Aim: To prospectively detect clinically significant bladder outlet obstruction (BOO) in all symptomatic patients presenting with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) by studying select parameters like prostate volume, bladder wall thickness (BWT), intravesical prostatic protrusion (IPP), post-void residue (PVR), and uroflowmetry. Our aim is also to determine the effectiveness of using IPP in correctly predicting BOO in symptomatic patients with BPH, and to compare IPP with other parameters of BOO like prostate volume, bladder wall thickness, PVR, and uroflowmetry in patients with symptomatic BPH.
Methods: After obtaining institutional ethical clearance for this study and administering an informed consent, history, focused urological examination, and International Prostate Symptom Score (IPSS), select ultrasonographic and uroflowmetry parameters were recorded and analyzed in 48 selected patients, as per our protocol.
Results: The mean BWT, PVR, and IPP were 6.26 mm, 91.27 cc, and 8.2 mm, respectively, and their mean maximal flow rate (MFR), average flow rate (AVR), voiding duration, acceleration, and hesitancy time in 44/48 evaluable patients (4 patients had AUR) were 13.68 (3 to 49) mL/min, 7.17 (2 to 25) mL/min, 49.12 (15 to 115) secs, 3.82 (0 to 70) secs, and 13.9 (1 to 242) secs, respectively. The paired sample test (2-tailed) analysis demonstrated that the relationship between BWT vs MFR, IPP (mm) vs MFR, PVR vs MFR, and AFR was highly significant (P < 0.001).
Conclusion: With increasing life expectancy, more men are destined to develop bothersome symptoms due to BPH. Bladder wall thickness and post-void residue in conjunction with intravesical prostatic protrusion are good predictors of clinically significant bladder outlet obstruction due to BPH. A search for more reliable, accurate, and non-invasive methods could substitute present methods of evaluating symptomatic BOO due to BPH.
Iqbal Singh, Shankar Kumar
Submitted February 27, 2013 - Accepted for Publication May 10, 2013
KEYWORDS: BPH, bladder outlet obstruction, bladder wall thickness, post-void residue, intravesical prostatic protrusion
CITATION: UroToday Int J. 2013 June;6(3):art 40. http://dx.doi.org/10.3834/uij.1944-5784.2013.06.14
Benign prostatic hyperplasia (BPH) belongs to one of the most common groups of benign disease of the prostate in aging men. Prevalence of histological BPH increases with age, rising from approximately 40% in men aged 51 to 60 years to 90% by 81 to 90 years. BPH is characterized by obstructive and or irritative symptoms of lower urinary tract obstruction (LUTS) and varying degrees of bladder outlet obstruction (BOO). An evaluation of LUTS due to BPH has been conventionally done by most urologists via a clinical appraisal of LUTS, DRE, and a transabdominal ultrasonographic evaluation. An assessment of clinically significant BOO has been done using different parameters. Clinically significant BOO is urodynamically characterized by increased detrusor pressure (Pdet) and a decreased urinary flow rate. Invasive urodynamic testing with Pdet is not routinely done in all patients with BPH. Non-invasive methods to diagnose BOO include symptom evaluation (an IPSS), prostate specific antigen (PSA), ultrasound derived parameters like prostate-volume, bladder wall thickness (BWT), IPP, and PVR. Of these, ultrasound estimation of the prostate size and PVR with UFM have been routinely used by most urologists the world over to determine the presence of BOO. However, there are very few published studies, and to the best of our knowledge there is no published Indian study describing the accuracy and reliability of using IPP as an index to predict BOO in patients of LUTS due to BPH. This forms the background and rationale for the current study.
MATERIALS & METHODS
Institutional ethical clearance and approval of the research study protocol was obtained prior to this study. The study design was a prospective clinical research study that was conducted in 48 eligible patients in the University College of Medical Sciences, & GTBH, Delhi, visiting the outpatient department of the institution. The protocol, concept, design, and intellectual content for the current study was drafted, conceived, and contributed by the first author who was blinded to relevant patient data at the time of its interpretation and statistical analysis. The patient data as per protocol was recorded by the second author.
As per our protocol, our entry criteria included all symptomatic patients of LUTS due to clinically diagnosed BPH. The exclusion (exit) criteria included patients with BOO due to causes other than BPH; patients with prior urological surgery like transurethral resection of the prostate (TURP), open prostatectomy, diagnosed adenocarcinoma of prostate; patients of BPH with neurogenic bladder, urethral stricture, or vesical stones; and patients previously on medication (alpha blockers, 5-alpha reductase inhibitors, anticholinergics, etc.,) that may affect urine storage/voiding functions.
After ethics administered informed consent, patients were selected as per entry criteria. Medical and or other diagnostic procedures normally associated with the clinical evaluation and diagnosis of such patients of BPH were employed in this research study, as usual. Recruited patients were subjected to clinical evaluation of their LUTS using the International Prostate Symptoms Score (IPSS) questionnaire (to evaluate voiding and storage symptoms), a focused urological examination. Urine analysis, serum prostate specific antigen (PSA), and renal function tests were performed, as usual.
Transabdominal ultrasound of the kidney-ureter-bladder (KUB) region was performed on a full bladder (ingestion of 1 liter of water over a 2-hour period to achieve bladder fullness of at least 200 mL to estimate the intravesical prostatic protrusion [IPP] in mm, prostate volume [mL], and bladder wall thickness [mm]). IPP was measured by estimating the distance from the tip of the prostate’s protrusion in the vesical lumen to the bladder neck (mm). IPP measurement was quantified and graded into 3 grades: grade I, < 5 mm IPP; grade II, 5 to 10 mm IPP; and grade III, >10 mm IPP. Prostate volume was determined using the prolate ellipsoid model: ((Transverse diameter x anteroposterior diameter x cephalocaudal length) ÷ 2) x 100. Post-void residue was determined after voiding with trans-abdominal USG using the formula for a solid ellipse. Uroflowmetry was performed after calibration using the uroflowmetery, and the voided volume, maximal flow rate, average flow rate, hesitancy time, and voiding time were recorded. Results were analyzed using descriptive statistics and the paired samples 2-tailed test.
The mean age, IPSS, serum PSA, and prostate volume of these patients were 62 (43 to 83) years, 16.13 (1 to 35), 1.96 (0.2 to 6.5) ng/dl, and 39.37 (17 to 90) cc, respectively. The average BWT, PVR, and IPP of our enrolled 44 patients was 6.26 (3 to 12) mm, 91.27 (5 to 360) cc, and 8.2 (1 to 20) mm, respectively. Their mean maximal flow rate (MFR), average flow rate (AVR), voiding duration, acceleration, and hesitancy time in 44/48 evaluable patients (4 patients had AUR) were 13.68 (3 to 49) mL/min, 7.17 (2 to 25) mL/min, 49.12 (15 to 115) secs, 3.82 (0 to 70) secs, and 13.9 (1 to 242) secs, respectively. The paired sample test (2-tailed) analysis (see Table 1) demonstrated that the relationship between BWT vs MFR (pair 8), IPP (mm) vs MFR (pair 10), PVR vs MFR, and AFR were also highly significant (P < 0.001).
Transabdominal ultrasonographic estimation of the prostate (BWT, IPP, PVR, PV) with evaluation of LUTS combined with uroflowmetry have been used for diagnosing BOO by various authors. This has been briefly reviewed as depicted in Table 2.
Manieri et al. , in their 174 patients with BPH, demonstrated that BWT cut off at 5 mm was best to diagnose BOO. Hakenberg et al,  also detected that the mean BWT was 3.33 mm in healthy men versus 3.67 mm in men with LUTS and BPH. Oelke et al.  demonstrated BOO in 95.5% of men with a BWT (> 2 mm). Kessler et al,  also concluded in a similar study that BWT of > 2.9 mm had a high predictive value for diagnosing BOO. In the present study, we demonstrated a mean cutoff of 7.4 mm BWT as an accurate predictor of BOO with an inverse correlation between the BWT and maximal flow rate.
Chia et al,  attempted to evaluate the effects of varying degrees of IPP on lower urinary tract function in their subset of 125 patients with BOO. By comparing IPP with the results of the pressure-flow study, they found that IPP was a statistically significant predictor of BOO. Kequin et al, , while evaluating 206 patients with BOO, demonstrated that IPP was a useful predictor of BOO based on their comparison of the IPP (significant was >10 mm) results with other variables. Dicuio et al.  used IPP to define BOO by classifying the degree of IPP as mild (< 5 mm), moderate (5 to 10 mm), and severe (> 10 mm), with a similar finding noted by Lieber et al. . According to a study in 114 patients by Lim et al. , the researchers demonstrated that the degree of IPP was a better predictor for BOO than PSA or prostate volume alone. Zhang et al. , while evaluating 89 patients with BPH, also found a close correlation between IPP and BOO. Reis et al. evaluated 42 patients for IPP, found that a cutoff IPP of 5 mm strongly correlated with BOO, with 95% sensitivity. In the current study, we included the same cutoffs for grading IPP, as was used by Reis et al. . According to Yu et al. , an IPP of > 10 mm cutoff value, when used for the diagnosis of BOO, had an accuracy of 92.7%, and in a similar study, Zhonqhua et al.  demonstrated that an IPP cutoff value > 10 mm was a reliable predictor of BOO.
The variation in the IPP cutoff value used for the diagnosis of significant BOO by various authors [5,6,7,8,9,10,11,12,13] may also be dependent on the prevoid bladder volume, as demonstrated by Yuen et al. . It demonstrated that maximum prostatic protrusion occurred at a bladder volume of 100 to 200 mL. Doo et al.  concluded in another study that IPP was a useful parameter to predict symptoms of BOO, especially in patients with acute urinary retention due to BPH. A recent study by Franco et al.  concluded that when both IPP and BWT were done concomitantly, it had a diagnostic accuracy of 87% in detecting BOO amongst symptomatic BPH patients. Lovvik et al.  reviewed various publications, concluding that IPP may be used clinically and in conjunction with urodynamic investigations for diagnosing BOO. In our study, a mean IPP cutoff of 5.7 mm appeared to be suggestive of significant BOO with an inverse correlation between the IPP and the maximal flow rate.
Goyal et al.  demonstrated that in 69 of their patients with BPH that both transrectal power Doppler sonography and conventional TRUS in conjunction with measurement of uroflow, IPP, and PVR could predict BOO with a high degree of specificity and sensitivity.
There were certain limitations in the current study. This was a non-randomized, non-blinded prospective study without any control group. Transrectal ultrasonography was not used to assess the chosen parameters; the present study was conducted at a single institution and included a limited number of patients. The impact of varying prevoid bladder volume on the BWT and IPP was not evaluated; however, we sought to minimize this by ensuring that enrolled patients had a prevoid bladder (PRV) volume of at least 200 mL. All ultrasound studies were done by a single operator, which was not re-evaluated. Pressure flow studies/cystoscopy/impact of medications, if any, on the chosen parameters of BOO were not evaluated in this study due to our protocol limitations (of keeping this study non-invasive in order to avoid UTIs). Based from the viewpoint of physics, it is believed that the resistance of any tubular structure is related to its radius and its length, and so far there is no evidence to suggest whether the protrusion of the prostate into the bladder is an independent factor for obstruction. While median lobes may protrude significantly into the bladder, it is believed that the same may not be circumferentially compressive of the urethra. This may be a limitation of this study. Most men over the age of 50, with moderately severe LUTS, a prostate volume over 30 cc, and a PSA greater than 1.5, appear to have a significant risk of BPH symptomatic progression, a risk of AUR, and a need for surgery. While IPP may be a good predictor of BOO, the fact of whether any one of them is more predictive of the type of patient that will either request or benefit from management of their BOO, and also which one is better to predict whether the patient will benefit more from medical therapy vs surgical intervention remains unanswered.
We believe that IPSS, BWT, PVR, and IPP are good predictors of clinically significant BOO due to BPH. In the current study, we observed an excellent correlation of BWT, PVR, and IPP for detecting BOO. We demonstrated a statistically significant inverse correlation between the degree/grade of intravesical prostatic protrusion and the maximal flow rate. We believe that estimation of intravesical prostatic protrusion in conjunction with PVR and BWT may be used for an evaluation of clinically significant BOO due to BPH. Furthermore, larger randomized, controlled similar studies incorporating pressure flow studies/cystoscopy/impact of medications on BOO are needed to better establish the clinical relevance of using above IPP criteria as a reliable predictor of BOO.