ultrasonography-guided prostate biopsy protocol improvesthe detection of prostate cancer. Eur Urol, 45: 444, 2004

2. Presti, J. C., Jr.: Prostate biopsy: how many cores are enough?Urol Oncol, 21: 135, 2003

3. Eskicorapci, S. Y., Guliyev, F., Akdogan, B., Dogan, H. S., Er-gen, A. and Ozen, H.: Individualization of the biopsy protocolaccording to the prostate gland volume for prostate cancerdetection. J Urol, 173: 1536, 2005

4. Djavan, B., Ravery, V., Zlotta, A., Dobronski, P., Dobrovits, M.,Fakhari, M. et al: Prospective evaluation of prostate cancerdetected on biopsies 1, 2, 3 and 4: when should we stop?J Urol, 166: 1679, 2001

5. Vashi, A. R., Wojno, K. J., Gillespie, B. and Oesterling, J. E.: Amodel for the number of cores per prostate biopsy based onpatient age and prostate gland volume. J Urol, 159: 920,1998

6. Greene, K. L., Elkin, E. P., Karapetian, A., DuChane, J., Car-roll, P. R., Kane, C. J. et al: Prostate biopsy tumor extent butnot location predicts recurrence after radical prostatectomy:results from CAPSURE. J Urol, 175: 125, 2006

7. Eichler, K., Wilby, J., Hempel, S., Myers, L. and Kleijnen, J.:Diagnostic value of systematic prostate biopsy methods inthe investigation for prostate cancer. A systematic review.Available at http://www.york.ac.uk/inst/crd/pdf/report29.pdf

Re: Low Age Adjusted FreeTestosterone Levels Correlate WithPoorly Differentiated Prostate Cancer

I. F. San Francisco, M. M. Regan, W. C. DeWolfand A. F. Olumi

J Urol, 175: 1341–1346, 2006

To the Editor. Although the authors recognized the inad-equacy of a single determination to establish the degree ofandrogenism, an important issue not addressed by them orby the editorial comment accompanying the article refers tothe assay of testosterone. The measurement of free testos-terone (FT) is considered valid only if performed by equilib-rium dialysis or ultracentrifugation. Such methods are notreadily available, and are performed only in a handful ofcommercial laboratories in North America. In this study FTwas determined by radioimmunoassay (RI), which has beendismissed in the literature since 1997 as “seriously inaccu-rate, underestimating the true concentration (as estimatedby the equilibrium dialysis method) by manifold.”1–4

It may be argued that the inaccuracies were equally dis-tributed among groups (well vs poorly differentiated pros-tate cancer). The point I wish to raise is that FT determina-tion by RI should be abandoned in urological practice fordiagnosis of hypogonadism, assessment of possible effects oftestosterone in prostate health, and evaluation of therapeu-tic response to testosterone administration or androgen ab-lation (medical or surgical) in men with prostate cancer. Allcurrent methods except liquid chromatography have inter-pretational drawbacks. However, considering accuracy, costand availability, viable and reliable alternatives to FT by RIinclude bioavailable or calculated free testosterone. Finally,there is a need to increase physician awareness about themarked week-to-week variability within a single individual

even when the most accurate and practical methods areused.5

Respectfully,Alvaro Morales

Queen’s University and Centre forUrological Research

Kingston, OntarioCanada K7L 3J7

1. Tariq, S. H., Haren, M. T., Kim, M. J. and Morley, J. R.: Andro-pause: is the emperor wearing any cloths? Rev Endocr MetabDisord, 6: 77, 2005

2. Diver, M. J.: Analytical and physiological factors affecting theinterpretation of serum testosterone concentration in men.Ann Clin Biochem, 43: 3, 2006

3. Matsumoto, A. and Bremner, W.: Serum testosterone assays—accuracy matters. J Clin Endocrinol Metab, 89: 520, 2004

4. Rosner, W.: An extraordinarily inaccurate assay for free testos-terone is still with us. J Clin Endocrinol Metab, 86: 2903,2001

5. Morley, J. E., Patrick, P. and Perry, H. M., III: Evaluation ofassays available to measure free testosterone. Metabolism,51: 554, 2002

Reply by Authors. The comments by Morales are appreci-ated and speak to the difficulty of accurately measuringtestosterone levels in a clinical setting. First, equilibriumdialysis measurement of testosterone, although a more ac-curate test for FT, is an impractical test in the clinicalsetting because of the associated time and cost. In addition,equilibrium dialysis and bioavailable testosterone measure-ments were not readily available for our entire study cohortbetween 1995 and 2001.

Despite its inaccuracies, as cited by Morales, FT mea-sured by radioimmunoassay has a correlation coefficient of0.937 as compared to the equilibrium dialysis technique.1

Therefore, for retrospective correlative analyses, as in ourstudy, we believe FT measured by radioimmunoassay is stillvaluable for generating a hypothesis, and examining possi-ble links between hypogonadism and prostate cancer. Mov-ing forward, with prospectively designed studies we agreethat better standardized tests need to be used for evaluationof hypogonadism.

1. Vermeulen, A., Verdonck, L. and Kaufman, J. M.: A criticalevaluation of simple methods for the estimation of free tes-tosterone in serum. J Clin Endocrinol Metab, 84: 3666, 1999

Re: Single Center ExperienceWith Endoscopic Management ofVesicoureteral Reflux in Children

J. C. Routh, D. R. Vandersteen, H. Pfefferle,J. J. Wolpert and Y. Reinberg

J Urol, 175: 1889–1893, 2006

To the Editor. The management of primary vesicoureteralreflux continues to be controversial, with little consensusbetween physicians and surgeons about the role of surgery,let alone the ideal technique with which to treat reflux. TheMayo clinic team has presented a study on one of the aspects

LETTERS TO THE EDITOR2746

of reflux treatment, namely the use of injectable dextrano-mer/hyaluronic acid, in a group of 225 patients.

The accompanying editorial comment contains someadditional points worthy of further discussion. However,the publication does not refer to an important study of therelationship between reflux resolution and the configura-tion of the injected mound, nor does it allude to concernsabout substances that cause a granulomatous response,which may predispose to malignant transformation. In1995 we published a study that recorded 64 endoscopictreatments with polytetrafluoroethylene for vesico-ureteral reflux, which focused on the amount of polytet-rafluoroethylene paste used for injection at each treat-ment, the shape of the mound, the appearance of theorifice initially, the grade of vesicoureteral reflux andtreatment outcome.1 The cure rate was 86%, and theappearance of the mound of paste correlated well with theclinical outcome, except when less than 0.2 ml paste wasused for smaller ureteral orifices or when the ureteralorifice was large enough to admit the 9.3Fr cystoscope. Incases with a large ureteral orifice effective treatment wasachieved without the neat crescent-on-a-mound appearance,as long as a larger than average volume of paste was used.However, large volumes failed to treat a smaller orifice ifmeticulous placement of the needle had not occurred. Wewould recommend videotaping all of the injection treat-ments, and reviewing the reflux outcome and endoscopicappearance as part of continuous quality improvement.

Another point to address is the use of a foreign bodyimplant. Large foreign bodies have a higher incidence oftumor induction in the rat model, and reducing the par-ticle size and the duration of implantation minimizes therisk of malignancy.2 The predisposition appears to resultfrom the chronic inflammation with dextranomer/hyal-uronic acid, as is seen with polytetrafluoroethylene andsilicone. Our studies have indicated that the larger parti-cle injectable silicone is more likely to predispose to ma-lignancy than small particle polytetrafluoroethylene (asused in urology)3 but that silicone particles are also inad-vertently injected during routine pediatric intravenouspump infusion, and are ingested as a result of living in alarge city.4 Nevertheless, we would suggest that dextra-nomer/hyaluronic acid should be subjected to the samestudies conducted for polytetrafluoroethylene and siliconebut that the results should be put in the context of normalparticulate loading that results from living in moderncities.

Another point to note is the success rate of the injections.Many of the patients had grade I or II vesicoureteral reflux,giving a success rate of 54.1%, not 64%, for reflux that manybelieve does not warrant surgical management. Also, theseresults should be reviewed in light of the recently pub-lished data on the minimal pain experience associatedwith the open Cohen procedure without catheters, anoperation that can be performed as outpatient surgery inyounger patients.5

As we have previously contended, we have no doubt thatinjectable substances are able to resolve vesicoureteral re-flux. However, to establish the safety and appropriateness ofthe injection treatment, the long-term effect of the injectablesubstances should be studied, and we should expand the

research demonstrating the true role of surgery in enhanc-ing the well-being of these children.

Respectfully,Paddy Dewan

Urology UnitWomen’s and Children’s HospitalNorth Adelaide, South Australia

1. Dewan, P. A. and Higgs, M. J.: Correlation of the endoscopicappearance with clinical outcome for submucous Polytef in-jection in vesico-ureteric reflux. Aust N Z J Surg, 65: 642,1995

2. Dewan, P. A.: Is injected polytetrafluoroethylene (Polytef) car-cinogenic? Br J Urol, 69: 29, 1992

3. Dewan, P. A., Owen, A. J. and Byard, R. W.: Long-term responseto subcutaneously injected Teflon and silicone in a rat model.Br J Urol, 76: 161, 1995

4. Dewan, P. A., Hoebeke, P., Ehall, H., Chow, C. W., Edwards,G. A. and Terlet, J.: Migration of particulate silicone afterureteric injection of silicone. BJU Int, 85: 1, 2000

5. Chen, M., Dewan, P. A. and Anderson, P.: Analgesic require-ments for patients who had a ureteric reimplantation withcatheter drainage. Aust N Z J Surg, suppl., 72: 78, 2002

Reply by Authors. We should begin by correcting a signif-icant point. Although one of the authors of our study (JCR)is a resident in urology at the Mayo Clinic, all injectionswere performed at Children’s Hospitals of Minnesota. Thus,it is incorrect to refer to this series as that of the “MayoClinic team.”

Unfortunately, video recordings were not available for allinjections in our series, and, thus, we were unable to docu-ment objectively and uniformly the shape and size of theinjection mound. This problem is further complicated by thefact that to our knowledge no generally accepted method ofmound description has been published for dextranomer-hy-aluronic acid (Dx/HA) copolymer injection. However, Lavelleet al have confirmed the importance of this feature in acohort of patients undergoing subureteral Dx/HA injection.1

We agree with Dewan that video recording would provideexcellent data for quality control purposes.

In regard to the histological changes associated withDx/HA injection, we agree that further long-term studiesshould be performed to evaluate the safety of this substance.Stenberg et al have previously investigated Dx/HA in ani-mal models and in humans, with no short-term evidence tosupport injection related carcinogenesis.2,3 However, me-dium and long-term studies are required to verify thesefindings, and we are currently engaged in such studies.

We strongly agree that open ureteroneocystostomyshould still be considered the gold standard of antirefluxsurgical procedures, particularly in light of recently pub-lished data showing the validity of this approach as anoutpatient procedure.4 However, we would note thatDx/HA injection provides a good cure rate, albeit reducedin patients with higher grades of reflux. We believe thatthe minimally invasive nature of injection therapy and itslow complication rate justify its place in the armamentar-ium of the pediatric urologist, so long as it is not consid-ered a panacea and its limitations are recognized. Withinthis context it remains a useful tool for well selectedpatients.

LETTERS TO THE EDITOR 2747

1. Lavelle, M. T., Conlin, M. J. and Skoog, S. J.: Subureteralinjection of Deflux for correction of reflux: analysis of factorspredicting success. Urology, 65: 564, 2005

2. Stenberg, A., Larsson, E., Lindholm, A., Ronneus, B. and Lack-gren, G.: Injectable dextranomer-based implant: histopa-thology, volume changes and DNA-analysis. Scand J UrolNephrol, 33: 355, 1999

3. Stenberg, A., Larsson, E. and Lackgren, G.: Endoscopic treat-ment with dextranomer-hyaluronic acid for vesicoureteralreflux: histological findings. J Urol, 169: 1109, 2003

4. Putman, S., Wicher, C., Wayment, R., Harrell, B., Devries, C.,Snow, B. et al: Unilateral extravesical ureteral reimplanta-tion in children performed on an outpatient basis. J Urol,174: 1987, 2005

Re: The Impact of LatePresentation of Posterior UrethralValves on Bladder and Renal Function

O. Ziylan, T. Oktar, H. Ander, E. Korgali, H. Rodopluand T. Kocak

J Urol, 175: 1894–1897, 2006

To the Editor. The authors have reviewed the findings inpatients who present late with urethral obstruction, andlook for differences from the earlier presenting group. Acrossthe group they found that renal and bladder function wassimilar but they infer that there is a lesser degree of obstruc-tion in patients who present later. However, we would sug-gest that the variability of the condition is greater thansuggested in their article.

Our work, which was not referenced by the authors, hasshown 2 features of the variability of congenital obstructiveposterior urethral membrane (COPUM). The first feature, asHendren found,1 is a range in the appearance of the obstruc-tion endoscopically, which is a variable degree of the limita-tion of the posterior urethral lumen.2 The other variation wehave demonstrated is a variable degree of proximal radio-logical obstructive changes with similar changes on endo-scopic appearance of the COPUM.3 Thus, early and latepresenting patients can have a range of bladder and renalfunction outcomes.

We postulate that there may be different bladder reac-tions to the same limitation of the stream, a difference in thesecondary obstruction from distal prolapsing of the COPUMor perhaps different diseases that have a COPUM as acommon element. Study of the late presenting group in lightof the detailed endoscopic findings would be of interest, andwe thank the authors for their work.

Respectfully,Paddy Dewan

Urology UnitWomen’s and Children’s HospitalNorth Adelaide, South Australia

1. Hendren, W. H.: Posterior urethral valves in boys. A broadclinical spectrum. J Urol, 106: 298, 1971

2. Dewan, P. A. and Goh, D. G.: Variable expression of the con-genital membrane of the posterior urethra. Urology, 45: 507,1995

3. Dewan, P. A., Pillay, S. and Kaye, K.: Correlation of the endo-scopic and radiological anatomy of congenital obstruction ofthe posterior urethra and the external sphincter. Br J Urol,79: 790, 1997

Reply by Authors. We appreciate the commentary about ourarticle. However, there are several points to be clarified in thetext. In our series renal function was significantly impaired inthe late presenting group. Thus, what we tried to emphasize isthat it is not always true that late presentation is a morefavorable prognostic factor. Also, it may be misleading to de-scribe the obstruction as “lesser” in the late presenting group,because renal function was significantly affected in this group ofpatients. Bladder dysfunction was similar between the 2 groups.However, it was more pronounced in the late presenting patients.

We completely agree regarding the variability of ob-struction in patients with posterior urethral valves. How-ever, there are some difficulties in documenting the de-gree of obstruction. The interpretation of obstruction byendoscopic and radiological appearance is somehow a sub-jective analysis. The evaluation of voiding dynamics ob-tained by urodynamic studies may be a more reliableassessment. However, it also poses some technical chal-lenges.

Recently, in our clinic the endoscopic interventions of allpatients with posterior urethral valves have begun to berecorded routinely. The assessment of these findings couldlead to a better understanding of the pathophysiologicalprocess.

Re: A New Classificationis Needed for Pelvic PainSyndromes—Are ExistingTerminologies of SpuriousDiagnostic Authority Bad for Patients?

P. Abrams, A. Baranowski, R. E. Berger, M. Fall,P. Hanno and U. Wesselmann

J Urol, 175: 1989–1990, 2006

To the Editor. The 6 experts who authored this editorialare to be applauded for their forthright statement regardingthe deleterious effects of the use of conventional terminologyfor “diagnostic” authority in patients with chronic pelvicpain (CPP). The descriptive terms and symptoms used inthis editorial are in the “territory” of the pudendal nerve.Fall et al have made brief reference to pudendal neuropathyin the European Association of Urology guidelines onchronic pelvic pain.1 However, no such reference was madein this editorial.

Previous articles in The Journal of Urology® demon-strate the neuropathic issues affecting CPP. Ricchiuti iden-tified abnormal neurophysiological testing in a cyclist withperineal pain.2 Amarenco and Kerdraon presented a schol-arly discussion of pudendal nerve neurophysiological test-ing.3 Relief of CPP can be achieved using pudendal nerveblocks of local anesthetic and triamcinolone.4 Indeed, in thesame issue as the editorial the pelvic symptoms that Cohen

LETTERS TO THE EDITOR2748