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Re: Safety and Tolerability of Tolterodine for the Treatment of Overactive Bladder in Men With Bladder Outlet Obstruction
LETTERS TO THE EDITOR reported their experience with 108 and 46 consecutive laparoscopic sacral colpopexies, respectively. These authors observed posterior vaginal wall defect recurrence and/or development exclusively among patients who underwent sacral colpopexy with a concomitant Burch colposuspension unrelated to the placement or otherwise of a posterior mesh. However, they did not observe any posterior vaginal wall defect recurrence and/or development following sacral colpopexy with concomitant placement of tension-free vaginal tape.2 Although it is evident that more studies are needed before any reliable conclusions can be drawn, the authors should have discussed this important point in their article. At the present time an increasing number of laparoscopic abdominal sacral colpopexy procedures are being performed all over the world. Surgeons must be aware of the increasing risk of posterior vaginal wall defect development when a concomitant Burch procedure is performed. Respectfully, Xavier Deffieux Department of Obstetrics and Gynecology Antoine Beclere Hopital Clamart, France Reply by Authors. We agree that the role of Burch colposuspension in the development of posterior compartment prolapse is an important issue that reconstructive surgeons must be aware of. Our study did not directly address this issue. In our series we did not observe a difference in the occurrence of posterior prolapse following the Burch procedure compared to bladder neck slings. Baessler and Stanton did not detect a difference in the development of posterior prolapse in women undergoing sacrocolpopexy who underwent a Burch procedure compared to those who did not.3 When examining this issue in these complex cases a number of factors must be considered. The placement of posterior mesh, concomitant culdoplasty and perineal body repair are factors that may be at least as important in the development of posterior prolapse as the Burch procedure itself. The lack of homogeneity between surgeons in performing these procedures best explains the discrepancy in data. We are currently performing mid urethral slings in all of these patients with stress urinary incontinence, since we believe this procedure has a number of advantages over a Burch procedure. We agree with Deffieux that surgeons who perform Burch procedures with sacral colpopexy procedures should be aware of a possible increased potential for recurrent posterior prolapse. 1.
2.
3.
Antiphon, P., Elard, S., Benyoussef, A., Fofana, M., Yiou, R., Gettman, M. et al: Laparoscopic promontory sacral colpopexy: is the posterior, recto-vaginal, mesh mandatory? Eur Urol, 45: 655, 2004 Gadonneix, P., Ercoli, A., Salet-Lizee, D., Cotelle, O., Bolner, B., Van Den Akker, M. et al: Laparoscopic sacrocolpopexy with two separate meshes along the anterior and posterior vaginal walls for multicompartment pelvic organ prolapse. J Am Assoc Gynecol Laparosc, 11: 29, 2004 Baessler, K. and Stanton, S. L.: Sacrocolpopexy for vault prolapse and rectocele: do concomitant Burch colposuspension and perineal mesh detachment affect the outcome? Am J Obstet Gynecol, 192: 1067, 2005
2311
Re: Safety and Tolerability of Tolterodine for the Treatment of Overactive Bladder in Men With Bladder Outlet Obstruction P. Abrams, S. Kaplan, H. J. De Koning Gans and R. Millard J Urol, 175: 999 –1004, 2006 To the Editor. This publication contains some errors that I would like to discuss. First, I find it remarkable that in a publication about the “safety and tolerability of tolterodine for the treatment of overactive bladder [OAB]” no new or useful information about the treatment of OAB is found. The data and conclusions are limited to the statement that it is not dangerous to administer tolterodine to men with OAB because it does not adversely affect urinary tract function and these men find it tolerable. But is this convincingly demonstrated? And is there any improvement in OAB, ie is there any benefit? There is no explicit analysis of the drug trial data with respect to improvement of OAB, ie of the bothersome symptoms of urgency, urge incontinence, increased frequency and nocturia. I found urodynamic data indicating that some urodynamically measurable aspects of OAB may not have improved with tolterodine. Such data are volume at first detrusor contraction (which can be taken as an indicator of urgency) and volume at maximum bladder capacity (which can be taken as an indicator of frequency). The potential benefit from the reported increases in volumes for these 2 key OAB symptoms seems lost because of the increase in post-void residual (PVR) volume. It is difficult to see how a patient could benefit from a larger bladder capacity when the voided volume increases little or not at all due to an increase in residual volume. Unfortunately, this aspect is not discussed in the article. I doubt that the statement that these volume increases “favor[ing] tolterodine over placebo” will stand if the PVR increase is properly taken into account. These doubts are confirmed by the decrease in voiding efficiency, which was statistically significant. My second problem with this publication is that I am not convinced that the urodynamic data are properly analyzed and interpreted, either by the concept of testing for equivalence of changes in peak urinary flow rate (Qmax) and detrusor pressure at maximal flow rate (pdetQmax), or by the methodology based on the Abrams factors. I do not think it is meaningful to compare Qmax and pdetQmax as primary end points without taking significant changes and/or differences in bladder filling volume into account. Such volume changes could have been expected and are reported with tolterodine as being significant. An increase in Qmax and, dependent on the type of obstruction, some increase in pdetQmax are to be expected from such an increase in filling volume. The Abrams factors used here for analysis of bladder outlet obstruction (BOOI) and detrusor contractility (BCI) have the advantage of being simple but the disadvantage of not being validated or representing any standardized form of data analysis outside the nomograms from which they are derived. These factors show statistically significant changes after tolterodine, which then are interpreted as
2312
LETTERS TO THE EDITOR
being difficult to explain or postulated to be clinically irrelevant. It may be interesting to look at the details. Apparently 3 different systems for the classification of BOOI are used in the article. Patients are “diagnosed with mild, moderate or severe urinary obstruction (BOOI . . . 20 or greater).”1 These obstruction categories are not explained in the article or in the cited reference.1 Subsequently, the authors state that “BOOI was used . . . and men were classified as obstructed . . . , equivocally obstructed . . . or unobstructed . . . .” This classification would be in agreement with the standardized categories of the provisional International Continence Society (ICS) nomogram. Finally, in table 2 in the article these classifications are mixed up, yielding unobstructed, equivocal, moderate and severe categories. The details of the distribution of patients in such obstruction categories show that, according to ICS standards, only 54% and 57% enrolled in the placebo and tolterodine groups, respectively, were obstructed, and a number were clearly unobstructed. These findings are in agreement with the mean obstruction value, indicating minimal obstruction close to the borderline of equivocally obstructed. The original meaning of “equivocal” is that these cases may be obstructed or may be unobstructed, and it remains unclear how or why they are recategorized here. The use of a simple number such as BOOI outside the limits (20 and 40) of the provisional ICS nomogram is doubtful. Thus, particularly when the interpretation of a decrease in BOOI as a reduction in bladder outlet resistance is difficult to understand, it is essential to take a closer look at the underlying concept. It is generally accepted that bladder outflow conditions can be represented by a line in a pressure/ flow diagram, ie the urethral resistance relation. Bladder outlet obstruction is such a line but with a fixed slope irrespective of the actual urodynamic data and pressure level. It is known that different types of obstruction exist, compressive and constrictive, distinguished by different slopes, and also that in prostatic obstruction the slope is related to the pressure level, ie becomes more constrictive with the degree of obstruction. Thus, before any conclusions are drawn using a simple nonvalidated parameter such as BOOI it should be carefully investigated as to whether the original urodynamic data allow the application of such a simplified analysis. This stipulation is of particular importance when in addition detrusor contractility changes significantly, because Qmax and pdetQmax are the result of outflow resistance and detrusor contractility. If the obstruction type is predominantly constrictive, the observed changes in Qmax and pdetQmax may be mainly due to a decrease in contractility. The BCI factor is derived from the Schaefer nomogram, and is similar to detrusor coefficient. A mean decrease in BCI of approximately 6% is found for tolterodine and reported as a statistically significant difference in detrusor contractility. However, I do not believe we can ignore the increase in bladder filling volume in this same group when quantifying contractility. It is well known that the maximum flow rate increases with bladder filling volume because of an increase in contractility with volume. As for any other muscle working within its physiological range, it is true for the detrusor that the potential muscle power and work increase with the prestretched length. This finding is reflected in the various flow nomograms relating Qmax to the bladder volume, such as the Bristol nomogram, which shows a mean
increase of approximately 12% in the discussed volume range for Qmax. Thus, if changes in bladder contractility are to be quantified, it is necessary to take changes in filling volume into account. In this study a 20% increase in mean bladder filling volume was reported with tolterodine. Such an increase in volume should result in an increase in contractility of approximately 15%, following the usual approximation of contractility being proportional to filling volume to the two thirds, ie V(2/3). Therefore, the reported decrease in mean BCI of 6% despite an expected increase in contractility of 15% actually represents a reduction in detrusor strength of approximately 20%. The authors make the judgment that a 6% decrease in contractility is clinically irrelevant. I think that the actual 20% loss in detrusor contractility with tolterodine is alarming and suggests a much longer observation period, particularly in obstructed men. It leads to an increase in post-void residual volume, and may explain why 3 subjects discontinued the drug because of high PVR or voiding difficulties and the sensation of incomplete emptying. We have to keep in mind that, contrary to the title, only a little more than half of the enrolled men were urodynamically obstructed, and men with large residual volume (more than 108 ml on average) were excluded. To summarize, the urodynamic data are incorrectly analyzed, the potential benefit of volume increases “favor[ing] tolterodine over placebo” is, in fact, much smaller and possibly irrelevant if the increase in post-void residual volume is taken into account, and because of the incorrect interpretation of the data the actual decrease in detrusor contractility associated with administration of the drug is much larger than reported. Respectfully, Werner Schaefer Department of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 1.
Abrams, P.: Bladder outlet obstruction index, bladder contractility index and bladder voiding efficiency: three simple indices to define bladder voiding function. BJU Int, 84: 14, 1999
Reply by Authors. With respect to efficacy, the aim of this study was to give information on safety, and, therefore, the study was not powered to supply data on efficacy. Subset analysis of other tolterodine studies has demonstrated efficacy in male patients. The comments on the indices used to describe BOOI and BCI highlight the fact that there are areas of debate in these measurements. The study protocol stated that only patients with BOOI should be included. It also followed ICS recommendations that urodynamic traces be reviewed centrally. At that review 14% of men were recategorized as having no element of obstruction (BOOI less than 20) but were not excluded from the study. No recommendation has been made concerning patients with BOOI 20 to 40, and it remains conjectural as to whether they should continue to be described as equivocally or mildly obstructed. The true cut point between obstruction and no obstruction is unlikely ever to be defined, since it would require a surgical trial of mammoth proportions.
LETTERS TO THE EDITOR The comment by Schaefer regarding detrusor contractility also reflects an area of ongoing discussion. Indeed, the formula for BCI has recently been questioned as a result of the work at Newcastle and our department. These findings suggest that the lines on the Schaefer nomogram may need to be altered significantly. Schaefer makes the point that the indices used are simple, and this is certainly true. It is also true that more complex mathematical analyses of urodynamic data have not been shown to predict patient outcome better than, for example, BOOI. In terms of patient care, as the article indicates, care must be taken in treating all patients, and increasing data will either increase our confidence in prescribing antimuscarinics in men with OAB, or vice versa.
Re: The Anatomy and Embryology of Posterior Urethral Valves
III,7 congenital stricture8 and Moormann’s ring9) the occlusion is the remnant of the urogenital membrane, and the more proximal COPUM is persistence of the hymen-like tissue due to lack of apoptosis, as Watson had alluded in the 1920s.10 Some would argue that complete understanding of the anatomy and embryology of urethral obstruction in male infants is unimportant, because it does not impact the clinical treatment of the patient. Fortunately, Krishnan et al have helped advance our academic knowledge and the fact that the obstruction can be significantly altered by passage of a catheter alone, which obviously can allow us to modify our management. Respectfully, Paddy Dewan Department of Surgery Sunshine Hospital Victoria, Australia 1.
A. Krishnan, A. de Souza, R. Konijeti and L. S. Baskin J Urol, 175: 1214 –1220, 2006 To the Editor. I am indebted to the thorough work of Krishnan et al, which has added weight to the contention that the term congenital obstructive posterior urethral membrane (COPUM) is appropriate for obstructive lesions in the male posterior urethra. This excellent study will hopefully further the debate, and promote more of the scientific approach applied by the University of California group. However, to be fair to some of our forefathers, while my obsessive recording of all endoscopies has allowed for greater clarification of the concept, and given rise to the term COPUM, Parkkulainen should also be credited for his contribution.1 I think he understood the membrane concept, and was the first urologist to focus our attention. Wigglesworth,2 and Robertson and Hayes3 also provided evidence of membranous obstruction of the posterior urethra but were not urologists and did not debate the urological treatment implications. Interestingly, one of the early descriptions was “like the iris of an eye” in 1856.4 Krishnan et al discuss the variable expression of the degree of obstruction of the lumen, which we have published. However, we have also recognized the variable radiological changes with a similarly obstructing appearance on cystoscopy, indicating that the bladder may respond aggressively in some patients and not in others, although there may also be a ballooning of the membrane distally that increases the obstruction to the flow of urine. There may also be different diseases, one with the urethral anomaly and poor kidneys, and one with good kidneys and severe obstruction. Obviously, we have much to learn about the obstructed infant male urethra and associated findings, and Krishnan et al have stimulated us to do further research. The embryology is the most difficult to research. However, at present I would suggest that we continue to include Cobb’s collar5 (the bulbar urethral narrowing) in the same discussion as the COPUM. However, I would suggest that Cobb’s collar is present in 70% of boys, and is the distal end of the external sphincter in most.6 In those with a fibrous anomaly in the bulbar urethra (also known as Young type
2313
2.
3. 4. 5. 6. 7. 8.
9.
10.
Parkkulainen, K. V.: Posterior urethral obstruction: valvular or diaphragmatic? Endoscopic diagnosis and treatment. In: Birth Defects: Urinary System Malformations in Children. Edited by D. Bergsma and J. W. Duckett. New York: Alan J. Liss, Inc., pp. 63–74, 1977 Wigglesworth, J. S.: The kidneys and urinary tract: urinary bladder and urethra. In: Major Problems in Pathology. Philadelphia: W. B. Saunders Co., vol. 15, pp. 364 –370, 1984 Robertson, W. B. and Hayes, J. A.: Congenital diaphragmatic obstruction of the male urethra. Br J Urol, 41: 592, 1969 Jarjavay, J. F.: Recherches anatomiques sur l’uréthre de l’homme. Paris, 1856 Cobb, B. G., Wolf, J. A. and Ansell, J. S.: Congenital stricture of the proximal urethral bulb. J Urol, 99: 629, 1968 Dewan, P. A., Goh, D. G. and Crameri, J.: Cobb’s collar. Pediatr Surg Int, 10: 243, 1995 Young, H. H., Frontz, W. A. and Baldwin, J. C.: Congenital obstruction of the posterior urethra. J Urol, 3: 289, 1919 Currarino, G. and Stephens, F. D.: An uncommon type of bulbar urethral stricture, sometimes familial, of unknown cause: congenital versus acquired. J Urol, 126: 658, 1981 Moormann, J. G.: Congenital bulbar urethral stenosis as a cause of disease of the urogenital junction. Urologe A, 11: 157, 1972 Watson, E. M.: The structural basis for congenital valve formation in the posterior urethra. J Urol, 7: 371, 1921
Reply by Authors. Congratulations to Dewan for drawing appropriate and well deserved attention to previous posterior urethra scientific investigators. We also appreciate his comments and agree that academic endeavors may have clinical implications. As Dewan indicates, urethral obstruction (ie COPUM) is a spectrum. We continue to see patients with COPUM who have been treated initially with a 5Fr or 8Fr feeding tube as a form of indwelling urethral drainage. Endoscopic treatment may be delayed secondary to prematurity or pulmonary instability. When it is safe to proceed with operation we have often found the COPUM to be “ablated,” with the classic 12 o’clock leaflet of posterior urethral valve nonexistent and the leaflets at 5 o’clock and 7 o’clock nonobstructing. With respect to embryology we agree that a unified explanation remains an enigma. In our careful anatomical analysis of multiple fetal human urethral specimens we have not found any evidence of Cobb’s
2.
3.
Antiphon, P., Elard, S., Benyoussef, A., Fofana, M., Yiou, R., Gettman, M. et al: Laparoscopic promontory sacral colpopexy: is the posterior, recto-vaginal, mesh mandatory? Eur Urol, 45: 655, 2004 Gadonneix, P., Ercoli, A., Salet-Lizee, D., Cotelle, O., Bolner, B., Van Den Akker, M. et al: Laparoscopic sacrocolpopexy with two separate meshes along the anterior and posterior vaginal walls for multicompartment pelvic organ prolapse. J Am Assoc Gynecol Laparosc, 11: 29, 2004 Baessler, K. and Stanton, S. L.: Sacrocolpopexy for vault prolapse and rectocele: do concomitant Burch colposuspension and perineal mesh detachment affect the outcome? Am J Obstet Gynecol, 192: 1067, 2005
2311
Re: Safety and Tolerability of Tolterodine for the Treatment of Overactive Bladder in Men With Bladder Outlet Obstruction P. Abrams, S. Kaplan, H. J. De Koning Gans and R. Millard J Urol, 175: 999 –1004, 2006 To the Editor. This publication contains some errors that I would like to discuss. First, I find it remarkable that in a publication about the “safety and tolerability of tolterodine for the treatment of overactive bladder [OAB]” no new or useful information about the treatment of OAB is found. The data and conclusions are limited to the statement that it is not dangerous to administer tolterodine to men with OAB because it does not adversely affect urinary tract function and these men find it tolerable. But is this convincingly demonstrated? And is there any improvement in OAB, ie is there any benefit? There is no explicit analysis of the drug trial data with respect to improvement of OAB, ie of the bothersome symptoms of urgency, urge incontinence, increased frequency and nocturia. I found urodynamic data indicating that some urodynamically measurable aspects of OAB may not have improved with tolterodine. Such data are volume at first detrusor contraction (which can be taken as an indicator of urgency) and volume at maximum bladder capacity (which can be taken as an indicator of frequency). The potential benefit from the reported increases in volumes for these 2 key OAB symptoms seems lost because of the increase in post-void residual (PVR) volume. It is difficult to see how a patient could benefit from a larger bladder capacity when the voided volume increases little or not at all due to an increase in residual volume. Unfortunately, this aspect is not discussed in the article. I doubt that the statement that these volume increases “favor[ing] tolterodine over placebo” will stand if the PVR increase is properly taken into account. These doubts are confirmed by the decrease in voiding efficiency, which was statistically significant. My second problem with this publication is that I am not convinced that the urodynamic data are properly analyzed and interpreted, either by the concept of testing for equivalence of changes in peak urinary flow rate (Qmax) and detrusor pressure at maximal flow rate (pdetQmax), or by the methodology based on the Abrams factors. I do not think it is meaningful to compare Qmax and pdetQmax as primary end points without taking significant changes and/or differences in bladder filling volume into account. Such volume changes could have been expected and are reported with tolterodine as being significant. An increase in Qmax and, dependent on the type of obstruction, some increase in pdetQmax are to be expected from such an increase in filling volume. The Abrams factors used here for analysis of bladder outlet obstruction (BOOI) and detrusor contractility (BCI) have the advantage of being simple but the disadvantage of not being validated or representing any standardized form of data analysis outside the nomograms from which they are derived. These factors show statistically significant changes after tolterodine, which then are interpreted as
2312
LETTERS TO THE EDITOR
being difficult to explain or postulated to be clinically irrelevant. It may be interesting to look at the details. Apparently 3 different systems for the classification of BOOI are used in the article. Patients are “diagnosed with mild, moderate or severe urinary obstruction (BOOI . . . 20 or greater).”1 These obstruction categories are not explained in the article or in the cited reference.1 Subsequently, the authors state that “BOOI was used . . . and men were classified as obstructed . . . , equivocally obstructed . . . or unobstructed . . . .” This classification would be in agreement with the standardized categories of the provisional International Continence Society (ICS) nomogram. Finally, in table 2 in the article these classifications are mixed up, yielding unobstructed, equivocal, moderate and severe categories. The details of the distribution of patients in such obstruction categories show that, according to ICS standards, only 54% and 57% enrolled in the placebo and tolterodine groups, respectively, were obstructed, and a number were clearly unobstructed. These findings are in agreement with the mean obstruction value, indicating minimal obstruction close to the borderline of equivocally obstructed. The original meaning of “equivocal” is that these cases may be obstructed or may be unobstructed, and it remains unclear how or why they are recategorized here. The use of a simple number such as BOOI outside the limits (20 and 40) of the provisional ICS nomogram is doubtful. Thus, particularly when the interpretation of a decrease in BOOI as a reduction in bladder outlet resistance is difficult to understand, it is essential to take a closer look at the underlying concept. It is generally accepted that bladder outflow conditions can be represented by a line in a pressure/ flow diagram, ie the urethral resistance relation. Bladder outlet obstruction is such a line but with a fixed slope irrespective of the actual urodynamic data and pressure level. It is known that different types of obstruction exist, compressive and constrictive, distinguished by different slopes, and also that in prostatic obstruction the slope is related to the pressure level, ie becomes more constrictive with the degree of obstruction. Thus, before any conclusions are drawn using a simple nonvalidated parameter such as BOOI it should be carefully investigated as to whether the original urodynamic data allow the application of such a simplified analysis. This stipulation is of particular importance when in addition detrusor contractility changes significantly, because Qmax and pdetQmax are the result of outflow resistance and detrusor contractility. If the obstruction type is predominantly constrictive, the observed changes in Qmax and pdetQmax may be mainly due to a decrease in contractility. The BCI factor is derived from the Schaefer nomogram, and is similar to detrusor coefficient. A mean decrease in BCI of approximately 6% is found for tolterodine and reported as a statistically significant difference in detrusor contractility. However, I do not believe we can ignore the increase in bladder filling volume in this same group when quantifying contractility. It is well known that the maximum flow rate increases with bladder filling volume because of an increase in contractility with volume. As for any other muscle working within its physiological range, it is true for the detrusor that the potential muscle power and work increase with the prestretched length. This finding is reflected in the various flow nomograms relating Qmax to the bladder volume, such as the Bristol nomogram, which shows a mean
increase of approximately 12% in the discussed volume range for Qmax. Thus, if changes in bladder contractility are to be quantified, it is necessary to take changes in filling volume into account. In this study a 20% increase in mean bladder filling volume was reported with tolterodine. Such an increase in volume should result in an increase in contractility of approximately 15%, following the usual approximation of contractility being proportional to filling volume to the two thirds, ie V(2/3). Therefore, the reported decrease in mean BCI of 6% despite an expected increase in contractility of 15% actually represents a reduction in detrusor strength of approximately 20%. The authors make the judgment that a 6% decrease in contractility is clinically irrelevant. I think that the actual 20% loss in detrusor contractility with tolterodine is alarming and suggests a much longer observation period, particularly in obstructed men. It leads to an increase in post-void residual volume, and may explain why 3 subjects discontinued the drug because of high PVR or voiding difficulties and the sensation of incomplete emptying. We have to keep in mind that, contrary to the title, only a little more than half of the enrolled men were urodynamically obstructed, and men with large residual volume (more than 108 ml on average) were excluded. To summarize, the urodynamic data are incorrectly analyzed, the potential benefit of volume increases “favor[ing] tolterodine over placebo” is, in fact, much smaller and possibly irrelevant if the increase in post-void residual volume is taken into account, and because of the incorrect interpretation of the data the actual decrease in detrusor contractility associated with administration of the drug is much larger than reported. Respectfully, Werner Schaefer Department of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 1.
Abrams, P.: Bladder outlet obstruction index, bladder contractility index and bladder voiding efficiency: three simple indices to define bladder voiding function. BJU Int, 84: 14, 1999
Reply by Authors. With respect to efficacy, the aim of this study was to give information on safety, and, therefore, the study was not powered to supply data on efficacy. Subset analysis of other tolterodine studies has demonstrated efficacy in male patients. The comments on the indices used to describe BOOI and BCI highlight the fact that there are areas of debate in these measurements. The study protocol stated that only patients with BOOI should be included. It also followed ICS recommendations that urodynamic traces be reviewed centrally. At that review 14% of men were recategorized as having no element of obstruction (BOOI less than 20) but were not excluded from the study. No recommendation has been made concerning patients with BOOI 20 to 40, and it remains conjectural as to whether they should continue to be described as equivocally or mildly obstructed. The true cut point between obstruction and no obstruction is unlikely ever to be defined, since it would require a surgical trial of mammoth proportions.
LETTERS TO THE EDITOR The comment by Schaefer regarding detrusor contractility also reflects an area of ongoing discussion. Indeed, the formula for BCI has recently been questioned as a result of the work at Newcastle and our department. These findings suggest that the lines on the Schaefer nomogram may need to be altered significantly. Schaefer makes the point that the indices used are simple, and this is certainly true. It is also true that more complex mathematical analyses of urodynamic data have not been shown to predict patient outcome better than, for example, BOOI. In terms of patient care, as the article indicates, care must be taken in treating all patients, and increasing data will either increase our confidence in prescribing antimuscarinics in men with OAB, or vice versa.
Re: The Anatomy and Embryology of Posterior Urethral Valves
III,7 congenital stricture8 and Moormann’s ring9) the occlusion is the remnant of the urogenital membrane, and the more proximal COPUM is persistence of the hymen-like tissue due to lack of apoptosis, as Watson had alluded in the 1920s.10 Some would argue that complete understanding of the anatomy and embryology of urethral obstruction in male infants is unimportant, because it does not impact the clinical treatment of the patient. Fortunately, Krishnan et al have helped advance our academic knowledge and the fact that the obstruction can be significantly altered by passage of a catheter alone, which obviously can allow us to modify our management. Respectfully, Paddy Dewan Department of Surgery Sunshine Hospital Victoria, Australia 1.
A. Krishnan, A. de Souza, R. Konijeti and L. S. Baskin J Urol, 175: 1214 –1220, 2006 To the Editor. I am indebted to the thorough work of Krishnan et al, which has added weight to the contention that the term congenital obstructive posterior urethral membrane (COPUM) is appropriate for obstructive lesions in the male posterior urethra. This excellent study will hopefully further the debate, and promote more of the scientific approach applied by the University of California group. However, to be fair to some of our forefathers, while my obsessive recording of all endoscopies has allowed for greater clarification of the concept, and given rise to the term COPUM, Parkkulainen should also be credited for his contribution.1 I think he understood the membrane concept, and was the first urologist to focus our attention. Wigglesworth,2 and Robertson and Hayes3 also provided evidence of membranous obstruction of the posterior urethra but were not urologists and did not debate the urological treatment implications. Interestingly, one of the early descriptions was “like the iris of an eye” in 1856.4 Krishnan et al discuss the variable expression of the degree of obstruction of the lumen, which we have published. However, we have also recognized the variable radiological changes with a similarly obstructing appearance on cystoscopy, indicating that the bladder may respond aggressively in some patients and not in others, although there may also be a ballooning of the membrane distally that increases the obstruction to the flow of urine. There may also be different diseases, one with the urethral anomaly and poor kidneys, and one with good kidneys and severe obstruction. Obviously, we have much to learn about the obstructed infant male urethra and associated findings, and Krishnan et al have stimulated us to do further research. The embryology is the most difficult to research. However, at present I would suggest that we continue to include Cobb’s collar5 (the bulbar urethral narrowing) in the same discussion as the COPUM. However, I would suggest that Cobb’s collar is present in 70% of boys, and is the distal end of the external sphincter in most.6 In those with a fibrous anomaly in the bulbar urethra (also known as Young type
2313
2.
3. 4. 5. 6. 7. 8.
9.
10.
Parkkulainen, K. V.: Posterior urethral obstruction: valvular or diaphragmatic? Endoscopic diagnosis and treatment. In: Birth Defects: Urinary System Malformations in Children. Edited by D. Bergsma and J. W. Duckett. New York: Alan J. Liss, Inc., pp. 63–74, 1977 Wigglesworth, J. S.: The kidneys and urinary tract: urinary bladder and urethra. In: Major Problems in Pathology. Philadelphia: W. B. Saunders Co., vol. 15, pp. 364 –370, 1984 Robertson, W. B. and Hayes, J. A.: Congenital diaphragmatic obstruction of the male urethra. Br J Urol, 41: 592, 1969 Jarjavay, J. F.: Recherches anatomiques sur l’uréthre de l’homme. Paris, 1856 Cobb, B. G., Wolf, J. A. and Ansell, J. S.: Congenital stricture of the proximal urethral bulb. J Urol, 99: 629, 1968 Dewan, P. A., Goh, D. G. and Crameri, J.: Cobb’s collar. Pediatr Surg Int, 10: 243, 1995 Young, H. H., Frontz, W. A. and Baldwin, J. C.: Congenital obstruction of the posterior urethra. J Urol, 3: 289, 1919 Currarino, G. and Stephens, F. D.: An uncommon type of bulbar urethral stricture, sometimes familial, of unknown cause: congenital versus acquired. J Urol, 126: 658, 1981 Moormann, J. G.: Congenital bulbar urethral stenosis as a cause of disease of the urogenital junction. Urologe A, 11: 157, 1972 Watson, E. M.: The structural basis for congenital valve formation in the posterior urethra. J Urol, 7: 371, 1921
Reply by Authors. Congratulations to Dewan for drawing appropriate and well deserved attention to previous posterior urethra scientific investigators. We also appreciate his comments and agree that academic endeavors may have clinical implications. As Dewan indicates, urethral obstruction (ie COPUM) is a spectrum. We continue to see patients with COPUM who have been treated initially with a 5Fr or 8Fr feeding tube as a form of indwelling urethral drainage. Endoscopic treatment may be delayed secondary to prematurity or pulmonary instability. When it is safe to proceed with operation we have often found the COPUM to be “ablated,” with the classic 12 o’clock leaflet of posterior urethral valve nonexistent and the leaflets at 5 o’clock and 7 o’clock nonobstructing. With respect to embryology we agree that a unified explanation remains an enigma. In our careful anatomical analysis of multiple fetal human urethral specimens we have not found any evidence of Cobb’s