RELATIONSHIP BETWEEN TZI AND TZV WITH IPSS, QMAX, AND BOO

Objective: This study evaluate the relationship between the IPSS score, Qmax, and degree of bladder outlet obstruction with transitional zone volume (TZV) and transitional zone index (TZI) in clinical BPH patient. Material & Methods: This is an observational cross sectional study which 26 patients included with clinical BPH between September 2011 until January 2012. General information and other variables are recorded (total prostate volume, TZV, TZI, IPSS score, Qmax and degree of bladder outlet obstruction (BOO) according to Schaefer normogram. The data will be descriptive and analytically analyzed. Results: 26 patients with clinical BPH are included in this study, with average age is 64,7 (± 5,98) years. The average volume of the total prostate volume and TZV are 30,35 (± 15,35) gram and 15,31 (± 11,77) gram. Meanwhile the average of TZI is 0,4 (± 0,13). After the normal distribution test was performed, all data is analyzed with Pearson correlation test. A strong correlation was found between IPSS and total prostate volume (r = 0,526, p = 0,006), TZV (r = 0,671, p = 0,000) and TZI (r = 0,812, p = 0,000). A strong correlation is also found between TZI and BOO (r = 0,560, p = 0,003). Meanwhile weak correlation is found between Qmax and total prostate volume (r = -0,105, p = 0,608), TZV (r = 0,103, p = 0,616) and TZI (r = 0,084, p = 0,734). Another weak correlation is shown between total prostate volume (r = 0,233, p = 0,253) and TZV (r = 0,37, p = 0,062) with degree of BOO according to Schaefer nomogram. Conclusion: TZV has significant correlation with IPSS score, but no significant correlation with Qmax and degree of BOO in patients with clinical BPH. Meanwhile TZI has a significant correlation with IPSS and degree of BOO in patients with clinical BPH. TZI could be performed as a single non invasive procedure to determine BOO in patients with clinical BPH.


INTRODUCTION
Prostate volume has been used a parameter in determining diagnosis and therapy in patients with clinical BPH. However, total prostatic volume which is an objective measure for BPH is not always related to these verity of lower urinary tract symptoms 1 (LUTS) or other physiological parameters.
McNeal divided prostate gland in several zones, which are the peripheral, central, transitional, anterior fibromuscular, and periurethral zone. Seventy percent of the total volume of an adult male prostate is peripheral zone, 25% central zone, the other 5% is transitional zone. Most prostatic hyperplasia are found within the transitional zone, while the growth of prostate carcinoma as mostly originate from the peripheral zone. Greene et al reported that sonographic measurement and transitional zone volume (TZV) correlated with aging and clinical evidence of BPH. However, in that study parameters for evaluating BPH, that is symptoms, urine flow and urodynamics, were not reported. In addition, the relationship of the transitional zone relative to whole prostate volume [1][2][3][4][5][6] was not delineated.
The TZ index, that is the ratio of TZV to TV of the prostate, was reported by Kaplan et al in 61 patients to have a stronger statistically significant correlation with symptoms (r = 0,75, p = 0,001) and maximum urine flow (r = -0,71, p = 0,001) than with 7 prostate volume alone. Two other studies that was conducted by Kurita and Milonas have reported significant differences between patients with LUTS compared to BPH patients with urinary retention, and concluded that TZI can be used as a fairly accurate predictor to define risk of urinary retention, as treatment basis, either medical treatment or 8,9

surgery.
A study in Indonesia has already been done in determining the correlation between TZV, TZI, and TV with IPSS prostate, it that there is a significant correlation between TZV and TZI to the IPSS. Thus, came to the conclusion, degree of obstruction in patients with BPH are predictable Witjes et al investigated 150 patients using prostatic volume, TZ index and pressure flow studies, and failed to note any significant relationships. They believed that none of these parameters used alone was sufficient to diagnose bladder outlet obstruction (BOO). Lepor et al also reported that total prostate volume and TZ dimensions correlate poorly with symptoms and have inadequate correlations with BOO for clinical usefulness. Meanwhile Francoisi et al found low correlation between the score lower urinary tract symptoms assessed by IPSS and the different volumes of the prostate gland (TV, TZV) and prostate TZI, and, on the other hand, an inverse correlation between the intensity of urinary symptoms and QoL, supporting the idea of multifactorial aspects related to the pathogenesis of urinary symptoms in men. From these studies show that TZI is insufficient alone to provide the diagnosis

OBJECTIVE
This study evaluate the relationship between the IPSS score, Qmax, and degree of bladder outlet obstruction with transitional zone volume (TZV) and transitional zone index (TZI) in clinical BPH patient.

MATERIAL & METHOD
A cross sectional observational study of 26 clinical BPH patients between September 2011 until January 2012 (4 months) in the Outpatient Urology Clinic of Soetomo Hospital Surabaya. Inclusion criteria for this study were patients with BPH and LUTS with age over 50 years old and willing participate this study. While the exclusion criteria were patients clinically suggestive of prostate malignancy (PSA > 4 ng/dl) or bladder malignancies, patients who received alpha-blockers, 5á reductase inhibitor therapy, or previous prostate surgery. This study also excluded BPH patients with one or more abnormalities such as bladder stone, urethral stones, urethral strictures, diabetes mellitus, and neurological disorders. Data was analyzed descriptively and analytically. Prior to hypothesis testing, Kolmogorov-Smirnov test was performed for assessment of normal distribution. The relationship between TZV and TZI to IPSS, uroflowmetry, prostate volume and the degree of BOO were examined using the correlation tests.

RESULTS
We found the youngest patient was 53 years old and the oldest was 78 years old (table 1), with the mean age was 64,7 (± 5,98) years old. Nine patients (34,6%) came with mild complaints, 8 people (30,8%) came with moderate and the other 9 (34,6%) came with severe symptoms. Meanwhile, the mean IPSS in the study was15,15 (± 8,03). From the results we found 13 patients (50%) with maximum flow rate (Qmax) lower than 10 ml/sec, 11 patients (42,3%) with Qmax 10 -15 ml/s and 2 patients (7,7%) with Qmax more than 15ml/sec. Meanwhile the Qmax in this study was 9,59 (± 3,41) ml/s. Before correlation test performed to analyzed the data in this research, we performed the Kolmogorov-Smirnov test for normal distribution sample test. Results showed the variables are normally distributed, so the correlation test used in the study was Pearson correlation test.
The study examined the correlation between IPSS score with TV, TZV, and TZI. Using Pearson correlation analysis, a significant correlation between total IPSS with TV (r = 0,526, p = 0,006), TZV (r = 0,671, p = 0,000) and TZI (r = 0,812, p = 0,000) is found. In addition to the total score of IPSS, this study also performed correlation analysis between irritative and obstructive IPSS score with TV, TZI and TZV. All of this variables showed statistically significant correlation with IPSS (table 2).

DISCUSSION
Twenty six patients included in this study, the youngest was 53 years old, and the oldest was 78 years old. Overall mean age was 64,77 (± 5,98) years old. The similar group of age is obtained from the patients that were included to this study compared to the prevalence of BPH, 20% in 41-50 years old male, 50% in 51-60 years old male, and 90% in male older 14 than 80 years old.
Patients that were included in this research present with one of three categories of IPSS, 9 (34,6%) with mild category, 8 (30,8%) moderate, and 9 (34,6%) severe. Instrument recommended to assess clinical presentation of BPH with LUTS is IPSS; however, scores obtained by this instrument were often different from reality. Patients were able to mention the quantity of nocturia experienced correctly, but more likely to exaggerate frequency experienced from morning until afternoon, and score for intermittency and weak urine flow were often not similar to true events in IPSS scoring by the patients 15 themselves.
Data on maximum urine flow showed that 13 patients (50%) with Qmax < 10 ml/s, 11 patients (42,3%) with Qmax 10-15 ml/s, and only 2 (7,7%) with Qmax > 15 ml/s. Free uroflowmetry examination by Qmax was once thought to be the only examination to determine BOO, although interpretation is difficult especially in cases of BPH 16 with detrusor overactivity. Moreover, weak urine flow alone is nonconclusive as a diagnostic symptom of BOO, due to the fact that 25-30% of cases are caused by detrusor hypocontractility. Other study found that a normal urine flow, or even higher than normal flow (≥ 15 ml/s), 7% had proven to be obstructive. One research suggests that maximum urine flow rate does not have a significant high sensitivity and specificity. A study in 1998 was conducted by the International Continent Society on BPH. It shows that Qmax value has sensitivity of 70% and 47% of specificity in determining BOO. This research also shows that Qmax less than 10 ml/s only corrects on positive predictive value as much as 10%, thus free uroflowmetry can not be used as [16][17][18][19][20] single instrument to diagnose BOO.
Another variable recorded in this study was the degree of BOO which was done through examination of urodynamics pressure flow study and then interpreted based on the degree of obstruction according to Schaffer nomogram. There were no patients who came without obstruction, 19 patients (73,1%) had mild-moderate obstruction, and other 7 patients (26,9%) came with severe obstruction.
This research looks for the relationship between IPSS with TV, TZV, and TZI. From statistical tests, a significant relationship found between these variables (p < 0,05) (table 2). Complaints of LUTS in patients which included in this study, the obstructive, irritative and total, have increased in accordance to the increase in TV, TZV, and TZI. These results are similar to a study performed in 2004, which evaluated the relationship between prostate TZV, TZI, and TV with IPSS. From 49 men with LUTS complaints caused by BPH in this study, obtained a significant relationship between increasing of TZV, TZI, and prostate volume with increasing number of IPSS. But, this study only assessed relationship of TZV and TZI ** Significant correlation on level 0,01 (2-tailed) with subjective complaints without comparing other 10 BPH clinical variables. Another study analyzed relationship between TZV and TZI with IPSS and found stronger relationship between TZV with IPSS (r = 0,48, p = 0,03) and also between TZI with IPSS 7 (p = 0,001; r = 0,75). The strong relationship between TZI and IPSS are also shown in studies conducted by Lee et al. From the 58 patients with BPH who underwent TURP, a significant correlation was found between TZI by IPSS (p = 0,0001; r = 21 0,3652).
In addition to assess the relationship with the IPSS, Qmax was also considered to have correlations with TV, TZV, and TZI. In this study 50% of sample had Qmax < 10 cc/sec. From the correlation test using the Pearson test, we found that there were a weak correlation between the TZV with Qmax (r = -0,103, p = 0,616) and TZI (r = -0,084, p = 0,734) but this result was not statistically significant.
There are still various data in in determining the relationship between TZV and TZI to Qmax through free uroflowmetry in previous studies. Our results are similar to previous study conducted by Lepor  inconclusive.
Literature mentioned that TV of the prostate can not be used as a single examination to determine BOO. A retrospective study in 521 men showed poor 1 relationship between prostate volume with BOO. Because of the study, then several methods performed to refine the diagnosis of BOO in patients with BPH. TZI prostate showed a fairly strong relationship with BOO in 61 men with clinical parameters of BPH. This study also showed that the complaints of clinical BPH was significantly 7 elevated in patients with TZI of more than 0,50. Some researchs about TZI on BPH LUTS patients and urinary retention also show thatTZI has a significant correlation with clinical parameter of BPH and could be the predictor for urinary retention 8,9,21 and therapy outcomes.
There are different results concerning the correlation of TZI with some clinical parameters of [10][11][12] BPH, but the controversy might be caused by differences in research methodology used in choosing sample studies. Besides, the was multifactorial cause of LUTS which became one of the factor responsible for differences of the result. However, the consistency of inclusion and exclusion criterias could add a value to this research, although the research has smaller sample than the others.

CONCLUSION
TZV has correlation with IPSS score, but the correlation was not significant with Q max and BOO degree in BPH patient with LUTS. TZI has correlation with IPSS score and BOO degree, but not significant with Q max in BPH patient with LUTS. TZI could be performed as a single non invasive examination in clinics to determine the BOO in BPH patients with LUTS.