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BPH Importance of prostate volume and urinary flow rate in prediction of bladder outlet obstruction in men with symptomatic benign prostatic hyperplasia

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BPH Importance of prostate volume and urinary flow rate in prediction of bladder outlet obstruction in men with symptomatic benign prostatic hyperplasia
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  Central european Journal of urology   2011/64/2 75   Central european Journal of urology   2011/64/2 75 BpH IntroDuCtIon Benin prostatic enlarement (BPE), bladder outlet obstruction (BOO) and lower urinar tract smptoms (LUTS) is the basic triad for clinical dianosis of benin prostatic hperplasia (BPH) [1]. BPH is rare in men ouner than 40, but is present in up to 50% of men over 60 ears of ae and nearl 88% b 80 ears of ae [2, 3]. Mac-roscopic enlarement of the land is found in almost half of men who have microscopic BPH. Smptoms caused b BPH and named LUTS, can be cateo-rized as obstructive (voidin) and irritative (storae). Obstructive smptoms are caused b enlarement of the phsical mass of the land (static component) as well as tone of smooth muscle of the prostatic stroma (dnamic component). Irritative smptoms are associated with the bladder dsfunction caused b BOO [4]. It has been estimated that 25% of men in their sixth decade of life have urinar smptoms and objective sins of BOO [2]. However, the evidence for a direct link between BPE, BOO, and LUTS is far from convincin [4, 5].The aim of surical treatment for BPH is to relieve or eliminate BOO. Most patients with LUTS and an enlared prostate will benet from prostatectom; however, part of them still experience per-sistent storae smptoms [4]. Fifteen to 30% of the patients with BPH do not have a favorable outcome after transurethral resection of the prostate (TURP) if smptoms are considered [6]. One of the main causes of unfavorable results is absence of obstruction before surer. Pressure-ow urodnamic studies remain the most denitive method of objective documentin BOO. It serves as the best instru-ment to nd out if the smptoms are caused b prostatic obstruc-tion or bladder dsfunction [7]. Preoperative investiations with pressure-ow stud has been demonstrated that 20-50% of pa-tients with LUTS had no urodnamic evidence of obstruction [7-9]. However suitabilit of urodnamics in assessin BPH is controver-sial in terms of invasiveness, cost, time consumption, and, both, reproducibilit and variabilit of results [7]. Therefore these studies still are not routinel recommended in BPH.It has been proven that the dianosis of BOO cannot be made b smptomatic assessment alone [8]. Size of prostate and post-void residual (PVR) of urine are important in evaluation of BPH, but not critical for dianosis of obstruction. It has been conrmed b studies that the best sinle predictor of BOO is urinar ow rate. Approximatel 70% of men with peak ow rate (Qmax) less than 15 ml/s are obstructed [10]. Value of other parameters of free ow is more controversial. Recent studies show that ultrasound estimated prostate weiht or prostate transition zone volume can also predict obstruction [11, 12].Better prediction of obstruction usin parameters of non-invasive investiations aimed to improve results of BPH surer is an important topic for more than two decades, but there is no worldwide-accepted model. Some studies show that predictabil-it of conventional tests alone or in combination for BOO is onl 60-70% [13]. The aim of our stud was to look for possibl better simple predictors. key worDs prostate volume »  urinar flow rate »  bladder outlet obstruction »  benin prostatic hperplasia »  pressure/flow stud   aBstraCt objciv.  To predict bladder outlet obstruction with parameters of non-invasive investiations for patients with smptomatic benin prostatic hperplasia. pi d mhd. A sample of 122 men with moderate to severe lower urinar tract smptoms su-estive of benin prostatic hperplasia was selected. Transrectal prostate ultrasound, free flow measurement, and transabdominal ultrasound for residual urine were carried out toether with diital rectal examination for all patients. All patients underwent urodnamic pres-sure/flow test. Two roups of obstructed (91 patient) and equivocal/unobstructed (31 patient) were analzed. Probabilistic model based on loistic reression was developed for prediction of obstruction. r.  Various parameters were compared in obstruct-ed and non-obstructed/equivocal roups, hihliht-in important parameters for obstruction. Correlation analsis indicates hiher obstruction dependence on averae and peak flow rates and lower dependence on total prostate and transition zone volumes, transition zone index. Binar loistic reression model suests that averae flow rate combined with total prostate vol-ume is the best predictor of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analzed sample. The analzed model suests that peak flow rate could also be almost equall important parameter instead of averae flow rate. Cci.  The stud suests that averae/peak flow rate combined with total prostate volume can be used for prediction of obstruction. The developed probabilistic model helps to determine patients who need invasive urodnamic testin for decision on surical treatment. Imc   vm d i   i dici  bdd  bci i m ih mmic bi ic hi Drius trumbecs  1 , Dimns Milons  1 , Mindus Jievls  1 , aivrs Jons Mjosiis  1 , Mrius kincius  1 , aivrs grybs  1 , Vyis kopusinss  2    1 Clinic of Urolo, Lithuanian Universit of Health Sciences, Kaunas, Lithuania 2 Centre of Statistics, Universit of Vtautas Manus, Kaunas, Lithuania    Central european Journal of urology   2011/64/2  76   DARIUS TRUMBECKAS, DAIMANTAS MILONAS, MINDAUgAS JIEVALTAS, AIVARAS JONAS MATJOSAITIS, MARIUS KINCIUS, AIVARAS gRyBAS, VyTIS KOPUSTINSKAS MaterIal anD MetHoDs There were 122 men aed 45-85 ears with moderate to severe LUTS suestive for BPH involved in this prospective stud durin the period from March 2003 to December 2004. Permission for the stud was obtained from the Reional Ethics Committee. Informed consent was received from all patients. Onl subjects with Interna-tional Prostate Smptom Score (IPSS) ≥ 7 and Qmax in rane 3-20 ml/s in total voided volume of 120 ml or reater were included. Smptoms were measured accordin IPSS toether with qualit of life (QoL) question. All uroow traces were reviewed b a sinle investiator for correction of artifacts.Individuals who had underone previous prostate or lower uri-nar tract surer or who had prostate cancer or PSA level exceed-in 10 n/ml were excluded. Carcinoma of the prostate in case of PSA rane 4 to 10 n/ml had to be excluded b prostate biops. Pa-tients with bladder stones, urinar tract infection, and suprapubic drainae as well as evidence of neuroenic bladder were excluded from the stud. Uroowmetric free urinar ow measurement (Urodn 1000, Medtronic) was performed for ow parameters. Prostate size was measured b transrectal ultrasound (Siemens Sonoline SI-250 with probe of 5-7.5 MHz) evaluatin total prostate volume (TPV) as well as transition zone volume (TZV). For calculation of prostate volume, the ellipsoid formula (0.52 x width x heiht x lenth) was used [14]. Transition zone index (TZI) was calculated b dividin TZV/TPV. Post void residual (PVR) was measured b transabdominal ultrasound usin bladder measurements in transverse and saittal plains im-mediatel after free ow measurement. Eventuall all patients un-derwent urodnamic pressure-ow stud (Duet ®  Loic, Medtronic, software Duet 8.37, 1995-2001 Medtronic Functional Dianostics A/S). Bladder llin with subsequent pressure-ow stud was per-formed in rate of 30 ml/min with 37°C saline via transurethral two-channel 7 F urodnamic catheter. The test was repeated two times and lower deree of obstruction showin data was taken to account. The International Continence Societ (ICS) nomoram was used for obstruction evaluation. Accordin to this nomoram the patients were classied into two roups: obstructed (Abrams-grifths number – Ag >40) and unobstructed/equivocal (Ag ≤ 40).   Comparin to Schafer nomoram these roups were separated b line between cateories two and three. Urodnamic studies were performed and evaluated accordin ICS recommendations b one investiator (DT).Statistical analsis was performed usin SPSS software. Mean, standard deviation (SD), 10-90 percentiles, median, and correlation coefcients (r) were calculated. Sinicant differences in roups were analzed b t-test for independent normall distributed samples and b Mann-Whitne U test for non-normall distributed samples. The binar loistic reression model was developed for obstruction probabilit estimation and identication of the most important predictors. A level of statistical sinicance was chosen to be 95%. results There were 91 obstructed and 31 unobstructed/equivocal out of 122 tested patients. Ae of patients was not statisticall dif-ferent between the roups (p = 0.088). Qmax in rane of 4-15 ml/s was determined in 85.3% of patients. The characteristics of parameters for both roups are summarized in Table 1. A statisti-call sinicant difference between the roups was reached for total IPSS score, score of obstructive smptoms evaluated b ques- tb 1. Characteristics of obstructed and unobstructed/equivocal patients a i,  = 122obcd,  = 91ubcd/qivc,  = 31-vMsD10-90 ciMdiMsD10-90 ciMdiMsD10-90 cimdi Ae (ears)67.68.558.0-77.768.568.48.159.0-79.06965.49.351.5-76.8660.09Duration of smptoms (ears)5.13.81.0-10.04.05.03.51.0-10.04.05.54.81.1-12.44.00.99Irritative smptoms (2,4,7 of IPSS)7.63.34.0-12.07.07.73.24-127.07.23.53-137.00.34Obstructive smptoms (1,3,5,6 of IPSS)10.55.04.3-18.710.011.24.75-1911.08.35.12-167.00.002IPSS18.06.810.0-27.017.018.96.610-2919.015.46.58-2614.00.01QoL3.91.32-64.04.01.32-64.03.51.12-540.04PSA (n/ml)3.63.10.9-7.62.63.93.20.9-7.92.92.82.50.8-6.91.90.05Post void residual (ml)76.588.02-21345.087.193.06-23450.045.663.20-12230.00.002Total prostate volume (ml)53.832.124.9-84.945.558.834.228.0-89.850.039.218.317.2-70.033.00.001Transition zone volume (ml)28.624.86.5-50.723.632.626.59.4-56.326.816.813.43.5-36.812.00.0001TZI0.480.150.28-0.660.490.510.130.33-0.680.510.380.140.16-0.600.400.0001Qmax free (ml/s)10.14.55.2-16.89.28.83.75.0-13.38.213.65.07.5-19.413.40.0001Qave free (ml/s)5.22.52.7-8.84.54.41.92.3-6.34.07.32.93.8-11.37.60.0001Ag number67.737.125.0-120.365.682.531.047.3-127.777.824.910.411.7-36.128.00.0001pdetQmax (cm/H 2 O)85.533.347.3-135.280.097.829.461.2-142.894.049.49.834.2-62.651.00.0001IPSS – International Prostate Smptom Score, QoL – Qualit of Life score, TZI – transition zone index (transition zone volume/total prostate volume), Qmax free – free peak ow rate, Qave free – free averae ow rate, Ag number – obstruction number, if over 40 – obstruction (Ag number = pdetQmax – 2 Qmax), pdetQmax – detrusor pressure at peak ow). p - values were calculated to test sinicant differences between the roups (difference considered statisticall sinicant if p <0.05), SD – standard deviation.   Central european Journal of urology   2011/64/2 77 IMPORTANCE OF PROSTATE VOLUME AND URINARy FLOW RATE IN PREDICTION OF BLADDER OUTLET OBSTRUCTION IN MEN WITH SyMPTOMATIC BENIgN PROSTATIC HyPERPLASIA tions 1, 3, 5, and 7 of IPSS, TPV, TZV, TZI, peak (Qmax) and averae (Qave) ow rates, as well as PVR. These variables correlated with the deree of obstruction evaluated b the Ag number, but hih correlation was observed onl with Qave and Qmax (r respectivel -0.501 and -0.496, p = 0.0001). Ag number correlated with TZI (r = 0.29, p = 0.001), total prostate and transition zone volumes (r = 0.27 for both, p = 0.003) as well. Correlation with residual urine was considerabl lower (r = 0.198, p = 0.03). No statisticall si-nicant correlation between ae of patients and obstruction was observed. Loistic reression model suests that obstruction is best predicted when combination of Qave and TPV are used. Overall pronostic power of this combination for detectin correct results was 83% (with probabilit cut value of 0.6). PPV (positive predictive value) = 92%; NPV (neative predictive value) = 52%. Pronostic power for prediction of obstruction in the rst roup reached 91%. Unobstructed/equivocal subjects were predicted correctl in 61% of cases in the second roup. Analsis of odds ratio (OR) for each variable shows that in case of Qave and TPV it was respectivel 0.61 (95% CI 0.49-0.76) and 1.04 (95% CI 1.01-1.07). It means that increase of Qave b 1 ml/s decreases obstruction probabilit b 1.6 times and increase of total prostate volume b 1 ml increases it b 1.04.The developed binar loistic model for prediction of obstruc-tion is the followin: ,where P – probabilit of obstruction;z = 2.149 + 0.037   TPV – 0.501 QaveIt can be calculated that in case of total prostate volume 40 ml and Qave 5 ml/s probabilit of obstruction equals to 0.75 (75%). Predictive power of Qmax in combination with TPV was slihtl lower – small difference is seen onl in the roup of unobstruct-ed/equivocal subjects (58% of correct predictions) with the al-most same rate of correct results in total and in the roup with obstruction. Compatibilit of model with the data (Cox Snell and Naelkerke coefcients of determination) was slihtl lower in case of Qmax and TPV. Equation for prediction of obstruction with Qmax in combination with TPV is the followin: ,where z = 1.952 + 0.039 TPV – 0.249 QmaxCombinations of TZV or TZI with Qmax or Qave were not supe-rior in prediction of obstruction compared to TPV. The free ow pattern of a patient with TPV of 51 ml (Fi. 1) and computer based calculation of obstruction probabilities (Fi. 2) are presented. Chanes in obstruction probabilit due to value of parameters are shown in Fis. 3 and 4. Fi. 3 visualizes obstruc-tion probabilit as function of averae ow rate and TPV. Fiure 4 presents isolines of selected obstruction probabilit. Fiure 4 also visualizes the area of obstruction probabilit bein more than 0.9 isoline (upper left corner of the plot). DIsCussIon In face of numerous micro-invasive techniques for BPH treat-ment, transurethral resection is still the main and the best option. TURP is performed in approximatel 95% of surical procedures and open procedures are reserved onl for ver lare prostates [15]. fi. 1.  Uroowmetric trace of a 59-ear-old patient with total prostate volume of 51 ml: peak ow rate 18.4 ml/s, averae ow rate 10 ml/s. fi. 2. Obstruction predicted for the same 59-ear-old patient. Total prostate volume 51 ml, peak ow rate 18.4 ml/s, averae ow rate 10 ml/s. Probabilit of obstruction 27-35%. fi. 3. Bladder outlet obstruction probabilit dependence on total prostate vol-ume (TPV) and averae ow rate (Qave). fi. 4. Bladder outlet obstruction probabilit isolines due to total prostate vol-ume (TPV) and averae ow rate (Qave).  VibtpV (cc) 51Qv (m/) 10Qmx (m/) 18.4Imdi cci-0.97 -0.64pbbii  bci ccdi Qv 0.27pbbii  bci ccdi Qmx 0.35  z  z  ee P  += 1  z  z  ee P  += 1  Central european Journal of urology   2011/64/2  78   DARIUS TRUMBECKAS, DAIMANTAS MILONAS, MINDAUgAS JIEVALTAS, AIVARAS JONAS MATJOSAITIS, MARIUS KINCIUS, AIVARAS gRyBAS, VyTIS KOPUSTINSKAS In the Department of Urolo at Kaunas Medical Universit Hospital, 150-160 prostatectomies due to BPH are performed annuall, TURP comprise 60-70%. Thouh TURP is an effective procedure with ood or excellent results in 80-85% of cases [6, 16, 17], the pos-sibilit of an unfavorable outcome is still hih. One of reasons for unfavorable results is unsatisfactor preoperative selection of pa-tients. Prediction of obstruction in terms of postoperative effect would be of most important value.Accordin to literature, the most valuable parameter for pre-diction of obstruction is peak ow rate (Qmax). In case of Qmax <10 ml/s, likelihood of obstruction is 90%, in rane of Qmax 10-14 ml/s – 67% and in Qmax >15 ml/s – onl 30% [15]. Approximatel 1/3 of patients with Qmax over 10 ml/s are unobstructed. Probabilit of obstruction in case of Qmax >10 ml/s for elderl man (>80 ears) falls to 40% [15]. In some studies, on the basis of uroow alone, 21% of the patients were misclassied [6]. Sinle or combined con-ventional tests can predict correctl just in 60-70% of cases [13]. Accordin to our stud, misclassications in 21-25% is possible if onl a sinle free ow parameter, Qmax or Qave, is used.Traces of uroow often have peaks and reistered Qmax is not reliable. Such artifacts need to be corrected. Averae ow rate is a quite stead parameter and should be important in case of con-tinuous ow without terminal dribblin [3]. Our stud shows, that Qave predicted obstruction even better than Qmax, but the differ-ence compare to Qmax was not pronounced. Combination of Qave and TPV had the best predictive power in our sample. Combinations of Qmax – TPV or Qmax – TZV were not superior. As has been shown in man of studies PVR is not important predictor of obstruction. Our data also conrm that post-void re-sidual volume is not of paramount importance in terms of obstruc-tion. Thouh we found statisticall sinicant difference for PVR between the roups, correlation of PVR with obstruction was weak. Predictive models usuall use PVR as one of important parameters (Clinical Prostate score model developed b Rosier et al. as well as models developed b Van Venrooij et al. and Madersbacher S. et al.), but we did not nd its importance for prediction [8]. A bi volume of residual urine indicates bad detrusor contractilit rather than obstruction [10]. From the other hand, bad contractilit shows terminal phase of obstructive process. Transition zone volume more than total prostate volume repre-sents processes of benin hperplasia. Therefore, measurement of transition zone volume is essential, especiall in terms of treatment options [12]. Transition zone volume correlates well with resected volume of the prostate [12]. It was shown b studies of Kaplan that transition zone volume is directl associated with urodnamic ob-struction of the bladder and this correlation is mostl reliable when transition zone index is over 0.5 [11]. Thouh it was shown that transition zone index is important on prediction of outcome after TURP [17], recent stud did not conrm superiorit of TZV or TZI for prediction of urodnamic obstruction compare to TPV.There are less correct predictors in the roup of unobstructed/equivocal subjects, which directl worsens total rate of correct pre-dictions. Better prediction in this roup would be ver important because it would let us improve surical results. Unfortunatel there are no clear parameters for prediction of bad contractilit/unobstructed. We uess that in case of calculated probabilit of obstruction 0.4-0.8, an invasive urodnamic pressure/ow stud would be benecial, especiall if surical treatment is considered (Table 2). Thouh combination of Qmax and TPV was not superior, the predictive power of it was almost the same as Qave combined with TPV. Considerin ow pattern either Qave or Qmax should be used. Probabilities should be calculated usin both models and results compared. We suppose that similar results show reliable pronosis. In case of difference, uroowmetr should be repeated and prob-abilities re-evaluated. Pronounced difference and/or probabilit around 0.5 would be indicative for invasive pressure ow stud. In case of hih probabilit of obstruction, urodnamic pressure ow stud could be spared. Our stud shows that Qave is as ood as Qmax and can be used more often. ConClusIons A binar loistic reression model was developed, which su-ests that averae ow rate and total prostate volume are the best predictors of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analzed sample. The analzed model suests that peak ow rate could also be an almost equall important pa-rameter instead of averae ow rate. The above parameters could be obtained from simple ultrasound and free ow measurements. The developed probabilistic model also provides information that is useful to select patients who need invasive urodnamic testin for decision on surical treatment. It is suested to perform invasive urodnamic testin in case obstruction probabilit is in the rane of 0.4-0.8. referenCes 1. Pesce F, Rubilotta E, Rihetti R et al: Results in 522 patients assessed in a ‘ow-clinic’.  Urodinamica   2002; 12: 144-145. tb 2.  Approximate probabilities of bladder outlet obstruction Qv (m/)t  vm (m)2030405060708090100 20.870.910.930.950.970.980.980.990.9930.8*0.850.890.920.950.960.970.980.9940.71*0.78*0.840.880.910.940.960.970.9850.59*0.68*0.75*0.820.870.90.930.950.9760.47*0.56*0.65*0.73*0.8*0.850.890.920.9470.350.44*0.53*0.62*0.7*0.77*0.830.880.9180.250.320.41*0.5*0.59*0.68*0.75*0.810.8690.170.220.290.380.47*0.56*0.65*0.73*0.79*100.110.150.20.270.350.43*0.52*0.62*0.7**suested indication for pressure/ow stud; Qave – averae ow rate   Central european Journal of urology   2011/64/2 79 IMPORTANCE OF PROSTATE VOLUME AND URINARy FLOW RATE IN PREDICTION OF BLADDER OUTLET OBSTRUCTION IN MEN WITH SyMPTOMATIC BENIgN PROSTATIC HyPERPLASIA 2. Lepor H, Lowe FC: Evaluation and nonsurical manaement of benin prostatic hyperplasia  . In: Walsh PC, Retik AB, Vauhan ED, Wein AJ, eds, Campbell’s Urolo CD-ROM, 8 edn, Vol. 2. Chapt 39. Philadelphia: Saun-ders, 2003.3. Chaple CR, MacDiarmid SA. Voidin difculty  . In: Chaple C, MacDiarmid S, eds, Urodnamics. Made eas, 2 edn, Vol. 1. Chapt 4. London: WB Saunders, Harcourt Publishers Limited 2000, pp. 75-76.4. Andersson KE: Storae and voidin symptoms: pathophysioloic aspects  . Urolo 2003; 62 (5 Suppl. 2): 3-10.5. Shapiro E, Lepor H: Pathophysioloy of clinical benin prostatic hyperpla- sia  . Urol   Clin   North   Am 1995; 22 (2): 285-290.6. Rollema HJ, Van Mastrit R: Improved indication and follow-up in tran- surethral resection of the prostate usin the computer proram CLIM: a prospective study  . J Urol 1992; 148 (1):111-115.7. Te AE, Kaplan SA: Urodynamics and benin prostatic hyperplasia  . In: Kirb R, McConnell J, Fitzpatrick J, Roehrborn C, Bole P, eds, Textbook of Be-nin Prostatic Hperplasia Vol. 1. Oxford: Isis Medical Media LTD 1996, pp. 187-198.8. Madersbacher S, Klinler HC, Djavan B et al: Is obstruction predictable by clinical evaluation in patients with lower urinary tract symptoms?   Br J Urol 1997; 80 (1): 72-77.9. Rodriues P, Lucon AM, Freire gC, Arap S: Urodynamic pressure ow studies can predict the clinical outcome after transurethral prostatic resection  . J Urol 2001; 165 (2): 499-502.10. Jepsen JV, Bruskewitz RC: Comprehensive patient evaluation for benin prostatic hyperplasia  . Urolo 1998; 51 (Suppl. 4A): 13-18.11. Kaplan SA, Te AE, Pressler LB, Olsson CA: Transition zone index as a method of assessin benin prostatic hyperplasia: correlation with symptoms, urine ow and detrusor pressure  . J Urol 1995; 154 (5):1764-1769.12. Milonas D, Trumbeckas D, Juska P: The importance of prostatic measur- in by transrectal ultrasound in surical manaement of patients with clinically benin prostatic hyperplasia  . Medicina (Kaunas) 2003; 39 (9): 860-866.13. Homma y, gotoh M, Takei M, Kawabe K, yamauchi T: Predictability of con- ventional tests for the assessment of bladder outlet obstruction in benin prostatic hyperplasia  . Int J Urol 1998; 5 (1): 61-66.14. Proto Wg: Protocols for the evaluation of therapies in BPO. Other assessments: prostate size and prostate specic antien  . Br J Urol 2000; 85 (Suppl 1): 31-35. 15. de la Rosette JJ, Perachino M, Thomas D et al: guidelines on Benin Pros- tatic Hyperplasia  . European Association of Uroloy / Conference Proceed- in   2001: 1-63. 16. Milonas D: The inuence of clinical factors on the outcome of surical treatment of benin prostatic hyperplasia  . Thesis/Dissertation, Kaunas Universit of Medicine, 2004: 97-98. 17. Milonas D, Jievaltas M, Trumbeckas D: Transition zone index – the most im- portant preoperative parameter on prediction outcome after transurethral resection of the prostate  . Eur   Urol   Suppl 2005; 4 (3): 257-257. Cdc Darius TrumbeckasClinic of UroloHospital of Lithuanian Universit of Health Scienes Kaunas ClinicsEiveniu 2LT-50009, Kaunas, Lithuaniaphone: +37 037 326 090trumbeckas@mail.com
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