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Keywords:

  • LUTS;
  • blood perfusion;
  • ischaemia;
  • elderly;
  • ultrasonography;
  • resistive index

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

OBJECTIVES

To investigate, using transrectal colour Doppler ultrasonography, (TRCDUS) whether perfusion of the bladder and prostate is reduced in elderly patients with lower urinary tract symptoms (LUTS), common in later life, as experimental data suggest that chronic ischaemia has a key role in the development of LUTS.

PATIENTS, SUBJECTS AND METHODS

In 32 elderly patients with LUTS (12 women, mean age 82.3 years, group 1; and 20 men, 79.4 years, group 2) perfusion of the bladder neck (in women) and of the bladder neck and prostate (in men) was measured using TRCDUS and the resistive index (RI) and colour pixel density (CPD) determined, assessed by a TRUS unit and special software. To assess the age-related effect two control groups of 10 young healthy women (mean age 42.3 years, group 3) and 10 age-matched healthy men (mean age 41.5 years, group 4) were also enrolled.

RESULTS

Irrespective of gender, there was markedly lower bladder perfusion in elderly patients with LUTS than in the younger subjects. The mean (sd) RI of the bladder neck in group 1, of 0.88 (0.06), and group 2, of 0.80 (0.08), was higher than in control groups 3, of 0.62 (0.05), and group 4, of 0.64 (0.09). The results were similar for the CPD measurements. The frequency of daily and nightly micturition showed a strong negative correlation with perfusion in the urinary bladder.

CONCLUSION

In elderly patients with LUTS there was decreased perfusion of the bladder neck and prostate when assessed using TRCDUS. Therefore, decreased perfusion in the urinary bladder might be responsible for the development of LUTS with advancing age.


Abbreviations
(TR)(CD)US

(transrectal) (colour Doppler) ultrasonography

RI

resistive index

CPD

colour pixel density

QoL

quality-of-life (score)

TZ, PZ

transition and peripheral zone.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

LUTS are common in later life and can have a major influence on the quality of life of elderly people. However, the aetiology of LUTS is still poorly understood. In the male, LUTS are commonly associated to BOO due to an enlarged prostate, but in previous studies, in a third to more than a half of men LUTS was not associated with BOO [1,2]. Elderly women, who are much less prone to develop BOO, can also have similar LUTS. These observations suggest that the pathophysiological basis of LUTS in the elderly might involve gender-independent, age-associated changes affecting the smooth muscle, urothelium, vasculature and/or innervation of the urinary bladder. Atherosclerosis, also a common disease of ageing, has been implicated in pelvic organ dysfunction.

Experimentally, bladder ischaemia has been shown to produce significant changes in bladder function and structure, leading to noncompliance and hyper-reflexia [3–5]. Ischaemia-induced cellular and molecular changes in the bladder are similar to those induced by overdistension and partial BOO [4]. It was suggested that the chronic bladder ischaemia caused by atherosclerosis might be a cause of voiding dysfunction in the ageing bladder [2].

The accuracy and feasibility of ultrasonographic (US) measurements of blood flow in the urinary bladder neck was assessed recently in a pig model during comparative cystometry. It was shown clearly that transrectal colour Doppler US (TRCDUS) could be used to obtain comparable results to laser Doppler flowmetry perfusion measurements [6]. Therefore, we used TRCDUS to investigate whether perfusion of bladder and prostate is reduced in elderly men and women with LUTS.

PATIENTS, SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

In all, 32 elderly patients with LUTS (12 women, mean age 82.5 years, group 1; and 20 men, 80.4 years, group 2) had perfusion of the bladder neck (in women) and bladder neck and prostate (in men) measured using TRCDUS; the resistive index (RI) and colour pixel density (CPD) were also assessed. For all measurements, we used a TRUS unit (Sequoia 512, Acuson, Mountain View, CA, USA), with the high-frequency end-fire probe EC10C5, and special software (Scion Image Analysis Software, Frederick, Maryland, USA). To assess the age-related effect, two control groups comprising 10 healthy women (group 3) and 10 healthy men (group 4) were enrolled.

On initial examination a complete medical history was obtained by a standardized interview. LUTS were evaluated using the IPSS [7] and quality-of-life (QoL) score. The question about the patient’s QoL with LUTS was ranked on a scale of 0 (‘delighted’) to 6 (‘terrible’). Patients with pelvic cancer, a history of previous surgery or pelvic inflammation were excluded from the study. A negative urinary analysis was mandatory for study enrolment.

During imaging, with the patients placed in the decubitus position, care was taken to minimize probe pressure. All participants were examined with an empty or nearly empty bladder, to preclude compression of the intraprostatic and bladder neck vessels. Contrast-enhanced TRCDUS was used to visualize the arteries of the bladder, bladder neck and prostate (transition and peripheral zone, TZ and PZ) to measure the RI (Fig. 1). The Doppler signal intensity in all zones was determined using computer-assisted quantification of CPD. The region of interest was placed in areas with the highest detectable blood flow. For this purpose the red-green-blue output of the TRUS unit was digitized using a computer. The digitized images were post-processed with the National Institute of Health image software package (version 1.62). In each subject, computer-assisted quantification of CPD was used in areas of the outer and the inner gland.

image

Figure 1. Original CDUS blood perfusion measurements and assessment of blood flow velocities as a variable of perfusion of the LUT. a, Transvaginal, sagittal US in an elderly women with LUTS (group 1); b, TRCDUS blood perfusion measurement in the prostate (left image, coronal view) and bladder neck (right image, sagittal view) in an elderly man (prostate volume 27 mL) from group 2; c, Transvaginal US of the bladder neck in one healthy woman (group 3); d, TRCDUS blood perfusion measurement of the prostate in one asymptomatic young man (group 4).

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Differences among the four groups were analysed with the Kruskal–Wallis test; if it indicated statistical significance, post hoc tests were done using Student’s t-test, using a two-sided significance level of 0.05 for all analyses.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

In all 52 subjects the CDUS studies were conducted successfully. The characteristics of the study population are shown in Table 1. The IPSS and QoL scores in patients with LUTS were significantly worse than in the controls. Irrespective of gender, the bladder perfusion was markedly lower in elderly patients with LUTS than in the younger subjects. The mean (sd) RI of the bladder neck in group 1 and 2, as measured by CDUS, was lower than in control groups 3 and 4 (Fig. 2; Table 1). The findings were similar for the CPD measurements. Perfusion of the TZ of the prostate was significantly lower in patients with LUTS (median 178.5) than in healthy controls (median 276). For perfusion of the PZ there was no statistically significant difference between the groups (P = 0.291). Patients with LUTS had larger prostates (median 47.8 mL) than the healthy controls (33.5 mL). The frequency of daily and nightly micturition showed a strong negative correlation with perfusion in the urinary bladder. Elderly patients with LUTS had a significantly higher IPSS and worse QoL, together with decreased blood perfusion, as expressed by a higher RI in the LUT.

Table 1.  The characteristics of the four groups of subjects
VariableGroup
1234
GenderFMFM
Number20201010
Mean (sd) age, years82.3 (3.2)79.4 (3.7)42.3 (7.8)41.5 (5.5)
Prostate volume, mL47.833.5
Body mass index, kg/m226.528.125.325.3
IPSS17.818.2 3.8 3.4
QoL score 4.6 4.5 2.1 1.9
Maximum flow rate, mL/s17.312.527.524.3
Mean (sd) RI 0.88 (0.06) 0.80 (0.08) 0.62 (0.05) 0.64 (0.09)
image

Figure 2. A box-and-whisker diagram of the blood perfusion expressed as the mean RI between elderly patients and asymptomatic younger controls. The boundaries of the box are Tukey’s hinges, the length of the box is the interquartile range computed from Tukey’s hinges. Upper and lower whiskers represents the highest and lowest values, respectively. There was lower perfusion in the LUT as assessed by TRCDUS blood perfusion measurements, with significantly higher RI values in elderly patients with LUTS than in younger subjects (** P < 0.001 for women and men).

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Ageing is associated with declining function in nearly every physiological system [8–10]. LUTS are more prevalent among the elderly [3,11] and clinical urodynamic studies show advancing age to be associated with a reduced bladder capacity, an increase in uninhibited contractions, decreased urinary flow rate, diminished urethral pressure profile (particularly in women), and increased postvoid residual urine volume [12–15]. The ageing bladder specifically can be described as manifesting detrusor overactivity, impaired contractility, or a combination of both [16,17].

Several epidemiological and cross-sectional studies have shown decreased QoL with increasing LUTS in elderly patients [18–20]; in the present study LUTS apparently had an independent effect on QoL beyond the effect of potentially more serious comorbidities [21]. Although LUTS are not life-threatening their effect on daily living is as influential as some more obvious and potentially life-threatening concomitant diseases.

However, the causes of bladder dysfunction, urinary incontinence and LUTS are poorly understood. In men LUTS are commonly attributed to BOO caused by an enlarged prostate. However, in about a third to more than a half of men, LUTS are not associated with BOO [1,2]. In one recent study 28 men (mean age 66.4 years) with so-called BPH were assessed for LUTS by urodynamic investigations, that showed altered detrusor function in 75% and reduced bladder sensation in further five of the patients (17%). The observed detrusor overactivity did not correlate with prostate size or urodynamically defined BOO [22]. Similarly, Jacobsen et al.[23] investigated 464 men aged 40–80 years, using TRUS measurements of prostatic volume, an assessment of urinary flow rates and the AUA symptom score. They reported only a very weak relationship of prostate size with the symptom score. In the present study there was also no significant correlation between LUTS severity and prostate volume.

Interestingly, when women are asked to complete symptom questionnaires designed to document LUTS, they yield identical scores to their age-matched male counterparts [8,9]. Similarly, urodynamic studies show that there are age-specific changes in bladder function affecting both genders [8,9,24]. The incidence of age-associated urodynamic changes, including decreased maximum flow rate, voided volume and bladder capacity and an increase in postvoid residual volume, are similar in both sexes [10]. These observations suggest that the pathophysiological basis of LUTS in the elderly might involve gender-independent, age-associated changes affecting the smooth muscle, urothelium, vasculature and/or innervation of the urinary bladder.

The relationship between ageing and increased prevalence of bladder dysfunction, urinary incontinence and LUTS has been reported often [1,2,8]. Detrusor overactivity, the most common cause of age-associated urinary incontinence, is present in 40–70% of the elderly population [9,10]. Moreover, the prevalence of urinary incontinence increases from 30% in institutionalized elderly patients aged ≥60 years, to 84% in nursing-home residents aged ≥85 years [1,2,8]. Although ageing and detrusor overactivity are apparently closely associated, the mechanisms by which ageing leads to functional changes in the bladder have not been well understood.

Vascular disease is common in the elderly, leading some to speculate that bladder ischaemia might have a role in the pathophysiology of LUTS [3]. Vascular occlusive disease and concomitant chronic ischaemia have been reported to produce smooth muscle dysfunction in several organs, including the intestine [11], stomach [12], prostate [25] and penile erectile tissue [13,14]. This association appears to be true also for the bladder. A close relationship between a history of cardiovascular disease and the prevalence of urinary incontinence was reported [15]. Vascular risk factors such as smoking and hypertension have also been associated with LUTS [16,26]. Experimentally, bladder ischaemia has been shown to produce significant changes in bladder function and structure, leading to non-compliance and hyper-reflexia [3–5,27] Ischaemia-induced cellular and molecular changes in the bladder are similar to those induced by overdistension and partial BOO [4]. Clinical studies suggest that ischaemia might have a partial role in the development of interstitial cystitis and painful bladder syndrome [28,29].

Various studies all show that bladder dysfunction can be caused by ischaemia and suggest that atherosclerosis might be associated with ageing bladder dysfunction. Fewer studies have focused on understanding the pathophysiological mechanisms underlying symptoms in the ageing bladder. This might be because of the need for invasive procedures, e.g. catheterization, for urodynamic studies. Even when studies are conducted, it is often difficult to differentiate between dysfunction due to disease (such as prostatic enlargement) and changes that are purely age-related. In addition, medications taken by many older patients can further confuse the interpretation of clinical studies in this field.

In a previous study, Berger et al.[30] reported a significantly lower CPD and higher RI in the TZ of patients with vascular disease than in healthy subjects. This supports the hypothesis that an age-related impairment of blood supply to the prostate has a key role in the development of BPH. In a recent study by Mitterberger et al.[31] persistent detrusor overactivity in men after TURP seemed to be associated with increased vascular resistance of the bladder vessels, with subsequent reduced perfusion and hypoxia. Both studies used CDUS for to evaluate perfusion.

In the present study, irrespective of gender, there was markedly lower bladder perfusion in elderly patients with LUTS than in younger subjects. The present data also confirm early findings in this field and emphasizes the role of ischaemia in the development of LUTS in elderly patients. Possible limitations of the study design were the relatively few patients included, and that no interobserver variability was evaluated, as all examinations were conducted by one experienced uro-radiologist. However, the assessment of RI and CPD reduces the observer variability and are objective measures for evaluating blood flow. Furthermore, as the study objective was to assess the perfusion of the bladder and/or prostate, we investigated elderly patients with LUTS and compared the findings with those from healthy young controls. This might introduce a bias, as the perfusion might change with increasing age. Nevertheless, in a preliminary pilot study comparing elderly patients with and without LUTS (each group comprising seven patients) we found no significant difference in the blood perfusion in the bladder neck, as observed in the present study. Therefore, an accurate study that compares elderly with and without LUTS is desirable, to evaluate the exact effect of age on bladder and/or prostate ischaemia.

In conclusion, the present study showed that in elderly patients with LUTS, chronic ischaemia of the urinary bladder could be detected as lower perfusion found on TRCDUS, which could not be detected in both asymptomatic groups of younger controls. Therefore, decreased perfusion in the urinary bladder and/or prostate might be responsible for the development of LUTS, which is more common with advancing age. These results suggest the need for further pharmacological investigations into the relationship between the development of LUTS and vascular perfusion of the LUT.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES