms subscores, there were statistically significant differences between the group1 and group 2 patients p = 0.005, p = 0.010 and p = 0.041, respectively.

It is well established that the bladder wall thickness is affected by several factors including, sex, age, bladder filling and some pathological states, such as BOO caused by LUTS. BWT increase with age is seen in males and females and this increase was obvious in males [15]. By using ultrasonic measurement methods, the BWT is decreased by 0.00108 mm, for every milliliter added to the bladder volume [16]. Consequently, a 50 mL added to the bladder volume decreases the BWT by about 0.054 mm, and eventually BWT measurements were not considered in patients with a bladder volume extensively less than 250 mL. Oelke et al. established that BWT decreased speedily throughout the first 250 ml of bladder filling but after that reached a plateau phase [17].

In the current study, we used bladder volume ≥250 ml to assess the patients’ BWT, measured by transabdominal ultrasonography (available, practical, low cost, easy, rapid and non-invasive technique) in the diagnosis and follow-up of patients with BPH.

The bladder wall consists of bladder adventitia, which appears hyperechoic on US, followed by bladder muscle layer, which appears hypoechoic on US. The internal layer is the bladder mucosa, which appears hyper echoic on US. BWT is measured by involving the inner and outer hyperechoic outline [17,18].

Manieri et al. was the first to use 5 mm as a cutoff point for BWT. In their study, they documented that 87.5% of male patients with a BWT >5 mm had BOO whereas 63.3% of those with BWT <5 mm were non-obstructed [7]. Based on their finding, we divided our patients into 2 groups group 1(patients with BWT <5 mm) and group 2 (patients with BWT ≥5 mm) and significant correlations between BWT and total IPSS at the beginning with a cut-off point of BWT 5 mm were observed (p = 0.005).

On the other hand, Kessler et al. in their study disagreed with Manieri et al. regarding the best cutoff point for BWT. They stated that BWT ≥2.9 mm is considered the best cut-off point with a elevated predictive value for the diagnosis BOO [19], lately Oelke et al, considered a cut-off of 2 mm to diagnose BOO with a 89% accuracy [20]. Also, Yilmaz and colleagues reported no association between BWT and IPSS [21].

In our study, there were no statistical significant differences in the patients’ age, prostate volume, PSA, PVR, Qmax and QoL between the two groups at the baseline. These results were in agreement to results obtained by Park et al. [22].

According to the IPSS, there was statistical significant difference in pre-treatment total IPSS (p = 0.005). Also there were statistically significant differences between both groups as regard the voiding sub score and storage sub score (p = 0.010) and (p = 0.010), respectively.

Furthermore, after two months of α-blocker (alfuzosin), the percentage improvement was increased in (group 1) than in the (group2). In (group 1), all parameters (except PSA and prostatic volume) were significantly improved at the end of the study compared with (group 2).

According to our results, BWT was not significantly related to prostate volume and PSA, which is matched with the findings of Park et al. [22].

Our results advocate that physician should consider BWT in the treatment BOO associated with LUTS. Further randomized, placebo-controlled and urodynamic studies with longer follow-up durations may be required to verify our findings.

We concluded that increased BWT has positive correlation with the total IPSS, voiding symptoms subscores and storage symptoms subscores. Moreover the increase in BWT is associated with a poorer response to alpha-blockers. BWT should be considered a useful method for predicting the outcomes of alpha-blocker treatment in LUTS/BPH patients

Declaration of interest

There are no conflicts of interest.