TOTAL PROSTATE SPECIFIC ANTIGEN RATIO FOR THE DIAGNOSIS OF PROSTATE CANCER

0022-5347/02/1671-0259/0 THE JOURNAL OF UROLOGY® Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC.®

Vol. 167, 259 –261, January 2002 Printed in U.S.A.

Letters to the Editor RE: SENSORY DISTURBANCE OF THE THIGH AFTER RENAL TRANSPLANTATION Y. Murata, K. Sakamoto, R. Hayashi, K. Takahashi, S.-I. Nakamura AND H. Moriya J Urol, 165: 770 –772, 2001 To the Editor. Ipsilateral thigh weakness may occur following renal transplantation due to femoral neuropathy. The authors prospectively studied renal transplant recipients to determine whether a component of sensory neuropathy also was present. They identified sensory femoral nerve disturbances in approximately 30% of the patients. The potential mechanisms for femoral neuropathy occurring during renal transplantation were reviewed, including possible ischemia to components of the femoral nerve due to either direct interference with blood supply, temporary occlusion of proximal blood supply or compression due to positioning the retractors. The authors noted that, although self-retaining retractors were not used in the majority of cases, sensory disturbances occurred in 30%. Temporary occlusion of the internal iliac artery in cases of direct anastomosis in an end-to-end fashion to the renal artery seems an unlikely cause of femoral neuropathy. The usual duration of vascular occlusion when performing arterial anastomosis is 20 to 30 minutes. Substantially longer intervals of vascular occlusion occur routinely in many forms of peripheral vascular surgery, including abdominal aortic aneurysm repair and aortofemoral bypass. However, motor or sensory neuropathy of the femoral nerve is infrequently described following those procedures. Before 1985 renal transplantation at our institution was performed with use of a Balfour rigid self-retaining retractor oriented with the blades placed on the superomedial and inferolateral aspects of the wound. Postoperatively renal transplant recipients occasionally had signs and symptoms of temporary motor and/or sensory neuropathy of the femoral nerve. These symptoms resolved with time in all instances. Beginning in 1985 we switched to use of a Bookwalter selfretaining retractor. Additionally, no retractor blade is placed on the inferolateral aspect of the wound where a retractor blade might compress branches of the femoral nerve against the anterosuperior iliac spine. Rather, a long 2-zero silk suture is placed through the inferolateral wound edge and the ends of the suture are wrapped around the ring of the self-retaining retractor. Since 1985 we have performed 932 renal transplantations in adults at our institution using the Bookwalter retractor as described. There has not been a single instance of clinically symptomatic motor or sensory femoral neuropathy since this change in technique was instituted. Based on our experience, I believe that nerve compression by retractor blades was the likely cause of occasional femoral neuropathy in our earlier experience. The described suture retraction technique along the lower edge of the incision avoids the potential for nerve compression against the anterosuperior iliac spine and affords easier exposure for performing the vascular anastomosis. Care must be taken in the placement of self-retaining retractor blades along the superomedial and superolateral portions of the wound to avoid nerve compression at this more proximal level.

examination or through careful interview. We discovered that sensory disturbance of the thigh can be caused by renal transplantation. Furthermore, in our study we placed no retractor blade on the inferolateral aspect of the wound, which Sagalowsky indicates is the cause of sensory disturbance. Therefore, retraction by silk suture may have some efficacy for another reason. In conclusion, we consider it necessary for Sagalowsky to conduct a neurological examination such as the pinprick test to confirm the efficacy of the silk suture method.

RE: A PROSPECTIVE STUDY TO EVALUATE THE ROLE OF COMPLEXED PROSTATE SPECIFIC ANTIGEN AND FREE/TOTAL PROSTATE SPECIFIC ANTIGEN RATIO FOR THE DIAGNOSIS OF PROSTATE CANCER I. D. C. Mitchell, B. L. Croal, A. Dickie, N. P. Cohen and I. Ross J Urol, 165: 1549 –1553, 2001

To the Editor. In this article the authors conclude from their calculations of significance levels for the receiver operating characteristic (ROC) curves that overall performance of the Bayer complexed prostate specific antigen (PSA) (Bayer Diagnostics, Tarrytown, New York) appears to be better than other PSA tests and ratios studied. However, so far it is only established that complexed PSA alone gives slightly better results in saving biopsies than total PSA alone.1 In some studies reported in 2000 that were not considered in this article various independent groups could not prove a significantly better performance of complexed PSA alone compared to free/ total PSA.2– 4 Furthermore, the unequal distribution of the already significantly different total PSA values between patients with benign prostatic hyperplasia (BPH) and those with prostate cancer leads to a better outcome in ROC analyses only for complexed PSA because of its excellent correlation to total PSA but not for other compared approaches like free/total PSA. This topic has been discussed in detail previously.5, 6 We recently evaluated the validity of ROC analyses regarding the effect of unequal total PSA distributions between patients with BPH and those with prostate cancer to assess the differential diagnostic performance of molecular forms of PSA.7 We recommend the matching procedure for total PSA values to avoid differences in total PSA concentrations between the 2 analyzed groups. All approaches of other molecular forms of PSA (free/total PSA, complexed PSA, ␣2macroglobulin PSA, ␣1-protease inhibitor PSA, BPH associated PSA or inactive zymogen PSA) should be compared in their ability to enhance diagnostic sensitivity or specificity only if total PSA is nearly identical in BPH and prostate cancer with areas under the ROC curves of approximately 0.5. We applied this matching approach in a recent multicenter clinical trial using a second generation ␣1-antichymotrypsin complexed PSA assay without the PSA gap, and in a comparison of this ␣1antichymotrypsin PSA test and the Bayer complexed PSA assay.8, 9 Respectfully, There was no significant advantage of the complexed PSA assay Arthur I. Sagalowsky Department of Urology alone (area under the ROC curve 0.59) or ␣1-antichymotrypsin PSA The University of Texas (0.64) compared to total PSA (0.53) except for the well-known better Southwestern Medical Center at Dallas clinical performance of free/total PSA (0.77) in distinguishing be5323 Harry Hines Blvd. tween BPH and prostate cancer.9 In addition, the same results were Dallas, Texas 75390-9110 obtained in a study of 97 patients with BPH or prostate cancer with total PSA less than 4 ng./ml.10 Therefore, we recommend using the matching procedure for calculating the areas under the ROC curves Reply by Authors. Did Sagalowsky or his staff neurologically ex- as indexes of the real statistical validity of such comparisons. We conclude that it is important to use similar methods in future amine the patients after surgery? In our study patients usually did not complain of any sensory disturbances. However, some were studies to compare the clinical performance of the different molecufound to have hypalgesia or paresthesia of the thigh on neurological lar forms of PSA or other kallikrein markers, such as human glan259

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LETTERS TO THE EDITOR

dular kallikrein/total PSA to avoid further misinterpretations of significance levels.

authors and, hence, the risk of urinary retention due to nerve injury would be minimized.

Respectfully, C. Stephan, K. Jung, D. Schnorr, M. Lein, P. Sinha and S. A. Loening Department of Urology and Institute for Laboratory Medicine University Hospital Charite´ Humboldt University Berlin Schumannstrasse 20/21 D-10098 Berlin, Germany

Respectfully, Mark R. Zaontz Section of Pediatric Urology University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School at Camden Three Cooper Plaza, Suite 411 Camden, New Jersey 08103-1439

1. Stamey, T. A. and Yemoto, C. E.: Examination of the 3 molecular forms of serum prostate specific antigen for distinguishing negative from positive biopsy: relationship to transition zone volume. J Urol, 163: 119, 2000 2. Okegawa, T., Noda, H., Nutahara, K. et al: Comparison of two investigative assays for the complexed prostate-specific antigen in total prostate-specific antigen between 4.1 and 10.0 ng/mL. Urology, 55: 700, 2000 3. Filella, X., Alcover, J., Molina, R. et al: Measurement of complexed PSA in the differential diagnosis between prostate cancer and benign prostate hyperplasia. Prostate, 42: 181, 2000 4. Jung, K., Elgeti, U., Lein, M. et al: Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer? Clin Chem, 46: 55, 2000 5. Stephan, C., Jung, K., Lein, M. et al: Re: Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer (letter to the editor). J Urol, 164: 1671, 2000 6. Stephan, C., Jung, K., Lein, M. et al: Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer. Cancer Epidemiol Biomarkers Prev, 9: 1133, 2000 7. Jung, K., Stephan, C., Lein, M. et al: Receiver-operating characteristic as a tool for evaluating the diagnostic performance of total prostate-specific antigen and its molecular forms—what has to be considered? Prostate, 46: 307, 2001 8. Lein, M., Jung, K., Hammerer, P. et al: A multicenter clinical trial on the use of alpha1-antichymotrypsin-prostate-specific antigen in prostate cancer diagnosis. Prostate, 47: 77, 2001 9. Lein, M., Jung, K., Elgeti, U. et al: Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis. Eur Urol, 39: 57, 2001 10. Jung, K., Stephan, C., Elgeti, U. et al: Molecular forms of prostate-specific antigen in serum with concentrations of total prostate-specific antigen ⬍4 ␮g/L: are they useful tools for early detection and screening of prostate cancer? Int J Cancer, 93: 759, 2001

1. Zaontz, M., Maizels, M., Sugar, E. C. et al: Detrusorrhaphy: extravesical ureteral advancement to correct vesicoureteral reflux in children. J Urol, 138: 947, 1987 2. Minevich, E., Aronoff, D., Wacksman, J. et al: Voiding dysfunction after bilateral extravesical detrusorrhaphy. J Urol, 160: 1004, 1998

Reply by Authors. We agree and regret that the statement that 26% of patients have bladder dysfunction after detrusorrhaphy is not quoted in the original publication of Zaontz et al. However, the other references cited in our publication confirm the high rate of bladder dysfunction after extravesical antireflux procedures, and our conclusion is not drawn from a single study. As demonstrated in our study, the higher risk of bladder dysfunction after detrusorrhaphy is caused by the circumferential myotomy and the Vest type sutures. Both steps will definitely destroy nerve fibers in the pelvic plexus. The dissection of the distal ureter is another step that carries the risk of nerve fiber damage. Therefore, every dissection of the distal ureter should be performed close to the ureter regardless of the antireflux technique used. Interestingly, after publishing our report, we have had a number of personal communications in which urologists have confirmed our conclusion. In these discussions our impression was that the incidence of bladder dysfunction may be even higher than that reported in our article. Many urologists told us that they had observed bladder dysfunction but did not realize others had experienced the same, since there are few data in the literature. In this context, we would like to encourage others to be aware of this complication and to report their own data to highlight the problem.

RE: BIOFEEDBACK TRAINING FOR DETRUSOR OVERACTIVITY IN CHILDREN T. Yamanishi, K. Yasuda, N. Murayama, R. Sakakibara, T. Uchiyama and H. Ito J Urol, 164: 1686 –1690, 2000

RE: THE PELVIC PLEXUS AND ANTIREFLUX SURGERY: TOPOGRAPHICAL FINDINGS AND CLINICAL CONSEQUENCES J. Leissner, E. P. Allhoff, W. Wolff, C. Feja, M. Ho¨ckel, P. Black, AND R. Hohenfellner J Urol, 165: 1652–1655, 2001 To the Editor. This is an interesting article that looks at the topography of the pelvic neural plexus with specific attention to nerve injury resulting from antireflux surgery. However, I noted that in the discussion they quoted an article I wrote on the detrusorrhaphy technique,1 and stated that voiding dysfunction required intermittent catheterization in 26% of patients. This is a misquote. In fact, in contradistinction to their statement, we performed bilateral detrusorrhaphy in 41 cases, of which only 1 case required intermittent catheterization for a short period. That case equates to 2.4% of this group and not 26%. The authors should not draw conclusions based on erroneous data. If one screens out those patients with significant voiding dysfunction, my experience and that of others are that bilateral detrusorrhaphy is, in fact, safe and effective, and has a low risk of urinary retention.2 Patient selection seems to be the most important parameter in determining the risk of postoperative urinary retention. The dissection to free up the ureter extravesically is done in line with the natural course of the ureter. By staying in this line, one would avoid the main portion of the pelvic plexus as described by the

To the Editor. The authors of this article conclude that biofeedback training is effective for treating detrusor overactivity. During biofeedback training, patients were instructed to contract the anal sphincter without raising abdominal pressure to inhibit overactive bladder contractions. The idea was that contracting pelvic floor muscles inhibits detrusor overactivity. We have recently described the mechanism of detrusor inhibition induced by contraction of the pelvic floor muscles.1, 2 By pelvic floor muscles we mean the puborectalis muscle, which is the constricting part of the levator ani muscle. The latter consists of the pubococcygeus, puborectalis and iliococcygeus, which are rudimentary in humans.3 While the pubococcygeus muscle on contraction opens the vesical and rectal necks, the puborectalis muscle closes them.4 – 6 The puborectalis muscle gives rise to the external anal and urethral sphincters.4, 5 When patients are instructed to contract the anal sphincter, the contraction of not only the external anal, but also the external urethral sphincter and puborectalis muscle will be affected. All 3 muscles contract simultaneously on anal sphincter squeeze.4, 5 Our previous studies have demonstrated that contraction of the anal or urethral sphincter or puborectalis muscle causes inhibition of rectal or vesical contraction, an effect mediated through the voluntary inhibition reflex.1, 2 The mechanism of evacuation starts with rectal or vesical contraction, which reflexively leads to internal sphincter relaxation provided the external sphincter relaxes. External sphincter contraction prevents relaxation of the internal sphincter. Failure of the latter to relax leads to reflex detrusor relaxation.1, 2 This reflex seems to be the mechanism by which the anal sphincter contraction, as performed by patients in biofeedback train-