UIJ Urotoday International Journal® Table of Contents: August, 2013

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UIJ UroToday International Journal® Table of Contents: August, 2013

Benign Prostatic Hyperplasia • Predictors of Unsuccessful Trials without Catheters in Acute Urinary Retention Secondary to Benign Prostatic Hyperplasia Bijit Lodh, Somarendra Khumukcham, Sandeep Gupta, Kaku Akoijam Singh, Rajendra Singh Sinam

Overactive Bladder • Management of Overactive Bladder (OAB) in Elderly Men and Women with Combined, High-Dosed Antimuscarinics without Increased Side Effects Kirill Kosilov, Sergey Loparev, Marina Ivanovskaya, Lily Kosilova

Prostate Cancer • Prevalance of Prostate Carcinoma in the Indian Population: The Need to Revise Serum Prostate Specific Antigen (PSA) Nandan R. Pujari

Renal Cell Carcinoma • Common Laboratory Values Are Unreliable in Identifying the Presence of Metastatic Renal Cell Carcinoma in the Liver and Bones Joshua E. Logan, David A. Staneck, Mary H. James, Jack W. Lambert, Robert W. Given, Raymond S. Lance, Michael D. Fabrizio, Stephen B. Riggs

Stones Disease • Analysis of the Feasibility and Efficacy of Ambulatory/Day Care Percutaneous Nephrolithotomy: An Initial Experience Adittya K. Sharma, M. Nagabhushan, G. N. Girish, A. J. Kamath, C. S. Ratkal, G. K. Venkatesh

Trauma and Reconstruction • The Challenge of Difficult Catheterization in Men: A Novel Technique and Review of the Literature Mario Gardi, Giulio Massimo Balta, Marcello Repele, Nicola Zanovello, Giovanni Betto, Simonetta Fracalanza, Wanni Battanello, Bruno Santoni, Silvia Secco, Andrea Agostini, Massimo Dal Bianco

• The Use of Tamsulosin in Voiding Cystourethrograms for Pelvic Floor Urethral Distraction Injuries Nandan R. Pujari, Sanjay B. Kulkarni

Letter to the Editor • Commentary on “Parental Attitudes Toward Fertility Preservation in Boys with Cancer: Context of Different Risk Levels of Infertility and Success Rates of Fertility Restoration,” Sadri-Ardekani et al. (2013). Fertil Steril 99: 796-802

©2013 Digital Science Press, Inc. / UIJ / Vol 6 / Iss 4 / August http://www.urotodayinternationaljournal.com ISSN 1944-5792 (print), ISSN 1944-5784 (online) Thomas W. McLean, Hooman Sadri-Ardekani, Anthony Atala

Case Reports • Giant Leiomyoma of the Ureter Leading to a Loss of Renal Function: A Case Report Mohamad Sajid Bazaz, Tanveer Iqbal Dar, Nuzhat Tabasum, Mohammad Saleem Wani, Abdul Rouf Khawaja

• Isolated Ano-vaginal Fistulae without Associated Vesicovaginal Fistulae Following Prolonged Labor: A Rare Entity Vishwajeet Singh, Dheeraj Kumar Gupta, Rahul Janak Sinha

• Squamous Cell Carcinoma Arising in Keratinizing Desquamative Squamous Metaplasia (KDSM) of the Renal Pelvis Mohammed S. Al-Marhoon, P. A. M. Saparamadu, Krishna P. Venkiteswaran, Omar Shareef, Joseph Mathewkunju

• Successful En-Bloc Kidney Transplantation from a 7-Month-Old Donor Weighing 14.3 Pounds Into an Adult Recipient: A Case Report Taqi F. Toufeeq Khan, Suhaib Kamal, Basem Koshaji, Faheem Akhtar

©2013 Digital Science Press, Inc. / UIJ / Vol 6 / Iss 4 / August http://www.urotodayinternationaljournal.com ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Predictors of Unsuccessful Trials without Catheters in Acute Urinary Retention Secondary to Benign Prostatic Hyperplasia

Bijit Lodh, Somarendra Khumukcham, Sandeep Gupta, Kaku Akoijam Singh, Rajendra Singh Sinam Submitted May 4, 2013 - Accepted for Publication June 14, 2013

Abstract

Introduction: Acute urinary retention (AUR) is the most important event in the natural history of benign prostatic hyperplasia (BPH) that calls for urinary catheterization. Trial without catheter (TWOC) is an ambulatory care protocol, failure of which requires re-catheterization, a follow-up visit, subsequent evaluation, and surgical intervention. The aim of the study was to identify independent predictors of unsuccessful TWOC. Methods: The present study enrolled 83 patients with a first episode of AUR secondary to BPH. We have recorded details of various factors, including age, international prostate symptom score (IPSS), total prostate volume (TPV), transition zone volume (TZV), transition zone index (TZI), intravesical prostatic protrusion (IPP), and residual urine volume (RUV) drained following catheterization. Administration of 0.4 mg of tamsulosin once a day for 7 days was given to all following catheterization and TWOC performed on the eighth day. Our definition of unsuccessful trial was the inability to pass urine or post-void residual urine > 150 mL on ultrasound, with a maximum flow rate < 10 mL/sec. Statistical Package for the Social Sciences (SPSS) 16.0 was used for statistical analysis. Multivariate analysis was performed to identify independent predictors. Independent t-test and Fisher’s exact tests were used for other statistical analysis where a P value of < 0.05 was considered significant. Receiver operating characteristic curves (ROC) were constructed using cutoff values for independent predictors. Results: TWOC was unsuccessful in 48 (57.83%) patients. Multivariate analyses revealed that age (odds ratio = 1.069; 95% CI = 1.002-1.140; P value = 0.042), TZV (odds ratio = 1.662; 95% CI = 1.035-2.670; P value = 0.035), TZI (odds ratio = 0.00; 95% CI = 0.00-0.150; P value = 0.032), and RUV (1.003, 1.000-1.007, 0.38) are independent predictors of a failed trial. The failure rates of the voiding trial based on grades I to III IPP were 2.08% (1 of 48 cases), 10.41% (5 of 48), and 18.75% (9 of 48). Conclusion: Our data suggested that age, IPP, TZV, TZI, and RUV are significant risk factors for unsuccessful TWOC. Evaluation of a first episode of AUR secondary to BPH in respect to the previously mentioned factors may guide urologists during subsequent evaluation and treatment without giving a failed trial.

Introduction reduce the risk of perioperative morbidity and mortality as well as to allow the bladder to recover its contractility. Trial Benign prostatic hyperplasia (BPH) is commonly associated with without catheter (TWOC) is a novel approach, and it should be spontaneous acute urinary retention (AUR) and is regarded as a considered for those with spontaneous AUR, with a success rate sign of disease progression [1-3]. Management of this condition of 23 to 40% [4,5]. A successful trial not only delays surgery, but must begin with identifying risk factors for developing AUR, may also avoid it. Nevertheless, incidence of an unsuccessful regular follow-up, and surgical intervention for those who trial is high for re-catheterization. Failed trials could be avoided might benefit. Surgery should be delayed when possible to by identifying significant, independent risk factors. We should

KEYWORDS: Acute urinary retention, benign prostatic hyperplasia, trial without catheter, intravesical prostatic protrusion, transition zone index CORRESPONDENCE: Bijit Lodh, MS (General Surgery), MCh (Trainee in Urology), Regional Institute of Medical Sciences, Imphal, Manipur, India ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 43. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.02

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.02 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study selectively consider those patients who are at a high risk of Figure 1. TRUS for volumetric measurement of the failure and counsel them for further management to extend prostate. elective surgery, without considering an unnecessary catheter- free trial. The aim of our study was to evaluate independent risk factors of unsuccessful trials.

Methods

Study Design

This was a prospective study conducted at our urology department from January 2012 to March 2013. Ethical approval was obtained from the Research and Ethics Committee of the institute.

Inclusion and Exclusion Criteria

Eighty-three male patients 45 years or above who presented to the urology clinic with a first episode of AUR secondary to BPH were included in this study. Informed written consent was taken from the participants. Exclusion criteria included patients receiving medical treatment for BPH and overactive bladder, the presence of gross hematuria/urinary tract infection/chronic constipation, known or suspected carcinoma of the prostate Figure 2. Grade III IPP on mid-sagittal view of TRUS. on digital rectal examination (DRE)/transrectal ultrasound (TRUS), the presence of stricture urethra/vesical calculus, failed catheterization, bed-ridden/ severely comorbid patients, a history of recent anesthesia/surgery, and neurological disorders affecting continence.

Data Collection and Statistical Analysis

All the eligible patients were initially managed with peri- urethral catheters (PUC), and the residual urine volume (RUV) drained with the catheter was recorded. Details of the various parameters, including age, international prostate symptom score (IPSS), total prostate volume (TPV), transition zone volume (TZV), transition zone index (TZI), and intravesical prostatic protrusion (IPP) were also recorded. The transition zone index is the ratio of the transition zone to total prostate volume. TRUS was used for volumetric measurements of the prostate (Figure 1) using the ellipsoid formula keyed into the ultrasound machine (SonoAce X6, Medison). Intravesical prostatic protrusion was measured by calculating the vertical distance from the protruded tip to the circumference of the bladder at the prostate base taken at the mid-sagittal view (Figure 2). Intravesical prostatic protrusion was graded I to III according to the classification system used by Nose et al. [6]. performed using SPSS 16.0. An independent t-test was used to Administration of 0.4 mg of tamsulosin once a day for 7 days determine the statistically significant difference between the was given to all following catheterization and TWOC performed means in 2 groups (successful and unsuccessful). Multivariate on the 8th day. We have defined an unsuccessful trial as the analysis was performed to identify which were independent inability to pass urine or post-void residual urine > 150 mL on predictors of an unsuccessful trial. A Fisher’s exact test was used ultrasound with a maximum flow rate < 10 mL/sec, similar to to determine significant differences between grades of IPP in what’s described by Osman et al. [7]. Statistical analysis was respect to TWOC outcomes. Receiver operating characteristic

` Table 1. Parameters with their respective means. Parameter (Mean Value) Successful TWOC Unsuccessful TWOC P Value N = 35 N = 48 Age 62.77 ± 10.18 (46-85) 71.79 ± 6.98 (57-87) 0.047 PSA 5.39 ± 4.06 (0.50-16.23) 6.03 ± 5.37 (0.78-24.19) 0.072 TPV 48 ± 15.66 (30.09-89.51) 57.36 ± 19.15 (28.76-102.31) 0.196 TZV 17.79 ± 7.1 (5.42-36.93) 25.44 ± 12.6 (2.69-56.5) 0.003 TZI 0.36 ± 0.06 (0.17-0.45) 0.42 ± 0.13 (0.10-0.66) 0.002 IPSS 21.97 ± 8.69 (7-35) 22.62 ± 7.31 (11-35) 0.223 RUV 499.7 ± 137.7 (197.66-721.36 652.73 ± 225.81 (124.6-1067.07) 0.008 TWOC: trial without catheter; N: number; PSA: prostate specific antigen; TPV: total prostate volume; TZV: transition zone volume; TZI: transition zone index; IPSS: international prostate symptom scores; RUV: residual urine volume drained with catheter.

Table 2. Multivariate analysis showing independent risk factors. 95% CI for Exp (B) B SE Wald df Sig Exp (B) Lower Upper Step 1a Age 0.67 0.033 4.135 1 0.042 1.069 1.002 1.140 PSA -0.039 0.053 0.536 1 0.464 0.962 0.867 1.140 TPV -0.184 0.099 3.455 1 0.063 0.832 0.685 1.010 TZV 0.508 0.242 4.425 1 0.035 1.662 1.035 2.670 TZI -22.177 10.348 4.593 1 0.032 0.00 0.00 0.150 IPSS -0.021 0.034 0.388 1 0.534 0.979 0.915 1.047 RUV 0.003 0.002 4.306 1 0.038 1.003 1 1.007 constant 2.175 4.527 0.231 1 0.631 8.798 - - SA: prostate specific antigen; TPV: total prostate volume; TZV: transition zone volume; TZI: transition zone index; IPSS: international prostate symptom scores; RUV: residual urine volume drained with catheter; Exp (B): odds ratio

(ROC) curves were constructed using cutoff values for different 2, which revealed age (odds ratio = 1. 069; 95% CI = 1.002- significant predictors. A P value of < 0.05 was considered 1.140; P value = 0. 042), TZV (odds ratio = 1.662; 95% CI = statistically significant. 1.035-2.670; P value = 0. 035), TZI (odds ratio = 0. 00; 95% CI = 0. 00-0.150; P value = 0. 032), and RUV (1.003, 1.000-1.007, Results 0.38) as independent risk factors. Table 3 compares the grades of IPP in respect to TWOC outcome, and it shows grade III An unsuccessful trial was observed in 48 (57.83%) patients. Table intravesical prostatic protrusion is an important risk factor. The 1 shows the parameters with their respective means. The mean area under receiver operating characteristics (AUROC) curve for age (71.79 ± 6.98) of the TWOC failure group was significantly independent predictors, including age, TZV, TZI, and RUV, were higher than the successful group, with a P value of 0.047. Mean 0.771, 0.695, 0.737, and 0.736, respectively (Figure 3). A cutoff values of TZV, TZI, and RUV were significantly different in both value of 69 for age detected TWOC failure with sensitivity and groups, with a P value of 0.003, 0.002, and 0.008, respectively. specificity of 66.70% and 80.10%, respectively (Figure 4).A Significant association (P = 0.001) was observed between the cutoff value of 22.88 mL for TZV showed sensitivity (54.20%) IPP and TWOC outcome. Multivariate analysis is shown in Table and specificity (77.10%) for the prediction of unsuccessful

Table 3. Grades of IPP with respect to TWOC outcome. Figure 4. Receiver operating characteristics (ROC) curve constructed using cutoff values for age. Grades of Successful Unsuccessful P Value IPP (mm) TWOC TWOC N = 35 N = 48 grade I 11 (31.43%) 1 (2.08%) P = 0.001 grade II 3 (8.57%) 5 (10.41%) grade III 0 9 (18.75%) grade I versus grade II: P = 0.018 grade II versus grade III: P = 0.082 grade I versus grade III: P = 0.001

grade I (< 5 mm); grade II (5-10 mm); grade III (> 10 mm) IPP: intravesical prostate protrusion; TWOC: trial without catheter; N: number

Figure 3. Area under receiver operating characteristics (AUROC) curve for independent predictors.

Figure 5. ROC curve constructed using cutoff values for TZV.

TWOC (Figure 5). Similarly, a cutoff value of 0.42 and 654 mL showed sensitivity and specificity of 62.50%, 88.60% for TZI (Figure 6), and 58.30%, 88.60% for RUV, respectively (Figure 7).

Discussion

Trial without a catheter has become a standard practice worldwide for men with BPH and AUR. According to the Agency for Health Care Policy and Research guidelines one of

Figure 6. ROC curve constructed using cutoff values for Figure 7. ROC curve constructed using cutoff values TZI. for residual urine volume (RUV) drained at first catheterization.

cutoff value of 0.42 and 654 mL, respectively. Similarly, age and the absolute indications for primary surgical management of TPV were also significant predictors, with a specificity of 80.10% BPH is refractory urinary retention/unsuccessful catheter trial and 77.10% for a cutoff value of 69 and 22.88 mL, respectively. [8]. From the viewpoint of the patient, refractory retention Analyzing AUROC for different risk factors, we found that age is usually a feared situation, with increasing agony, a visit to has a maximum area (Figure 3), meaning it can predict the the emergency room, re-catheterization, follow-up visits, an outcome better. Although prostate volume was considered one attempt at catheter removal, and eventual recovery or surgery. of the predictors of an unsuccessful trial, we have observed that Overall it is an uncomfortable and time-consuming process. In it is the TZV and TZI that predicts the outcome, not the TPV. this study we evaluated the significant risk factors that could International prostate symptom score (IPSS) did not predict predict the outcome of TWOC, especially in respect to failure. the outcome in our study as opposed to what was observed by The presence of significant predictors of an unsuccessful trial Bhomi et al. [12]. PSA did not predict the outcome in our study, in patients with a first episode of AUR secondary to BPH can which is in ordinance with the findings of Zeif et al. [13]. In the avoid re-catheterization-related discomfort and agony with Reten-World survey by Emberton et al. [14], age (> 65 years) and selective consideration for elective surgery. In this study we RUV (> 1L) drained at catheterization were found to have a high found that IPP, TZI, TZV, RUV, and age are independent risk probability of unsuccessful trial, but the present study showed factors for unsuccessful trials. Intraprostatic protrusion was a higher cutoff value for age (69 years) and a lower cutoff value found to be one of the significant predictors, which was for RUV (654 mL). According to Shanmugasundaram et al. [10], consistent with the observations of Osman et al. [7], Tan et al. residual urine > 500 mL, gland size > 50 mL, and age older than [9], Shanmugasundaram et al. [10], and Paramananthan et al. 65 years are associated with failed trial. Cystometrography [11]. (CMG) is a more invasive procedure and not recommended for routine evaluation of BPH patients [15]. The most important Comparing grades of IPP, a significant difference was noticed in indication of urodynamic studies in patients with BPH is those grade I and III (P = 0.001) but not in grade II and III (P = 0.082), having chronic urinary retention (CUR) because detrusor under as shown in Table 3. Transition zone index and RUV were found activity (DUA) is seen in low-pressure chronic retention (LPCR). to be significant predictors, with high specificity (88.60%) for a As our inclusion criterion was patients with a first episode of

AUR, we have not evaluated the effect of CMG parameters to 4. Fitzpatrick, J. M. and R. S. Kirby (2006). "Management predict the outcome of TWOC. of acute urinary retention." BJU Int 97 Suppl 2: 16-20; discussion 21-12. PubMed | CrossRef Observational studies have suggested alpha-blockers significantly improve the outcome of TWOC, with success 5. Kaplan, S. A., A. J. Wein, et al. (2008). "Urinary retention rates between 48 to 62% [16-20]. Patients receiving 5-alpha and post-void residual urine in men: separating truth from reductase inhibitors may have impact on TWOC outcome. tradition." J Urol 180(1): 47-54. PubMed | CrossRef Reynard et al. [21] have demonstrated that anticholinergics used in BPH patients leads to a small increase in post-void 6. Nose, H., K. T. Foo, et al. (2005). "Accuracy of two residual (PVR) without significantly increasing the risk of AUR. noninvasive methods of diagnosing bladder outlet Considering this, patients receiving alpha-blockers, 5-alpha obstruction using ultrasonography: intravesical prostatic reductase inhibitors, and anticholinergics were excluded from protrusion and velocity-flow video urodynamics." Urology the study. The duration of catheterization before TWOC alters 65(3): 493-497. PubMed | CrossRef the chance of a successful trial of catheter removal [4,14,22]. In one study, a successful TWOC was achieved in 44% of patients 7. Osman, S. S., M. Z. Zainuddin, et al. (2013). "Predicting after the first day of catheterization, in 51% of patients after outcome of trial of voiding without catheter in acute the second day, and in 62% of patients after 7 days. [23] In urinary retention with Intravesical Prostatic Protrusion." this study, we considered TWOC on the eighth day. Clean Malays J Med Sci 20(1): 56-59. intermittent self-catheterization (CISC) is a safe, simple, and well-accepted technique that may also increase the rate of 8. McConnell, J. D., M. J. Barry, et al. (1994). "Benign prostatic successful spontaneous voiding. A period of CISC prior to TURP hyperplasia: diagnosis and treatment. Agency for Health may be useful in patients with LPCR, as it may allow recovery of Care Policy and Research." Clin Pract Guidel Quick Ref bladder contractility. A urethral catheter within the bladder has Guide Clin(8): 1-17. PubMed been found to result in bacterial colonization of the bladder at a rate of 4% a day, an important factor accounting for a 9. Tan, Y. H. and K. T. Foo (2003). "Intravesical prostatic significant increased morbidity from infection. However, in this protrusion predicts the outcome of a trial without catheter study peri-urethral bleeding was noticed in 3 patients following following acute urine retention." J Urol 170(6 Pt 1): 2339- catheterization, and no patient developed a febrile UTI. 2341. PubMed | CrossRef

Conclusion 10. 10. Shanmugasundaram R and Nitin SK. Is there a better indicator for predicting the outcome of trial without An unnecessary trial of catheter removal should be avoided catheter? Indian J Urol Oct-Dec 2007; 23(4): 485–486. in patients with acute urinary retention secondary to BPH. 11. Paramananthan, M., J. G. B. David, et al. (2007). "Intravesical Unsuccessful trial not only lengthens the overall process but Prostatic Protrusion is Better Than Prostate Volume in also possess discomfort from the patient’s standpoint. Our Predicting the Outcome of Trial Without Catheter in data suggests that age, TZV, TZI, RUV, and IPP are important White Men Presenting With Acute Urinary Retention: A independent predictors of unsuccessful TWOC. Identifications Prospective Clinical Study." J Urol 178(2): 573-577. of values higher than or equal to the cutoff for specific independent risk factors can substantially predict the failure 12. Bhomi, K. K. and C. L. Bhattachan (2011). "Factors predicting of TWOC. Therefore, we would recommend not performing the success of a trial without catheter in acute urinary TWOC once these risk factors are identified. retention secondary to benign prostatic hyperplasia." REFERENCES Nepal Med Coll J 13(3): 178-181. PubMed 13. Zeif, H. J., D. M. A. Wallace, et al. (2010). "Predictors of 1. Odunayo, K. and J. S. Mark. (2009). "Management of Acute successful trial without catheter in acute urinary retention. and Chronic Retention in Men." Eur Urol Suppl 8: 523-529. Brit J Med Surg Urol 3(1): 5-10. 2. Roehrborn, C. G. (2008). "BPH progression: concept and key 14. Emberton, M. and J. M. Fitzpatrick (2008). "The Reten- learning from MTOPS, ALTESS, COMBAT, and ALF-ONE." World survey of the management of acute urinary BJU Int 101 Suppl 3: 17-21. PubMed | CrossRef retention: preliminary results." BJU Int 101 Suppl 3: 27-32. PubMed | CrossRef 3. Michael, M. (2006). "The MTOPS Study: New Findings, New Insights, and Clinical Implications for the Management of 15. Herbert, L. (2004). "Evaluating Men with Benign Prostatic BPH." Eur Urol Suppl 5: 628-633. Hyperplasia." Rev Urol 6(Suppl 1): S8-S15.

16. Tiong, H. Y., M. J. Tibung, et al. (2009). "Alfuzosin 10 mg once daily increases the chances of successful trial without catheter after acute urinary retention secondary to benign prostate hyperplasia." Urol Int 83(1): 44-48. PubMed | CrossRef

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©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.02 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Management of Overactive Bladder (OAB) in Elderly Men and Women with Combined, High-Dosed Antimuscarinics without Increased Side Effects

Kirill Kosilov, Sergey Loparev, Marina Ivanovskaya, Lily Kosilova Submitted April 16, 2013 - Accepted for Publication July 14, 2013 Abstract

Objectives: Numerous elderly patients with overactive bladder (OAB) demonstrate insufficient treatment results under antimuscarinic monotherapy with dose increase. To reduce the OAB symptoms and to estimate safety and tolerability of non-invasive treatment, we evaluated the use of combined antimuscarinics as the alternatives. Methods: Eighty-one patients older than 65 years, both male and female, who earlier received (for 6 months or more before our study) double-dose antimuscarinic monotherapy (trospium), whose initial symptoms did not resolve (or the improvement was short lived), and who experienced mild or no side effects, were included in this study. The patients demonstrated urodynamic-proven overactive bladder with daily incontinence, increased intravesical pressure, and reduced bladder capacity. Taking into account the strength of the initial study treatment, they were distributed into 3 groups and treated with 2 antimuscarinics. The patients underwent urodynamic examination before enrollment in the sixth week and in the fourth month. During the whole treatment period, they kept special bladder diaries where they, among other issues, described side effects during treatment. Results: Significant changes were noted at the 6-week follow-up in all 3 groups. The average number of daily incontinence events decreased from 6 to 2 events. The average maximum bladder capacity (177 to 356 mL) and

reflex volume (149 to 284 mL) increased; detrusor compliance also improved (average, 16 to 37 mL/cm 2H O). Twenty-four patients reported side effects; 3 of them discontinued the successful treatment due to this reason. Seven other patients did not receive any noticeable improvement of detrusor dysfunction, although they did not report any side effects. Conclusion: The majority of elderly patients, who previously demonstrated unsatisfactory results under dose- escalated monotherapy, were treated successfully with combined high-dosage antimuscarinics (87.6 %). The quantity of side effects was comparable to that of normal-dosed antimuscarinics. Take-Home Message: The majority of elderly patients, who continued to suffer from symptoms of overactive bladder after dose-escalated antimuscarinic monotherapy, showed subjective and objective treatment success. The therapy used the combination of high-dosed antimuscarinics (87.6%). Obtained side effects were comparable to (did not exceed) the single-drug treatment.

Introduction in those aged > 75 years; thus, it is reasonable to expect that the overactive bladder (OAB) sickness rate will also increase. The current outlook of the European population reveals an The abundance of overactive bladder increases permanently increasing proportion of people aged > 65 years old, with a rise in association with an increasing average, susceptible to its

KEYWORDS: Overactive bladder, aging population, pharmacologic treatments, muscarinic antagonists, side effects, tolterodine, trospium, oxybutynin, solifenacin, combination antimuscarinics, urodynamic monitoring CORRESPONDENCE: Kirill Kosilov, Far Eastern Federal University, Department of Neurourology-Urodynamics, Primorsky Regional Diagnostic Center, Vladivostok, Russian Federation ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 47. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.06

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.06 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study influence on 41% of men and 31% of women aged > 75 years other coexistent diseases that limit their ability to remain dry. [1,2]. Many older women use pads to manage the problem. Men are more likely to seek earlier help because of the recognized The occurrence of OAB also has important quality-of-life and association between lower urinary tract symptoms (LUTS) and economic consequences, and the presence of incontinence is prostatic pathology. associated with a greater likelihood of nursing-home placement and other adverse factors [9-13]. As it is known, OAB is a chronic disorder characterized by symptoms of urinary urgency with or without urgency Although treatment for idiopathic OAB has been extensively incontinence, usually accompanied by frequency and nocturia studied, therapy for the elderly population has not been in the absence of infection or obvious neurologic pathology. thoroughly evaluated. Long years of research and multiple The OAB-symptom complex is the commonest cause of urinary clinical studies with antimuscarinic drugs have proved their incontinence in the elderly, usually due to underlying detrusor effectiveness in treating neurogenic bladder dysfunction. overactivity, and as such is a treatable condition [1,2]. The elderly, as a rule, have more severe disease than younger Most elderly patients have already received oral antimuscarinic people. Studies using urodynamic data show that senior citizens treatment. Nevertheless, for some older patients, these with OAB have a depressed bladder capacity and usually have antimuscarinic drugs often fall short because of insignificant urgency at lower volumes of filling than younger adults with effect taken on the continuing incontinence [1,3,5,14]. Several this status, despite the fact that older adults with no evidence articles on this issue noted that side effects with increasing of OAB have a depressed sensation of bladder filling [3]. The dosages and the number of drugs did not occur more often or elderly patient’s main problem is involuntary loss of urine more severely than with the recommended dosage of a single induced by sudden and strong bladder retraction that causes drug [15]. Based on initial research with the population of stress in patients, resulting in a distinct reduction in quality of elderly patients, we have assumed that another antimuscarinic life [4]. drug could be combined with the existing medication to advance the continence, bladder capacity, and pressure in the For many cases of OAB, the underlying etiology is not entirely bladder. understood. The forming of idiopathic OAB is often one of the symptoms associated with weakening nervous system Patients and Methods effectiveness as a whole in the elderly population. In the older bladder, there is an increase in the collagen-to-muscle ratio and The study was a double-blind, phase II clinical trial with 2 parallel a decrease in the amount and level of innervation, resulting in treatments, performed in the Regional Diagnostic Center in less cholinergic transmission [5]. This is reflected in a negative Vladivostok, Russia. From 2008 to 2010, 81 patients older than correlation of receptor numbers in the detrusor muscle as 65 years, both male and female, who earlier received double- people age and selective age-related decreases in mRNA for doses of antimuscarinic monotherapy (trospium), whose initial muscarinic M3 (but not M2) receptors in both male and female symptoms did not resolve and who experienced mild or no side bladders. These findings correspond with reports of decreased effects, were enrolled. detrusor contractility with aging, and many of them occur in response to obstruction and ischemia. The role of suburothelial In accordance with the experience protocol, patients with OAB M2 receptors in DO is now better understood. They are well had to be 65 to 79 years of age, with normal body weight, vital preserved in older bladders and might be involved in the signs, and age-appropriate ECG. Therefore, the study group appreciation of urgency [2,6]. consisted of 51 male and 30 female patients with the average age of 67.9 years (range: 65–79 years).

As reported by several researchers, OAB-associated diseases The main signs of exclusion included closed-angle glaucoma, include neurological impairment (multiple sclerosis, spinal tachydysrhythmias, urinary outlet obstruction, myasthenia cord injury), neurological degeneration (Parkinson’s disease, gravis, allergies, and other severe diseases. Contemporaneous multi-system atrophy), and bladder outflow tract obstruction. treatment with other anticholinergics, antidepressants, The underlying cerebrovascular disease and lumbar a-blockers, and b-sympathomimetics was not allowed. The spondyloarthropathy have also been associated with the experience was performed in accordance with Good Clinical development of DO in older men with prostatic disease [7]. Practice (GCP) and the Declaration of Helsinki [16]. Prior written Other associated conditions include UTIs, skin infections, sleep and informed consent on the study was obtained from each disorders, urogenital atrophy, and depression [8]. Reduced patient. The study was agreed and approved by the local ethics physical and cognitive function with aging and the influence committee. of coexisting medication are already known to be important. Older people might be unable to compensate for the impact of Patients in the group showed (both in the antecedent study

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.06 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study and present study) urodynamically proven idiopathic OAB patient carried out a urodynamic examination to confirm the dysfunction with incontinence, reduced bladder capacity, and diagnosis of OAB. The urodynamic state of the lower urinary increased intravesical pressure. Based on previous surveys, using tract was evaluated in accordance with the International double monotherapy, the patients in the present study were Continence Society (ICS) guidelines [16, 21]. allocated into 3 pre-determined treatment groups; we took the double-dose drug from the initial study and added the second A UDS “Relief-01” (DALPRIBOR, Vladivostok, Russia) with antimuscarinic drug at the usual recommended dosage to reduce double catheter (8 Ch; 1,7 I.D., 2,7 O.D., Apexmed International any risk of adverse events [4,15]. We decided to proceed with B.V., Netherlands) was used for the standard urodynamic the drug from the primary study (trospium), because this drug procedure. The following data was recorded and analyzed: 1) was well tolerated by the patients, and added 3 new drugs, 1 maximal bladder capacity, 2) reflex volume of the bladder, 3) for each group. Patients were accurately monitored for 6 weeks maximum detrusor pressure, and 4) detrusor compliance. under a consistent drug setting for possible side effects. The dosage of each of these drugs was changed as needed according The bladder was filled with 98.6 °F of isotonic solution (0.9% to patient feedback and a review of their diaries while ensuring NaCl) via the transurethral micro-tip catheter at the filling rate that the combination was uneventfully generally tolerated and of 20 mL/min. For calculating the pressure in the bladder, a urodynamic results were also sufficiently positive. rectal balloon catheter was inserted into the rectum to register the intra-abdominal pressure. The urodynamic unit also Statistical Methods recorded the pelvic floor muscle activity by electromyogram with adhesive electrodes attached to the perineum. The indicators were processed with Excel (Microsoft-Rus, Moscow, Russia) and analyzed with SAS JMP Statistical Discovery Pending the survey and the 6-week and 4-month follow-up 8.0.2 (SAS Institute, Cary, NC, USA). Wilcoxon and Kruskal-Wallis under the effective or tolerated antimuscarinic dosage, the tests were used to compare results in each treatment group patients underwent urodynamic examination. Urodynamic before and after supplement of another drug. The one-way parameters for effective treatment were defined as follows: analysis of variance (ANOVAs) with the Tukey-Kramer method 1) intravesical pressure less than 40 cm H2O, 2) less than 2 were used to compare effects in the 3 groups; a post-hoc analysis incontinence events per day, 3) a bladder capacity of at least was performed for individual changes in each of the criteria. P 300 mL, and 4) a bladder compliance greater than 25 mL/cm values of < 0.05 were considered statistically significant. H2O. The study terminology and the urodynamic parameters followed the International Continence Society guidelines [16]. Urodynamic Studies Bladder Diaries It is known that urodynamic studies reproduce the patient’s symptoms during the test to assure the validity of urodynamic All participants of this survey had a bladder diary at their findings. This is not always easy for several reasons, particularly disposal to fix the amount of urine while urinating, mark the in the elderly. Such a survey is performed in unfamiliar time of taking medications, the time and amount of fluid intake, surroundings, which includes the presence of the examiner and incontinence events and their description, as well as occurrence staff as well as the equipment. of side effects. The fluid intake recording was necessary to ensure a patient’s constant hydration during the study [22-24]. In addition, the insertion of 1 or 2 catheters transurethrally into the bladder and 1 more catheter into the rectum can be quite Treatment Algorithm uncomfortable. A number of potential pitfalls may have been encountered in a urodynamic study relating to fluid fill rate and Group A (N = 27; mean age 69.1 yr; SD ± 8.9) received 60 mg the level of the liquid temperature, the patient’s position, and of trospium and oxybutynin dosages between 10 and 25 mg the presence of significant genital prolapse. However, despite (Table 1). Group B (N = 31; mean age, 68.2 yr; SD ± 8.4) received all these features, most researchers recognize urodynamics as a 60 mg of trospium and tolterodine dosages between 4 and 8 secure and completely reliable method of studying the state of mg. Group C (N = 23; mean age, 66.8 yr; SD ± 5.9) received 60 lower urinary tract health in the elderly [17-20]. mg of trospium and solifenacin dosages between 20 and 40 mg.

Before the start of the study, the urine status was verified to Results exclude incorrect measurements due to urinary infection. If any urinary infection had been found, the patient received Reports on Side Effects an appropriate treatment and was examined again in 2 to 3 weeks. If the infection had been found repeatedly (2 episodes), All patients had to pay attention to and describe the following the patients were excluded from the study. In addition, each disorders in their diaries: dry mouth, blurred vision, dizziness,

Table 1. Dosing of antimuscarinic drugs to patients in the target groups (n = 81).

Ordinal day of treatment 1 2 3 4 5 6 7 8 9 10 11 12 13 14 23 37 Group of patients Recom. dosage Doubled dosage 41 Last day of the study

Group A First 30 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 qty. of patients: 27 trospium (mg)

Second 10 10 15 15 20 20 25 25 15 15 20 20 20 20 20 20 20 oxybutynin

(mg) First study Second study

Group B First 30 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 qty. of patients: 31 trospium (mg)

Second 4 4 4 4 8 4 4 6 6 6 6 6 6 6 6 6 6 tolterodine (mg)

Group C First 30 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 qty. of patients: 23 trospium (mg)

Second 20 20 20 20 40 40 40 20 20 20 20 30 30 30 30 30 30 solifenacin (mg) Total time of the study: 6 weeks Remark: Gray shading = dropouts due to side effects; hazel shading = dropouts due to unsatisfactory outcome

nausea, vomiting, rash, dry skin, nervousness, sleep disorders, Results Urodynamic and Bladder Diaries cognitive impairment, memory impairment, hallucination, confusion, stomach pain, bloating, or gas, as well as any other In all groups, positive results were observed. In group A (trospium breach of health [25,26]. Twenty-eight patients reported side + oxybutynin), the incontinence events reduced from the range effects under the combined therapy with 2 antimuscarinic of 3 to 11 (median 6.3), to 0 to 5 (median 2.3). The urodynamic drugs (Table 2). study found an increase in reflex volume (from a median of 165 mL to 291) as well as an increase in maximal bladder capacity Twenty patients had poorly expressed side effects; therefore, (183 to 320 mL) and increased bladder compliance (22 to 35 the combined therapy was continued. In 3 remaining patients, mL/cm H2O). In group B (trospium + tolterodine) incontinence the combined therapy was stopped soon after the beginning events reduced from the range of 3 to 13 (median 5.5) to 0 to 4 of the study because of the side effects (in 2 cases, it was (median, 2.4). Reflex volume increased from the median of 135 intolerable dry mouth (groups A, C), in 1 case, insomnia (group mL to 265 mL and increased as the maximum capacity of the A)) despite their attaining objective and subjective treatment bladder from 171 mL to 380 mL was recorded, and the bladder success. compliance advanced from 10 to 35 mL/cm H2O. In group C (trospium + solifenacin), the incontinence events reduced from Eliminated Because of Poor Results the range of 4 to 15 (median 7.5) to 0.5 to 5 (median 2.2). Reflex volume in patients in this group increased (median 130 Seven patients (3 patients in groups A and B, and 1 in group to 295 mL), and the maximal capacity increased from 175 to 340 C) did not experience any satisfactory benefit or improvement mL, with detrusor compliance increasing from 13 to 39 mL/cm under the combined antimuscarinic therapy (Table 1 and Table H2O (Table 3). Table 3 shows the same average values for all 3 2), although they also received double doses of the second groups. antimuscarinic drug. As mentioned above, improvement was noted in all groups.

Table 2. Side effects and patients dismissed. results were not reported separately.

Group A Group B Group C Parameters such as “frequency of urination during daytime” and Dry mouth 4 (1) 2 (0) 1(1) “frequency of urination at night” were down in synchronization with events of incontinence, but the significance of differences Blurred vision 1 1 2 in most cases was not sufficient. Index Sudden Urge (urgency) Dizziness 1 1 0 correlated with incontinence events, and it was noted as a Nausea, vomiting 0 1 0 significant decrease in all groups with P < 0.01. Rash 2 0 0 Discussion Dry skin and intense 2 0 1

itching The practice of antimuscarinic therapy as the priority medication Nervousness 0 0 1 for the control of overactive bladder in the elderly is well Sleep disorders 2 (1) 0 0 established, and the effectiveness of antimuscarinics for the Cognitive 0 0 0 treatment of OAB is well documented. In general, antimuscarinic impairment therapy is most effective in older patients with relatively mild to moderate bladder dysfunction [27-30]. Patients seeking help Memory impairment 0 0 0 are usually concerned about urinary incontinence, frequent Hallucination 0 0 0 urination, and an urgent need to urinate, which decreases their Confusion 0 0 0 quality of life. Receiving antimuscarinic drugs contributes to Stomach pain, 1 0 0 full or a partial relief of symptoms, but side effects such as dry bloating, gas mouth, blurred vision, dizziness, nausea, vomiting, rash, dry Other breach of 1 0 0 skin and intense itching, sleep disorders, and some others are health extensively described by many authors and must be reconciled [31,32]. Discontinuation due 2 0 1

to side-effects The action of antimuscarinic agents on detrusor muscles is well Discontinuation due 3 3 1 researched today. Oxybutynin hydrochloride is a moderately to unsatisfactory potent antimuscarinic agent with pronounced detrusor muscle outcome relaxant activity. Oral administration effectivity has been shown Remark: Parentheses indicate the number of cases to refusal of further therapy because of side effects. in many publications. Its effectiveness has been established and described by many researchers [33]. Trospium effectiveness and safety was confirmed many times by meta analysis as well. It does not break the blood–brain barrier, and central nervous system side effects are therefore not expected [34]. Tolterodine is a competitive muscarinic receptor antagonist with better With regard to episodes of incontinence, group C showed tolerability and comparable efficacy than in oxybutynin. Many somewhat greater improvement after treatment compared authors have noted the therapeutic effect of increasing doses of with other groups, but differences were not statistically the drug. Tolterodine was also one of the first new-generation significant (P = 0.78). Enhancement of reflex volume was antimuscarinics that was better tolerated due to reduced equally and highly statistically significant in groups A and C side effects [35]. According to some researchers, significant (P < 0.001, ANOVA) and slightly lower in group B (P < 0.005, improvements in urgency and other diary-documented ANOVA). The most significant improvement in terms of bladder symptoms of OAB were noted in patients with urgency and capacity was observed in patients of group B (P < 0.0005, other symptoms of overactive detrusor after treatment with ANOVA), and difference indicators in 2 other groups were also solifenacin. Patients receiving solifenacin also had significant at acceptable levels. Finally, the assessment of bladder function improvements in HRQL. Moreover, solifenacin, with its flexible by the criterion of detrusor compliance found that the most dosing regimen, was found to be superior to tolterodine with significant differences in comparison to the original data were respect to the majority of the efficacy indicators [36,37]. available in groups B and C (P < 0.001, ANOVA). Nevertheless, after the use of antimuscarinics at the The results shown are derived from the 6-week evaluation. The manufacturer's recommended dosage, approximately 1/3 of final evaluation (diary and urodynamic) was performed at the patients still do not experience sufficient efficacy [4,38]. In order fourth month, the results of which were almost identical to the to improve the effectiveness of treatment in these patients, we 6-week follow-up. As a result of this similarity, the 4-month attempted to optimize the treatment. As it was established

Table 3. Comparative analysis of urodynamic and diary data in groups A, B, and C (n = 81 ).

Bladder diary importance (± SD) Urodynamics importance (± SD) Incontinence events Sudden Urge /day Frequency of Frequency of Detrusor compliance / day urination during urination at night Reflex volume (ml) Bladder capacity (ml) (ml/cm H O) daytime 2 Before After Before After Before After Before After Before After Before After Before After treat treat Group A 6,3 2,3 10,9 (3,6) 3,5 5,6 (0,8) 5,1 2,1 (0,3) 0,7 165,7 291,2 (trospium+ (2,0) (1,1)* (1,0)** (0,9) (0,4)* 183,5 320,3 22,4 (7,6) 35,6 (23,2) (61,2)** oxybutynin) (27,8) (42,2)** (9,0)* Group B 5,5 2,4 9,8 (2,1) 4,1 6,1 (0,5) 4,8 1,5 (0,8) 0,9 (0,4) (trospium+ (2,6) (1,2)* (1,7)** (0,4)* 135,4 265,9 170,8 380,1 10,8 (1,2) 34,9 tolterodine) (30,0) (31,9)* (11,9) (34,8)*** (6,9)** Group C 7,5 (2,0) 2,2 10,1 (2,6) 3,1 6,6 (1,3) 5,8 (1,5) 1,5 (0,4) 0,7 (0,5) (trospium+ (0,9)** (2,0)** 130,7 295,5 175,5 340,0 13,6 (4,4) 39,1 solifenacin) (17,9) (41,3)** (33,5) (49,8)** (4,1)** 6,2 (2,2) 2,1 (1,0)* 10,4 (2,2) 3,6 6,0 (1,7) 5,3 (1,9) 1,7 (0,3) 0,8 148,9 283,8 176,9 356,6 15,7 (3,4) 37,1 All groups (0,7)** (0,2)* (24,7) (34,8) (39,9) (41,8)** (5,7)** Remark: SD = standard deviation.* < 0.05; ** < 0.01; *** < 0.005. “Before” amounts taken at onset of study and considered baseline; “after” amounts taken at 6-week follow-up.

earlier [4,15], increased administration of antimuscarinic drugs was the greatest in group C, and the largest increase in absolute was tolerated well. Therefore, we assumed that, since our values in the bladder capacity was found in group B. The most patients did not experience a benefit from the doubled dosage significant increase in the values of detrusor compliance was in the first study, a different combination of antimuscarinics also noted in group C. The number of episodes of incontinence (with modified receptor selectivity) might be beneficial and decreased most significantly in group C, as well. Differences in result in an inconsiderable increase in side effects only. Thus, the dynamics of these indices between groups were statistically we decided to increase the initial dose of the antimuscarinic insignificant. drug 1.5 to 2 times and introduce the second antimuscarinic drug in the second phase. Nearly 2 decades ago, it was found that the action of antimuscarinic agents was to suppress overactive contractions We did not know of that decision before, but we knew that of the bladder acting via M3- receptors, although data to a group of authors [4] used combined treatment with high support this were inconsistent [41]. It is now well known that doses of antimuscarinic drugs. However, these researchers that the M2-muscarinic receptor is the predominant receptor in used a different combination of drugs and the study was the urinary bladder. M3-muscarinic receptors are represented not conducted specifically in elderly patients. In addition, we in a lower amount but they are more efficient. It is also known investigated the greatly expanded list of side effects studied. that pre-junctional–inhibiting M2- or M4-muscarinic receptors, as well as M1-muscarinic receptors, were detected in the urinary As in most similar studies, in the beginning, the majority of bladder. The interaction of the subdivision of these muscarinic patients experienced feelings of anxiety because of increased receptors is currently not well understood. Currently, there are side effects due to the use of a second antimuscarinic, which strong indications of the presence of muscarinic receptors in soon disappeared. In the data (Table 3) for our all study groups, various tissues, including M1-receptors in the brain, sympathic which were obtained in a population of elderly patients, ganglia, and salivary glands; M2-receptors in cardiac tissue our statistical analysis demonstrated confident results with (heart frequency), brain, and smooth muscle (bladder and an increase in reflex volume, maximal bladder capacity, and stomach); M3-receptors in salivary glands, eyes, and especially detrusor compliance under the combined treatment. The main smooth muscle (bladder contraction, intestinal movement, positive clinical result, the improvement of patient quality of accommodation); M4-receptors in the brain and salivary glands; life, with an acceptable level of confidence, was connected with and M5 receptors in the brain, eyes, and also the urinary bladder reduction of incontinence events [39,40]. The most patients [35,42,43]. were positive that the declined frequency of incontinence events positively affected their quality of life. It is also believed that trospium with its continuous affinity to all receptors (M1 to 5) showed milder side effects; this is why In all 3 groups satisfactory options for urodynamic parameters we chose it as the basic antimuscarinic drug for all 3 groups of and patient satisfaction were achieved. Reflex volume increase elderly patients.

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©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.06 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Prevalance of Prostate Carcinoma in the Indian Population: The Need to Revise Serum Prostate Specific Antigen (PSA)

Nandan R. Pujari Submitted March 21, 2013 - Accepted for Publication July 22, 2013 Abstract

Introduction: This prospective study is an attempt to revise the serum prostate specific antigen (PSA) cutoff level to suit the Asian population. Materials and Methods: A prospective study was carried out on 172 male patients who underwent transrectal ultrasound (TRUS) prostate biopsies. Only those patients with a serum PSA level within the range of 4 to 10 mg/ mL were included in this study. The decision to perform the biopsy was undertaken only after further evaluation using free:total PSA ratio. Results: Of the 172 patients, 9 (5.23%) patients had adenocarcinoma prostate with a Gleason's score ranging from 4 to 7. In total, 163 (94.7%) patients had benign pathology. Serum PSA ranged from 4.2 to 9.8 ng/mL. Conclusion: The cutoff level of serum PSA beyond which investigations are warranted in Asians is controversial at present, and further multicentric trials involving a larger number of\ patients must be carried out to arrive at a consensus.

introduction biopsies. Their age ranged from 57 to 72 years (mean age: 65.2 years). They had initially presented with lower urinary tract Serum prostate specific antigen (PSA) is an invaluable tool for symptoms in the urology clinic. All patients underwent detailed the detection, staging, and monitoring of men diagnosed with clinical examination, including a digital rectal examination prostate cancer. After the clinical application of serum PSA, (DRE). All patients underwent serum PSA examination and an identification of cancers confined to the prostate has improved ultrasound examination of the abdomen and pelvis. Only those curability. Prostate cancer is the fourth most common male patients with serum PSA levels within the range of 4 to 10 mg/ malignant neoplasm worldwide; however, the incidence and mL were included in this study. Patients on anticoagulants were prevalence of carcinoma prostate in Asia is the lowest in the not included in the study. Patients with an active urinary tract world, but the serum PSA cutoff value is treated within the same infection were included in the study only after the infection was range as their Western counterpart. This leads to unnecessary treated and the urine culture showed no growth of organisms. investigations in this patient populace. Our prospective study is The decision to perform the biopsy was undertaken only after an attempt to revise the serum PSA cutoff level to suit the Asian further evaluation using free:total PSA ratio. A free:total PSA population. ratio cutoff of 0.18 was considered the selection criteria for biopsy. An extended core biopsy technique (12 or 13 cores) Materials and methods was used for performing the transrectal prostate biopsies. All patients received antibiotics prior to the biopsy. A single team A prospective study was carried out on 172 male patients with performed biopsies, a single pathologist saw histological slides, serum PSA level within the range of 4 to 10 mg/mL and who and PSA was determined in the same laboratory using a single underwent transrectal ultrasound-(TRUS) guided prostate method. All these conditions were maintained to minimize

KEYWORDS: Prostate carcinoma, serum PSA, Asian population, adenocarcinoma CORRESPONDENCE: Nandan R. Pujari, MS, DNB (Urology), MGM Medical College, Mumbai, Maharashtra, India (pnandan20@gmail. com) CITATION: UroToday Int J. 2013 August;6(4):art 51. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.10

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.10 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study statistical fluctuation due to interobserver variability. Figure 1. A graph depicting the number of patients with benign and malignant histopathology. All patients were asked to follow up 1 week after the biopsy. During the follow-up visit, clinical examination was performed and histopathology reports were reviewed. The most common complication was hematuria, which subsided spontaneously in all patients. None of the patients developed clot retention. Three patients developed urinary infection, which subsided with oral antibiotics. Seven patients reported hematospermia, which subsided by 2 to 3 weeks. Four patients developed urinary retention, which required catheterization. All 4 patients responded to tamsulosin and passed urine on a trial void after 1 week. Patients with adenocarcinoma of the prostate were then further investigated (computed tomography scan and bone scan) and were staged accordingly.

Results

Of the 172 patients, 9 (5.23%) patients had adenocarcinoma of the prostate with a Gleason’s score ranging from 4 to 7 (mean: 5.3). Six patients had organ-confined disease of which 4 Figure 2. A graph depicting the percentage of malignancy patients underwent radical prostatectomy and 2 patients opted in the range of serum PSA of 4 to 10 ng/mL. for watchful waiting. Three patients had metastatic disease and underwent bilateral orchidectomy. One hundred and sixty- three (94.7%) patients had benign pathology (Figure 1). Serum PSA ranged from 4.2 to 9.8 ng/mL. One patient had high-grade prostatic intraepithelial neoplasia (HGPIN) and has undergone repeat prostate biopsy twice with similar histopathology reports. This patient is on close follow-up. None of the patients had atypical small acinar proliferation (ASAP).

Discussion

Among urologic malignancies, prostate cancer has greatly benefited from the discovery and application of tumor markers. Since its discovery in 1979 to clinical application in the late 1980s, PSA has evolved into an invaluable tool for the detection, staging, and monitoring of men diagnosed with prostate cancer [1,2]. Whereas the majority of prostate cancers in the 1980s and early 1990s commonly arose with an abnormal digital rectal levels may reflect alterations within the prostate secondary examination (DRE) or elevated PSA, or both, today most prostate to tissue architectural changes such as cancer, inflammation, cancers arise as clinically non-palpable (stage T1c) disease with or benign prostatic hyperplasia (BPH). Currently, serum PSA a PSA between 4 and 10 ng/mL. The evolving demographics levels as low as 2.6 ng/mL are used as a threshold to perform and natural history of prostate cancer have resulted in a stage transrectal ultrasound-guided biopsy in Western literature. migration to non-palpable, clinically localized (stage T1c) Although up to 30% of men presenting with an elevated PSA disease and a parallel reduction in mortality [3,4]. Although PSA may be diagnosed following this invasive procedure, as many screening has improved survival, outcomes are not the same for as 75 to 80% are not found to have cancer. To this end, the all T1c detected disease as some of these cancers may not pose a application of PSA derivatives such as PSA density, PSA velocity, threat to survival [5]. Despite routine application of PSA assays, age-adjusted values, and, more recently, molecular derivatives limitations of specificity for this marker remain. Although have attempted to improve the performance of PSA [6,7]. The PSA is widely accepted as a prostate cancer tumor marker, it majority of men with PSA elevations have serum levels in the is organ specific and not disease specific. Unfortunately, there range of 4 to 10 ng/mL [8]. In these men, the most likely reason is an overlap in the serum PSA levels among men with cancer for PSA elevation is prostate enlargement, not prostate cancer, and those with benign disease. Thus, elevated serum PSA because of the high prevalence of BPH in this population.

Table 1. Distribution of studied cases by age, other showing an increased incidence of prostate cancer in first variables, and biopsy outcome. generation immigrants to the United States from Japan and China [10]. These observations suggest that diet may play a Biopsy Biopsy role in converting latent tumors into clinically manifest ones. Outcome Outcome A strong positive correlation exists between prostate cancer Variable Values Cancer Benign Cancer % incidence and the corresponding rates of several other diet- age 50-59 1 62 1.6 related cancers, including breast and colon cancers [12]. 60-69 5 92 5.43 The positive predictive value of PSA testing for cancer detection 70-79 3 18 16.66 increased from 12 to 32% for PSA levels of 4 to 10 ng/mL and total PSA 4-7 2 88 2.27 as high as 60 to 80% for levels above 10 and 20 ng/mL [13]. (ng/mL) Thus, men with PSA levels greater than 10 ng/mL and benign 7-10 7 84 8.33 DRE have up to a 60% likelihood of being diagnosed with cancer and are unlikely to benefit from further improvement DRE suspicious 3 169 1.77 of PSA sensitivity and specificity. Thus, men with PSA levels DRE: digital rectal examination greater than 10 ng/mL are encouraged to undergo a biopsy regardless of PSA derivative values. For men with PSA levels between 4 and 10 ng/mL, the specificity of cancer detection has been more challenging. Cancers discovered within this range are often earlier in stage, and potentially curable, yet might represent “insignificant,” potentially non–life-threatening The lifetime risk (from age 0 to 90 years) of death from prostate tumors. However, due to the considerable overlap in serum cancer is 3% and the lifetime risk of a diagnosis of prostate PSA concentrations in men with and without prostate cancer, cancer is 17% (Surveillance, Epidemiology, and End Results this range has been described as the diagnostic “gray zone.” [SEER] Program). The incidence of carcinoma prostate varies Efforts to improve the diagnostic accuracy of PSA within this widely between countries and ethnic populations, and disease diagnostic gray zone include PSA density, PSA velocity, and rates differ by more than 100-fold between populations. age-specific PSA. The lowest yearly incidence rates occur in Asia (1.9 cases per 100,000 in Tianjin, China) and the highest in North America The literature describes the prevalence of adenocarcinoma and Scandinavia, especially in African Americans (272 cases prostate in the range of 4 to 10 ng/mL, with a serum PSA of up to per 100,000) [9]. Mortality also varies widely among countries, 32% (Figure 2). In our series the prevalence is far lower (5.23%) the highest being in Sweden (23 per 100,000 per year) and the than that described in the literature (P value: < 0.0001). A P lowest in Asia (< 5 per 100,000 per year in Singapore, Japan, value < 0.05 is significant. The P value was calculated using the and China) [9]. Z test for proportion. This corresponds to the low incidence and mortality rate for adenocarcinoma prostate described among There are multiple complex causes for the worldwide and ethnic Asians. This data supports our opinion regarding revising of variations in prostate cancer incidence. Environment plays an the cutoff value for serum PSA among Asians beyond which important role in modulating prostate cancer risk around the further investigations and biopsy should be planned to avoid world. Japanese and Chinese men in the United States have a the diagnosis of clinically insignificant cancers in this gray zone. higher risk for the development of prostate cancer and dying of it than do their relatives in Japan and China [10]. Likewise, Conclusion prostate cancer incidence and mortality have increased in Japan as the country has become more westernized [11]. However, The cutoff level of serum PSA beyond which investigations are Asian Americans have a lower prostate cancer incidence than warranted in Asians is controversial at present, and further white or African American men do, indicating that genetics still multicentric trials involving a larger number of patients must be plays a role in determining prostate cancer predisposition. carried out to arrive at a consensus, since blindly following the current Western literature results in unnecessary interventions Studies suggest that dietary factors may contribute to prostate in this patient population. Methods for improved detection of cancer development [12]. The incidence of latent prostate clinically significant prostate cancer are needed. cancers is similar around the world, but the incidence of clinically manifest cancers differs, with Asians having the lowest rates of clinical prostate cancer. The most convincing evidence for the role of the diet and other environmental factors in modulating prostate cancer risk comes from migration studies

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©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.10 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Common Laboratory Values Are Unreliable in Identifying the Presence of Metastatic Renal Cell Carcinoma in the Liver and Bones

Joshua E. Logan, David A. Staneck, Mary H. James, Jack W. Lambert, Robert W. Given, Raymond S. Lance, Michael D. Fabrizio, Stephen B. Riggs Department of Urology, Eastern Virginia Medical School, Norfolk, Virginia, USA Submitted April 16, 2013 - Accepted for Publication July 14, 2013 Abstract

Introduction: Evaluation of patients with newly diagnosed renal cell carcinoma (RCC) often includes evaluating serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Traditional teaching is these laboratory values, if elevated, may indicate the presence of metastatic disease to the liver (AST and ALT) or bones (ALP). We analyzed our institutional RCC database to determine how consistently aberrations in these values were present when metastatic RCC was present. Materials and Methods: A retrospective chart review was completed, identifying 315 patients diagnosed with RCC who had AST, ALT, and ALP values available for review. Overall rates of aberration, as well as rates of aberration in those patients presenting with metastatic RCC, were calculated. Results: Of the 315 patients in the study cohort, 61 (19.4%) presented with an elevation in 1 or more of the laboratory values in question. Of these 61 patients, 58 (95%) presented with clinically localized disease. The remaining 3 patients (5%) presented with lung metastasis identified on imaging and had isolated elevations of ALP ranging from 130 IU/L to 278 IU/L; these 3 patients were of the 9 in the cohort who presented with lung metastasis. Five patients presented with metastatic lesions to the bone with no elevation of ALP present. Five patients presented with metastatic lesions to the liver, and none of these patients had any elevation of ALT or AST. However, 1 of these 5 patients did have minimal elevation in ALP, 130 IU/L, but also had a concomitant lung metastasis. Conclusion: Elevation in ALP, while not seen in patients with bone metastasis in this cohort, was present in 33.3% of patients presenting with lung metastasis. Therefore, an identified aberration in ALP may be considered to direct closer pulmonary evaluation. Regarding AST and ALT, elevations of these laboratory values were not present in any patients with liver metastasis. These observations highlight that AST, ALT, and ALP are unreliable in suggesting the presence of metastatic RCC lesions in liver or bone, and underscore the importance of imaging.

Introduction (ALP). AST, ALT, and ALP are all expressed in liver tissue as well as other tissue types, including ALP expression in bone Patients that have been referred for evaluation and [1]. Elevations in 1 or more of these enzymes may herald any management of a renal mass routinely undergo radiographic number of entities. Specifically of interest in this population as well as metabolic evaluation. Metabolic evaluation often would be the presence of metastatic renal cell carcinoma (RCC). includes a comprehensive metabolic panel, which provides Campbell-Walsh Urology indicates that these changes may information regarding aspartate aminotransferase (AST), indicate advanced disease, which is consistent with traditional alanine aminotransferase (ALT), and alkaline phosphatase teaching: An elevation in any of the 3 enzymes may indicate

KEYWORDS: Renal cell carcinoma, metastases, laboratory values, AST, ALT, alkaline phosphatase CORRESPONDENCE: Joshua E. Logan, MD, Fellow, Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, California, United States ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 46. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.05

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.05 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study hepatic metastasis, while elevations in ALP may indicate bone Figure 1. Categorization of 315 patients with RCC metastasis [2]. according to AST, ALT, ALP, and metastatic status.

With high-quality cross-sectional imaging available for patients diagnosed with a renal mass, some liver and bone lesions can be identified depending on the technique of the study and the regional extent of imaging [3,4]. Given that some liver or bone metastases may be missed radiographically, it would be useful to have an adjunct that reliably identified metastases to 2 of the more common sites of metastasis for RCC. To our knowledge no report has been published indicating how consistently AST, ALT and ALP indicate the presence of liver or bone metastases in patients with RCC.

Materials and Methods

We reviewed our institutional RCC database and identified 315 patients for whom a complete data set was available, including AST, ALT, and ALP values, as well as radiographic Of these 61 patients with elevated enzymes, 58 (95%) presented information regarding the presence and location of metastasis. with clinically localized disease. The remaining 3 patients Patients were excluded if this data was unavailable for review. (5%) presented with lung metastasis identified on imaging Institutional standards of normal ranges for each laboratory and had isolated elevations of ALP ranging from 130 IU/L to value are as follows: AST 5-37 IU/L; ALT 5-40 IU/L; and ALP 25- 278 IU/L; these 3 patients were of the 9 in the total cohort 115 IU/L. Patient history of bone or hepatic disease, which could who presented with lung metastasis. Five patients presented have also accounted for elevations of enzymes in the absence of with metastatic lesions to the bone with no elevation of ALP metastatic RCC, was unavailable for review; however, it should present. Five patients presented with metastatic lesions to the be noted that elevated enzymes, regardless of cause, were liver, and none of these patients had any elevation of ALT or evaluated appropriately. A history of alcohol consumption was AST. However, 1 of these 5 patients did have minimal elevation only recorded as yes or no; quantity data was not available for in ALP, 130 IU/L, and also had a concomitant lung metastasis. review. Computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis were available for It should be noted that of the 315 patients, 275 (87.3%) review on all patients in the cohort. A chest X-ray was also reported on alcohol consumption, and 166 (60.4%) of those available for review in all patients, and a chest CT was available patients reported that they did consume alcohol. Of the 61 in some patients. The indication for chest CT varied between patients with elevated enzymes,. 28 reported no consumption patients and did not necessarily indicate an abnormal chest of alcohol, 21 reported that they do consume alcohol, and 12 X-ray. Bone scans were only obtained if there was reasonable had an unknown alcohol consumption status. clinical suspicion for the presence of bone metastasis. Overall, aberration rates of AST, ALT, and ALP were calculated, as well The overall categorization of patients is demonstrated in Figure as for each enzyme, respectively. We also calculated the rates 1, and the sensitivity, specificity, positive predicted value, and of aberration specifically in those patients presenting with negative predictive value for each enzyme have been calculated metastatic RCC. and presented in Table 1.

Results Discussion

Of the 315 patients in the study cohort, 61 (19.4%) presented The evaluation of common laboratory values as part of patient with an elevation in 1 or more of the laboratory values in work-up for RCC is commonplace. While the practice of obtaining question. Elevations in AST were identified in 19 (6.03%) of an extended chemistry panel serves more than 1 purpose, it has the patients; elevations in ALT were identified in 23 (7.30%) been used in part to grossly survey for the presence of liver or of the patients; and 33 (10.5%) of the patients had elevations bone metastasis, as the presence of metastasis would change in ALP. Of the 33 patients with ALP elevations, 29 (88.7%) had the clinical picture and potentially change the management no elevations in the other 2 enzymes. Whereas 8 (42.1%) of the plan. Campbell-Walsh Urology does not state that this practice 19 AST elevations were AST only, and 11 (47.8%) of the 23 ALT is considered standard to the evaluation, but it does state elevations were ALT only. that it may indicate the presence of advanced disease. The understanding as to why these changes can be detected in

Table 1. Predictive values for AST, ALT, and ALP in non-metastatic, nephrogenic hepatic dysfunction [6]. Others identifying the presence of metastatic RCC. may have been secondary to non-related bone pathology or hepatobiliary dysfunction, such as secondary to alcohol Sensitivity Specificity PPV NPV consumption, as discussed above. However, regardless of the AST for liver metastases 0% 94% 0% 98% cause, it remains that elevations did not routinely identify ALP for liver metastases 20% 90% 3% 99% metastasis to the liver and bone per the traditional teaching. The elevated ALP identified in a third of the patients in this cohort ALT for liver metastases 0% 89% 0% 98% with lung metastasis did raise the question of whether or not ALP for bone metastases 0% 89% 0% 98% an elevated ALP could be useful in identifying lung metastasis. ALP for lung metastases 33% 90% 9% 98% This would require confirmatory studies with electrophoresis to ensure that the elevated ALP is the pulmonary-specific isozyme. This may be a worthwhile pursuit given that an elevated ALP has been reported to have negative predictive value on survival in RCC patients [7,8]. More generally, given that ALP is known to predict adverse outcomes in RCC patients, ALP should be further the laboratory values is related to the destructive nature of investigated as to its value in risk stratifying RCC patients; this the metastasis to host tissue; metastatic lesions in the liver or could potentially be beneficial in making decisions regarding bone can result in elevations in these enzymes secondary to patient management with implications for treatment, as well perturbations in the normal cellular physiology of hepatocytes as for surveillance following therapy. or osteocytes. Overall, these numbers are small and it would be useful to It was our purpose to determine how useful this practice is by determine if this pattern is consistent in a larger cohort. looking at a cohort of patients with RCC to identify how often Nonetheless, these findings raise questions regarding the the presence of an elevated AST, ALT, or ALP actually identified utility of obtaining the comprehensive metabolic panel in a patient with a metastatic lesion to the liver or bone. In the patients with RCC for the purposes of screening for metastatic cohort of patients that was evaluated, no patients with an disease. Our data suggest that the practice is not very useful for elevated AST or ALT were found to have metastasis to the liver; identifying metastasis to the liver or bone, but may be useful conversely, 5 patients were identified who had metastasis to in identifying lesions in the lungs. If a patient with a renal mass the liver but had no evidence of AST or ALT elevation. Similarly, consistent with RCC has a negative chest X-ray and an elevated none of the 5 patients identified with bone metastases had ALP, in the absence of bone pain to suggest bone metastasis, elevations in ALP. This raises the question, in patients presenting or evidence to suggest liver metastasis, closer pulmonary with liver or bone metastases, why were there no aberrations evaluation could be considered. seen in these enzymes? One possible explanation could be the burden of the metastasis was not significant enough to Our study is not without limitations, including its retrospective disrupt the host tissue to produce changes in the levels of these design, as well as a small sample size (including only 19 patients enzymes at a clinically detectable level. with metastatic disease), which limits its statistical power. In addition, not all patients received a bone scan, as a result An additionally interesting finding was that 3 of the 9 patients of our general practice to only pursue this in the setting of with lung metastases had isolated elevations in ALP. This patient-reported bone pain. Nonetheless, it appears that these finding of elevated ALP in the presence of lung metastases traditional markers are unreliable indicators of metastatic RCC. should not be unexpected given that pulmonary tissue is known to express ALP [5]. Whether these elevations in ALP definitively Conclusion represented perturbation of the pulmonary tissue by the presence of metastasis or an unrelated coincidental elevation in Common laboratory values obtained as part of the evaluation ALP secondary to some other tissue that expresses this enzyme of patients presenting with RCC are not routinely elevated in is unclear and would not be discernable without the use of patients with metastatic disease to the liver and bone. ALP is electrophoresis to determine which tissue-specific isoenzyme elevated in patients with lung metastasis in some cases. This will is elevated. However, it should be noted that each of these 3 require further investigation to determine if this relationship is patients with lung metastases were diagnosed with the chest causative or correlative. X-ray that is routinely ordered as part of the initial evaluation. REFERENCES The etiology of the elevated enzymes in the remaining 58 patients is unknown, but it is possible that some were secondary 1. Millán, JL. (2006). "Mammalian alkaline phosphatases: to Stauffer’s Syndrome, a paraneoplastic syndrome, which is from biology to applications in medicine." Wiley-VCH: 337.

2. Wein, A. J., L. R. Kavoussi, et al. (2011). Campbell-Walsh Urology, 10th ed. Elsevier-Saunders; Philadelphia, PA.

3. Catalano, C., F. Fraioli, et al. (2003). "High-resolution multidetector CT in the preoperative evaluation of patients with renal cell carcinoma." AJR Am J Roentgenol 180(5): 1271-1277. PubMed | CrossRef

4. Griffin, N., M. E. Gore, et al. (2007). "Imaging in metastatic renal cell carcinoma." AJR Am J Roentgenol 189(2): 360- 370. PubMed | CrossRef

5. Capelli, A., C. G. Cerutti, et al. (1997). "Identification of human pulmonary alkaline phosphatase isoenzymes." Am J Respir Crit Care Med 155(4): 1448-1452. PubMed | CrossRef

6. Stauffer, M. (1961). "Nephrogenic hepatosplenomegaly." Gastroenterology 40: 694.

7. Lee, S. E., S. S. Byun, et al. (2006). "Prognostic significance of common preoperative laboratory variables in clear cell renal cell carcinoma." BJU Int 98(6): 1228-1232. PubMed | CrossRef

8. Chuang, Y. C., A. T. Lin, et al. (1997). "Paraneoplastic elevation of serum alkaline phosphatase in renal cell carcinoma: incidence and implication on prognosis." J Urol 158(5): 1684-1687. PubMed

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.05 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Analysis of the Feasibility and Efficacy of Ambulatory/Day Care Percutaneous Nephrolithotomy: An Initial Experience

Adittya K. Sharma, M. Nagabhushan, G. N. Girish, A. J. Kamath, C. S. Ratkal, G. K. Venkatesh Submitted May 20, 2013 - Accepted for Publication June 16, 2013

Abstract

Purpose: Tubeless percutaneous nephrolithotomy (PCNL) is a well-accepted procedure for uncomplicated renal calculi. We prospectively evaluated the safety, feasibility, and efficacy of day care/ambulatory PCNL (totally tubeless, discharge within 24 hours) for selected patients for which only few case series have been reported. Materials and Methods: Total tubeless PCNL was planned in 40 easily accessible patients with uncomplicated renal calculi, with single infracostal punctures, normal intraoperative events, and acceptable postoperative parameters (visual analogue pain score, parenteral analgesic requirement, bleeding, urinary soakage, hemodynamic stability), allowing an early discharge within 24 hours. Parameters like pain score and analgesic requirement, any complications, and return date to normal work were evaluated at follow-up. Ultrasonography was performed after a week to document stone clearance. Results: Mean patient age was 38.6 years (22 to 62), stone size was 21.4 mm (15.4 to 30), and operating time was 72 minutes (42 to 106) without blood transfusion. Regional anesthesia was used in 13 cases while general anesthesia was used in the rest of the patients. Average pain score after 6 hours of surgery was 2.3 (1.8 to 3.6) with vitals in the normal range, and hospital stay was 12.5 hours (5.5 to 23.5). Six patients were excluded due to peri- and postoperative events (2: multiple punctures, 1: hematuria, 1: urine leak, 2: pain). This data was taken with the intention to treat the analysis with a successful application of study protocol in 34 (85%) of preoperatively selected cases. Out of 34 patients that qualified for a complete study protocol, 11 were discharged on the same day of surgery while the rest were discharged the next morning. Postoperative USG confirmed no residual calculus, and all patients had uneventful recoveries. Three patients had minor complications (mild hematuria/ urine leaks), which were managed conservatively. Conclusion: Our experience with ambulatory PCNL in properly selected cases suggests it as a feasible and effective option that can safely be offered to patients, providing uncomplicated surgery and favorable postoperative parameters.

Introduction of being noninvasive, day care later gives predictable stone clearance in a single sitting. Various modifications (supine Renal calculi pose major health issues in our society with PCNL, lateral PCNL) [2,3] in conventional prone PCNL have been percutaneous nephrolithotomy (PCNL) and shock wave tried to reduce operative time, postoperative morbidity, and lithotripsy (SWL) being standard treatments of choice. SWL is allows for early discharge. After the first report of outpatient the procedure of choice for most renal stones up to 2 cm except PCNL by Preminger et al. [4], in the past few years there have selected cases with unfavorable factors. PCNL is the choice for been various case series reporting day care/ambulatory PCNL calculi larger than 2 cm without any absolute contraindication with discharge on the same or following day within 24 hours to the procedure [1]. While the former gives the advantage [5-8]. We decided to evaluate the feasibility and efficacy of

KEYWORDS: Percutaneous nephrolithotomy, nephrolithiasis, kidney calculi CORRESPONDENCE: Adittya K. Sharma, MCh, Institute of Nephro-Urology, Victoria Hospital Campus, Bangalore, Karnataka, India ([email protected], [email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 44. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.03

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.03 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study ambulatory/day care PCNL defined as PCNL done for simple Table 1. Patient selection criteria. renal calculi and planned early discharge within 24 hours in an attempt speed early postoperative recovery and return to Inclusion criteria Easily accessible (within a 30-minute driving distance from institute) normalcy. No uncontrolled comorbidity (diabetes or hypertension) Materials and Methods ASA grade I/II Simple renal calculus cases requiring a With the approval of the institution review board, we selected single infracostal puncture 40 highly motivated patients based on preoperative selection Exclusion criteria Intraoperative complication (significant criteria (Table 1). Patients were educated regarding likely bleeding or pelvicalyceal injury) intraoperative difficulties and postoperative complications. Hemodynamic instability (tachycardia/ Patients were informed about likely complications (significant hypotension) pain, hematuria, urinary leaks) for which they must revisit the Postoperative pain score > 3 (on center immediately. Consent was taken with the explanation of analgesics), Hb < 11 gm% the investigative nature of the treatment protocol. Apart from Urinary leak, gross hematuria, or the preanesthetic workup, preoperative evaluation included signs of infection or incomplete stone clearance ultrasonography and intravenous urography (conventional or computed tomography). Patients were planned for total tubeless (no nephrostomy, no stent) PCNL with single-tract infracostal access. Instruments used were a 2-part initial puncture needle (18 G), Alken telescopic metal dilators, an Amplatz sheath (26 Fr), a Karl Storz nephroscope (22 Fr), Table 2. Patient characteristics. intracorporeal pneumolithotriptor, and alligator-type stone forceps. All patients were operated on by 2 senior urologists Variable Value experienced in PCNL. The procedure was performed in the No of Patients 34 prone position under fluoroscopic guidance after ureteric Sex male/female 23/11 catheter placement. Stone clearance was confirmed with intraoperative fluoroscopic and ultrasound (USG) imaging. Intraoperative events like hemodynamic stability, fluoroscopy Age Mean (range) 38.6 (22-62) time, degree of blood loss, and ease of stone clearance were Side right 15 noted. Postoperative parameters, which were taken into left 19 account, were the visual analogue scale (VAS; 1 to 10) for pain, Stone single 27 parenteral analgesic requirements, bleeding, urinary soakage, and hemodynamic stability. multiple 07 Stone size (mm) mean (Range) 22.4 (15.4-30) Postoperatively, patients were on injectable analgesics Radiopacity radiopaque/ 31/05 (diclofenac sodium: 75 mg/8 to 12 hourly; tramadol: 50 mg, radiolucent SOS). As per our study protocol, all patients had planned Preoperative Hb mean (SD) 13.6 (1.24) discharge from the facility within 24 hours of surgery. At follow-up, parameters evaluated were pain score and analgesic requirements, any complication (Clavien Dindo system) [9], and day returning to normal work. An X-ray check-up of the chest and kidney-ureter-bladder (KUB) work-up were done before discharge. Follow-up ultrasonography was performed on day 7 choice. Out of 40 preoperatively selected cases, 6 patients to confirm clearance of any residual fragments. were excluded from final analysis due to intraoperative and postoperative events. Two patients required a second puncture Results (stone size: 2.8 and 3 cm). Postoperatively, 1 had significant hematuria, another had a urinary leak from the puncture Preoperative patient characteristics are mentioned in Table 2. site, and 2 complained of significant postoperative difficulty All patients had preoperative sterile urine cultures. A total of 13 (mean VAS: 5.5; duration of surgery: 98 and 106 min). All the patients were operated under regional anesthesia while others complications were managed conservatively but prolonged were under general anesthesia. Anesthesia choice was decided the hospital stay beyond 24 hours, limiting the data of these 6 by the anesthetist on a case-to-case basis, which also included patients, including complete intention-to-treat analysis. factors like expected surgical difficulty and the patient’s

Table 3. Intra- and postoperative parameters. Figure 1. Preoperative and postoperative KUB confirming stone clearance. Intraoperative Postoperative operative time: 72 min Hb drop: 1.4 gm% (0.8-2.2) (42-106) fluoroscopy: 5.2 min (3-8.5) VAS at 6 hours: 2.3 (1.8-3.6) stone clearance: 100% hospitalization: 12.5 hours (4.5-23.5)

In the remaining 34 patients who could complete the study protocol, average pain score after 6 hours of surgery was 2.3 (1.8 to 3.6), with vitals in the normal range. (Table 3). Eleven cases were discharged on the same day of surgery (within 6 hours) while the rest were discharged the next morning. Postoperative X-ray KUB and USG confirmed no residual calculi (Figure 1). Three patients developed complications after initiation of activity, which were not present at the time of discharge. Two corresponds to a clamped nephrostomy tube [20]. There are patients presented with hematuria (mild) and 1 with a urinary also a few case series on totally tubeless and stentless PCNL in leak. All these complications were Clavien-Dindo grade I and properly selected patients [21]. were managed conservatively. Krambeck et al. reported long-term outcomes following PCNL Discussion mentioned at 19 years of follow-up. The stone recurrences were less frequent following PCNL compared to SWL (36.8% vs. 53.5%) The pros and cons of PCNL versus SWL have often been [22]. PCNL was not associated with the development of adverse highlighted when one discusses the management of renal medical events (new onset renal failure, diabetes mellitus, and stones. An oft-quoted point is that PCNL entails a prolonged hypertension) compared with SWL and conservatively managed hospital stay whereas SWL sessions are day-surgical in nature. stone cases. However, PCNL has a superior stone clearance rate compared to SWL, especially for lower pole stones [10]. In uncomplicated With increasing experience with PCNL, the safety and efficacy of PCNL, where there is no significant extravasation, significant PCNL have significantly increased. Our experience with limited bleeding, or any need for a second nephroscopy, the placement but properly selected patients has shown that such cases can be of the nephrostomy tube may not be necessary (tubeless PCNL) discharged conveniently within 24 hours of surgery or even the [11-14]. same evening on a day care basis. Surely this approach requires vigilant and strict follow-up; hence, only patients within a After > 30 years of worldwide experience, PCNL remains convenient distance from the facility have been selected so a milestone technique in the field of endourology, with a that they can report easily for follow-up, as well as for any high success rate and acceptably low percentage of major unexpected event after discharge. complications [15]. Unlike retrograde intrarenal surgery (RIRS) or SWL, the success of PCNL for the treatment of lower With the assessment of intention-to-treat analysis, our calyceal calculi does not depend on anatomic factors [16] or ambulatory protocol could be successfully applied to 85% of stone size [17,18]. Routine placement of the nephrostomy preoperatively selected patients. All patients who completed the tube after uncomplicated PCNL is being seriously questioned. protocol had unremarkable intraoperative and postoperative Since its initial description in 1997, there have been increased parameters and complete stone clearance with < 9% requiring reports of tubeless PCNL in the literature where percutaneous unplanned revisits for minor complications, which were nephrostomy is replaced by indwelling ureteral stents or a managed conservatively. Our study has limitations of only 34 ureteric catheter at the end of an uncomplicated PCNL [14,19]. cases, and since it is an initial experience, only uncomplicated It is based on the principle that simple closure of the tract with simple renal calculi were selected. Even after strict patient a dressing or parietal suture creates a closed retroperitoneal selection, the chances of complication are still there, as 15% compartment, which is ideal for achieving self-tamponade. This of preoperatively selected patients were excluded due to intra- and postoperative events. Luckily, none of our patients had

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.03 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study any major complications, yet nothing can replace the surgeon’s 10. Chong, W. L., S. Murali, et al. (2002). "Day care percutaneous experience and careful patient selection. renal surgery--is this viable?" Med J Malaysia 57(1): 108- 110. PubMed Conclusion 11. Bellman, G. C., R. Davidoff, et al. (1997). "Tubeless Ambulatory PCNL, in selected patients, is an advantage for percutaneous renal surgery." J Urol 157(5): 1578-1582. complete and predictable stone clearance with an early return PubMed | CrossRef to normal activity. Surely with experience the spectrum can be widened to incorporate more patients. Therefore, patient 12. Lojanapiwat, B., S. Soonthornphan, et al. (2001). "Tubeless compliance and understanding about the procedure and percutaneous nephrolithotomy in selected patients." J unwanted events are highly desirable, and no one but the Endourol 15(7): 711-713. PubMed | CrossRef patient has to take responsibility for the final informed decision for availing ambulatory protocol. 13. Goh, M. and J. S. Wolf, Jr. (1999). "Almost totally tubeless percutaneous nephrolithotomy: further evolution of the REFERENCES technique." J Endourol 13(3): 177-180. PubMed | CrossRef

1. Türk C., T. Knoll, et al. (2013). "Guidelines on Urolithiasis. 14. Shah, H. N., V. B. Kausik, et al. (2005). "Tubeless EAU Guidelines: 46-48. percutaneous nephrolithotomy: a prospective feasibility study and review of previous reports." BJU Int 96(6): 879- 2. Kumar, P., C. Bach, et al. (2012). "Supine percutaneous 883. PubMed | CrossRef nephrolithotomy (PCNL): 'in vogue' but in which position?" BJU Int 110(11 Pt C): E1018-1021. PubMed | CrossRef 15. McDougall, E. M. (2012). "Percutaneous approaches to the upper urinary tract." In: P. C. Walsh, et al., eds. Campbell's 3. El-Husseiny, T., K. Moraitis, et al. (2009). "Percutaneous Urology, 10th ed. Elsevier-Saunders; Philadelphia, PA: endourologic procedures in high-risk patients in the lateral 3320–3360. decubitus position under regional anesthesia." J Endourol 23(10): 1603-1606. PubMed | CrossRef 16. Elbahnasy, A. M., R. V. Clayman, et al. (1998). "Lower- pole caliceal stone clearance after shockwave lithotripsy, 4. Preminger, G. M., R. V. Clayman, et al. (1986). "Outpatient percutaneous nephrolithotomy, and flexible ureteroscopy: percutaneous nephrostolithotomy." J Urol 136(2): 355-357. impact of radiographic spatial anatomy." J Endourol 12(2): PubMed 113-119. PubMed | CrossRef

5. Singh, I., A. Kumar, et al. (2005). ""Ambulatory PCNL" 17. Murphy, D. P. and S. B. Streem. (2001). "Lower pole renal (tubeless PCNL under regional anesthesia) -- a preliminary calculi: When and how to treat." Braz J Urol 27: 3-9. report of 10 cases." Int Urol Nephrol 37(1): 35-37. PubMed | CrossRef 18. Lingeman, J. E., Y. I. Siegel, et al. (1994). "Management of lower pole nephrolithiasis: a critical analysis." J Urol 151(3): 6. Beiko, D., M. Samant, et al. (2009). "Totally tubeless 663-667. PubMed outpatient percutaneous nephrolithotomy: initial case report." Adv Urol: 295825. PubMed | CrossRef 19. Rana, A. M., J. P. Bhojwani, et al. (2008). "Tubeless PCNL with patient in supine position: procedure for all seasons?- 7. Beiko, D. and L. Lee (2010). "Outpatient tubeless -with comprehensive technique." Urology 71(4): 581-585. percutaneous nephrolithotomy: the initial case series." Can PubMed | CrossRef Urol Assoc J 4(4): E86-90. PubMed 20. Sofer, M., A. Beri, et al. (2007). "Extending the application 8. Shahrour, W. and S. Andonian (2010). "Ambulatory of tubeless percutaneous nephrolithotomy." Urology 70(3): percutaneous nephrolithotomy: initial series." Urology 412-416; discussion 416-417. PubMed | CrossRef 76(6): 1288-1292. PubMed | CrossRef 21. Crook, T. J., C. R. Lockyer, et al. (2008). "Totally tubeless 9. Dindo, D., N. Demartines, et al. (2004). "Classification of percutaneous nephrolithotomy." J Endourol 22(2): 267- surgical complications: a new proposal with evaluation in a 271. PubMed | CrossRef cohort of 6336 patients and results of a survey." Ann Surg 240(2): 205-213. PubMed | CrossRef

22. Krambeck, A. E., A. J. LeRoy, et al. (2008). "Long-term outcomes of percutaneous nephrolithotomy compared to shock wave lithotripsy and conservative management." J Urol 179(6): 2233-2237. PubMed | CrossRef

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.03 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® The Challenge of Difficult Catheterization in Men: A Novel Technique and Review of the Literature

Mario Gardi, Giulio Massimo Balta, Marcello Repele, Nicola Zanovello, Giovanni Betto, Simonetta Fracalanza, Wanni Battanello, Bruno Santoni, Silvia Secco, Andrea Agostini, Massimo Dal Bianco Submitted June 1, 2013 - Accepted for Publication July 31, 2013 Abstract

Male urethral catheterization can be difficult and is still a familiar problem for urologists. A laborious male urethral catheterization is often consequent to the presence of a bulky prostate due to benign prostatic enlargement, a condition intimately related to aging with an increasing prevalence in elderly people. The task of passing a urethral catheter in this atypical condition often leads to repeated and unsuccessful attempts, which can cause the patient distress, and are often related to a wide range of complications, sometimes leading to medico-legal lawsuits.

We describe a simple and safe technique only requiring equipment readily available in every urology department. It facilitates the chances of an atraumatic and successful catheter insertion in men suffering from different pathologic or anatomic conditions when a primary attempt of simple transurethral catheterization fails. The performance of the technique was tested in 76 patients who required bladder catheterization by a urologic consultant because of failed primary attempts. Difficulties were attributable to past transurethral resection of the prostate in 10 patients, past open radical retropubic prostatectomy in 7, and benign prostate enlargement in 59. Successful catheterization was obtained in 65 patients, 5 patients were otherwise catheterized by a rigid catheter, and 6 required a suprapubic catheter or flexible cystoscopy. Complications comprised self-limiting urethral bleeding in 12 patients, urinary tract infection in 4, and false passage in 2.

The technique is well tolerated and increases the likelihood of successful primary urethral catheterization in this set of patients; moreover, a hospital admission that is needed in case of placing a suprapubic catheter is not required.

introduction a condition intimately related to aging with an increased prevalence in elderly people [1]. LMale bladder transurethral catheterization can be difficult and is still a familiar problem for urologists. It can be a challenge The task of passing a urethral catheter in this atypical condition involving a urethral stricture, false passages as a result of often falls to the more junior and inexperienced members previous unfruitful attempts at catheterization, prostate cancer, of staff, and may represent a potential cause for a lawsuit bladder neck contractures following transurethral resection of [2]. Repeated, rough, and unsuccessful attempts can cause the prostate, and obliterated anastomosis following a radical the patient distress and are often related to a wide range of prostatectomy. More often a laborious catheterization may be complications, such as urethral damage, including significant due to a bulky prostate in case of benign prostatic enlargement, bleeding (e.g., in men assuming oral anticoagulants) and the

KEYWORDS: Difficult catheterization, bulky prostate, prostate enlargement, complication, malpractice CORRESPONDENCE: Mario Gardi, MD, PhD, Urology Unit, Department of Surgery, Ospedale Sant’Antonio, Building G, Via Facciolati, 71, Padova, Italy ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 53. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.12

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.12 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study late onset of urethral strictures [3], and more serious morbid Figure 1. Flow chart adopted to manage vesical conditions such as sepsis, rectal perforation, and Fournier's catheterization. *Distance from the external urethral gangrene. We describe a simple and safe technique that meatum; Ch = Charriere unit (1/3 mm). TURP = trans- facilitates the chances of atraumatic and successful catheter urethral resection of prostate; RRP = radical retropubic insertion in men suffering of sub-stenotic vesicourethral prostatectomy. anastomosis, bladder neck contractures following transurethral resection of the prostate, or bulky prostate due to benign prostatic enlargement or cancer.

METHODS

When catheter placement is required to resolve acute retention or for clinical monitoring, the first step is to focalize on past medical history and physical examination. It's important to know whether a patient underwent prior urological surgeries (such as radical prostatectomy or urethroplasty), endoscopic procedures (such as transurethral prostate resection or cystoscopy), previous urethral stenosis or voiding dysfunctions, assuming medical therapy for benign prostatic hyperplasia or prostate cancer, or reported difficult catheterization in the past. To the same extent, information deriving from previous attempts at catheterization are important. This includes the type and size of the catheter used, the level of a perceived stop during catheter advancement, inflation of the catheter balloon, possible pain by the patient indicating urethral trauma due to expansion of the balloon elsewhere than the bladder, urethral bleeding, the number of attempts at catheterization, and personnel involved (nurses, general practitioner) [3]. Physical examination can show signs of urethral trauma (blood at the meatus) or possible causes of difficult catheterization such as anasarca, phimosis, micro penis, meatal stenosis, penile oedema, prostate cancer, or prostate enlargement. To manage all these possible scenarios, we adopted an internal flow chart to allow the discrimination between different underlying conditions, suggesting different possible solutions for vesical catheterization (Figure 1).

Catheterization is an aseptic skill that requires appropriate training and material. The present technique only requires equipment readily available in every urology department. Aside from the normal material used in a classical catheterization procedure, our technique in particular involves the use of a common Foley catheter (16 Fr) in flexible latex supplied with (Figure 2c) and then clamp with the Klemmer the proximal an autostatic inflatable balloon at the internal tip. We use extremity of the Foley, so fixing the Foley catheter and the an additional ureteral catheter (4 Fr) formed of an external ureteral catheter contained within (Figure 2d). Using gauze, removable plastic sheet with one blind tip (see arrow in Figure fold the Foley tip reinforced by the inner ureteral catheter to 2b), containing a straight cylindrical metal stylet coming give it the appearance of a Mercier catheter extremity (tip the out from the other tip (see arrow in Figure 2b) and a plastic extremity with an angle of 45 degrees with respect to the major Klemmer and two 5 mL tubes of lubricant gel (Figure 2a). axis of the catheter). Because of the internal partially metallic mandrel, the given shape will be maintained after the force is The first step consists of assembling the device in a sterile applied (Figure 2f and Figure 2g). The Klemmer is now oriented manner as follows: Insert the lubricant gel into the single to maintain the same direction of the folded tip so that the lumen of the Foley catheter until the gel itself comes out from tip orientation is known every time the catheter is inserted the tip holes. Insert the blind tip of the ureteral catheter into (Figure 2f and Figure 2g). The preparative phase to subsequent the lumen of the Foley catheter until it reaches the Foley tip catheterization is completed.

Figure 2. The schematic passages of our technique. a) the distribution of lubricant in the direction of the posterior Material used to prepare our self-assembled catheter. b) urethra. Wait a few minutes for the anesthetic to work. Next, The catheter is formed of an external removable plastic wearing a second pair of sterile gloves, retract the foreskin, and sheet with one blind tip (thick black arrow) containing hold the penis upright in the non-dominant hand at about 60 a straight cylindrical metal stylet coming out from the to 70 degrees of inclination, supporting with gauze wrapped other tip (thin black arrow). c) After the lubricant gel is around it. Just before you begin the catheterization, suggest introduced, insert the blind tip until it reaches the Foley that the patient take a few more slow deep breaths. This tip. d) Clamp with the Klemmer. e) Using gauze, fold the facilitates the relaxation of the urogenital diaphragm and avoids tip to give it the appearance of a Mercier catheter. f) contraction of the external voluntary sphincter due to fear or Because of the internal mandrel the given folded shape muscular tension. This passage is useful when attempting to will be maintained after force is applied. g) The Klemmer overrun the posterior urethra to reach the bladder. Grasp the is now oriented to maintain the same direction of the catheter near the tip and insert it slowly, eventually by using folded tip. h) After insertion, release the Klemmer and additional sterile gauze to transfer to a pushing movement of extract the ureteral catheter. the catheter. Continue to insert the catheter until its bifurcation. After complete insertion, release the Klemmer and extract the ureteral catheter (sheet and metal stylet together). The Foley catheter recovers its original straight tip shape (Figure 2h). Usually, urine doesn't come out immediately because of the gel obstructing the tip of the catheter. By palpating the bladder you will force urine to open the catheter tip holes. Just in case, aspiration by a syringe can help you with this purpose. Only when there is evidence of correct placement of the catheter into the bladder, you can inflate the Foley balloon, retract the catheter on the bladder neck, and cover the glans penis with its prepuce when present.

RESULTS

We tested the described technique in 76 male patients in our hospital requiring transurethral bladder catheterization by a urologist consultant because of a primary failed attempt. Indication of bladder drainage was, in 51 cases, acute retention of urine; other indications were pre-/intraoperative needs in 16 cases and clinical monitoring in 9 cases. The median age was 56.3 (range: 48 to 82), and in all patients there was at least 1 attempt of bladder transurethral catheterization (mean: 1.6) by a non-urologic physician. In most of these patients urological anamnesis was uneventful, thus difficult catheterization was attributable to a bulky prostate due to benign prostate enlargement. Other patients had a history of surgical interventions of the genitourinary tract; 10 patients in particular reported transurethral resection of the prostate and 7 patients reported open radical retropubic prostatectomy. In all cases the difficulty to pass a common Foley catheter (16 Fr) was verified by the urologic consultant. In 65 cases the described technique led to successful passage of the catheter into the bladder, while in 11 cases it was unfruitful. The subsequent management in the latter cases involved the use of a Mercier catheter with a tip hole allowing the passage of a ureteral catheter or a guide After application of common cleaning of the external male wire. This maneuver solved the problem in 5 patients, with genitalia, insert around 10 mL of local anesthetic gel (Lidocaine concomitant pressure exerted by an assistant in 2 out of 5 cases. hydrochloride, 2.5%) into the urethra and then hold the glans For 6 patients it was also unfruitful, and they underwent the penis firmly to prevent the gel being released. Gently press the successful placement of a suprapubic cystostomy (4 patients) or underside of the penile shaft in a downward direction to favor a flexible cystoscopy (2 patients). The technique was generally

Table 1. Clinical features of included patients and their role of junior and inexperienced members of staff, potentially results. representing a source of medico-legal lawsuits for a urologist [4-9], especially when rough and unsuccessful attempts cause General Data the patient distress and complications [2]. In the last few years, - age (years) 56.3 (48-82) malpractice claims burst up to impressive figures, and almost every physician experienced/will experience some kind of claim, - previous attempts (number) 1.6 (1-3) at times, in a formal legal setting [10-12], as demonstrated Urological Anamnesis N (%) by the expanding role of legal medicine and the growth of - past retropubic open radical 7 (9) guidelines in the field [13-15]. prostatectomy (N) - past transurethral resection of 10 (13) In this scenario, we described a simple technique for difficult, prostate (N) male, bladder transurethral catheterization, reporting its clinical outcome as a contribution to the body of evidence on - uneventful (N) 59 (78) this issue [16]. The technique is suitable for all male patients in Indication for catheterization whom there is no contraindication to urethral catheterization, - acute urinary retention 51 (67) and it can be performed at the bedside or during office activity, - pre/intra-operative needs (non- 16 (21) ensuring safety at all times. The technique does not add urological surgery) morbidity compared to simple catheterization and increases - clinical monitoring (hospital 9 (12) the likelihood of successful primary urethral catheterization in setting) the case of acute retention of urine or the need to monitor diuresis in clinical settings. Moreover, it doesn’t require hospital Outcomes admission, as in the case of placement of a suprapubic catheter. - successful 65 (85,5) The required experience to place this self-assembled catheter is - unfruitful 11 (14,5)* the same involved for the use of Mercier catheters, and we did Complications not observe a different incidence of complications due to the adoption of this composed device. - urethral bleeding (self-limited) 12 (16) - urinary tract infections 4 (5) Different methods have been described since 1979 in order to - false passage 2 (2,5) overcome difficult transurethral catheterization in different clinical situations (Table 2). Many of them involve the use of - rectal injury 0 (0) *Subsequent adopted measures were the use of a Mercier a cystoscope, which led to the placement of a guide wire into catheter with a tip hole allowing the passage of a ureteral the bladder after passing the stricture. Nowadays the flexible catheter or guide wire (5), placement of a suprapubic cystoscope is readily available in urology departments, but it cystostomy (4), or flexible cystoscopy (2). is rarely available in non-urological departments, such as the emergency room or intensive care departments. Moreover, it requires connection to a light source and a water flux, and its use often implies the presence of an assistant. These aspects limit the use of any cystoscope-based technique at the bedside. The most popular method to manage difficult catheterization well tolerated by all patients and no major complications is the glide-wire technique, first described by Freid and Smith occurred. We observed urethral bleeding in 12 patients, which [10]. A hydrophilic-coated glide wire is introduced through stopped by itself in less than 30 minutes in all of these patients. the urethra and advanced with gentle, steady pressure until Two patients developed signs and symptoms of urinary the obstruction is overcome and the wire reaches the bladder. tract infection requiring the administration of antibiotics. After that, an open-ended ureteral catheter is passed over the Finally, in the 2 patients who underwent flexible cystoscopy, wire, the guide wire is substituted with a Teflon-coated guide a false passage was documented. Table 1 summarizes patient wire, and finally a Graham catheter is placed over the ureteral characteristics and results. catheter guide wire, or alternatively the urethra is dilated until DISCUSSION 18 Fr to pass a 16 Fr Foley catheter. The technique was further revisited by others, introducing minor modifications such as the use of a Foley catheter with a cut tip to be passed over the The task of passing a urethral catheter often involves the active

Table 2. Literature review on the issue.

Year Author Pts Clinical setting Maneuvers and tips

Vaginal speculum to visualize the glans and long forceps to advance the 1979 Walden [17] 3 Patients affected by anasarca catheter

Abundant jelly, Coude-type catheter 16-18 Ch, urethrography, urethroscopy, and then filiforms under direct vision with (a) a council tip over a stylet 1985 Jordan et al. [18] - Intraoperative consult attached to the filiform or (b) use of a balloon urethral dilatator or suprapubic catheterization

Flexible cystoscope to bypass the stop using a guide wire, ureteral catheter Difficult catheterization in patients without 1989 Krikler. [19] - placed following the guide wire, Foley with a cut tip is placed following the false passages or diverticula ureteral catheter

False channels, undermined bladder neck Sheath placed over a cystoscope reaching the bladder, remove the cystoscope, 1992 Lowe et al. [20] 20 after TURP, early loss of catheter after RRP and pass the Foley within the sheath.

Abundant jelly, a Coude-type catheter 20-24 Ch for BPH, and 14-16 Ch for 1993 Cancio et al. [21] - Difficult catheterization strictures, eventually using perineal pressure.

Unfruitful previous attempts in patients with Flexible cystoscope to visualize the obstruction, that is bypassed by a guide 1994 Beaghler et al. [22] 54 reported weak urinary stream and urinary wire, sequential dilatation (Nottingham dilatators) to allow the passage of a retention Council-type catheter over the guide wire

Difficult catheterization in patients with Flexible cystoscope to bypass the stop and reach the bladder, a guide wire is 1995 Blitz [23] 8 previous endoscopic prostate or urethral then inserted through the cystoscope, the cystoscope is removed and a Foley procedures with a cut tip is placed following the guide wire

Guide wire is inserted to reach the bladder, ureteral catheter over it, substitution of the guide wire with a Teflon-coated guide wire. After this: Unfruitful catheterization with cystoscopy not 1996 Freid et al. [24] 20 (a) Graham catheter is passed following the ureteral catheter containing the available Teflon guide wire, or (b) dilatation to 16-18 Ch and then pass a Council-type catheter.

Unfruitful catheterization (single attempt) in Foley catheter is placed through the urethra by simultaneously instillation of 1998 Harkin et al. [25] 30 absence of major urethral trauma saline solution by a catheter tip syringe attached to the Foley.

Short rigid urethroscope passed through a modified Foley catheter (22 Ch). Undermined bladder trigone after TURP or 1998 Rozanski et al. [26] 2 This combined system reaches the bladder under vision. The urethroscope is TUIP then removed.

Guide wire reaches the bladder, a Foley (6 Ch) with a cut tip is advanced over 2000 Lachat et al. [27] 21 Intraoperative consult the wire.

Hydrophilic guide wire is advanced into the bladder, and then: (a) a Foley Unfruitful initial attempts with a Foley with a cut tip is advanced over the guide, or (b) a ureteral catheter is placed 2004 Zammit et al. [28] - catheter 16 Ch over the guide, with subsequent dilatation and placing of a Foley with a cut tip (12 Ch).

Athanasopoulos et 2005 - Urethral strictures Hydrophilic guide wire followed by a 14-16 Ch ureteric access sheath. al. [29]

Acute retention after unfruitful attempts for Hydrophilic catheter (12-18 Ch), guide wire passed through it and its 2007 Mistry et al. [30] 30 catheterization by using 12-18 Ch urethral substitution with a Council-type catheter. catheters

Flexible cystoscope to visualize the obstruction that is bypassed by a guide 2008 Chelladurai et al. [31] - Urinary retention due to ureteral stricture wire; sequential dilatation over the guide to allow the passage of a catheter on it

Flexible-tip hydrophilic glide wire is placed to reach the bladder under Athanasopoulos et fluoroscopic control and a ureteral access sheath with its trocar (14-16 Ch) 2009 10 Difficult catheterization for urethral stricture al. [32] follows the guide under fluoroscopy. Upon removing the trocar, a Foley (12 Ch) is then placed and the sheath extracted.

A stiff guide wire is placed with its floppy end within a Foley and proximally 2009 Liss et al. [33] 6 Difficult catheterization clamped to the catheter to obtain a single system. Pts = Patients; BPH = Benign Prostatic Hyperplasia; Ch = Charriere unit (1/3 mm), TURP = transurethral resection of prostate; TUIP = trans-urethral incision of prostate; RRP = radical retropubic prostatectomy.

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.12 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® wire [13,14], the use of an ureteric access sheet to be passed by patients, increasing the overall likelihood of successful over the wire [15,18], or the use of a hydrophilic non-autostatic primary urethral catheterization without the need for hospital small catheter in order to place the wire into the bladder admission. [16]. In general, authors using the guide wire technique have reported high success rates. Limitations are that 2 or more References passages are needed compared to our methods, and the fact that it is never possible to check the vesical position of the 1. Chute, C. G., L. A. Panser, et al. (1993). "The prevalence wire, it could be a problem in case of false passage. Another of prostatism: a population-based survey of urinary proposed technique is the so-called “Liss maneuver” [19]. A symptoms." J Urol 150(1): 85-89. PubMed 0.035-inch super stiff guide wire was placed floppy end first down a 18 Fr Foley catheter lumen; the guide wire was then 2. Boscolo-Berto, R., D. I. Raduazzo, et al. (2012). "Urethral clamped proximally to the body of the catheter at its point of catheterization in men with artificial urinary sphincter: exit. The body of the wire increased the catheter body stiffness clinical and legal implications." Urol J 9(3): 611-613. while the tip of the catheter, holding the floppy end of the PubMed wire, showed no significant increase in stiffness. This method is similar in the concept to the one described in this article. We 3. Villanueva, C. and G. P. Hemstreet, 3rd (2008). "Difficult believe, however, that giving a Mercier-like shape to the tip male urethral catheterization: a review of different of the catheter provides more chances to pass the catheter, approaches." Int Braz J Urol 34(4): 401-411; discussion 412. especially in the case of a bulky prostate due to benign prostate PubMed enlargement, because of the anatomical fitting. 4. Boscolo-Berto, R., M. Iafrate, et al. (2010). "Forensic The advantage of using the described technique is the chance implications in self-insertion of urethral foreign bodies." to easily position a flexible latex catheter supplied with an Can J Urol 17(1): 5026-5027. PubMed autostatic inflatable balloon in a single passage by temporarily adapting its tip and reducing its deformability. In this way 5. Boscolo-Berto, R., C. Lamon C, et al. (2010). "A major we are not obliged to substitute a Mercier-type catheter by clinical event following transperineal prostate biopsy: An introduction of a guide to allow subsequent substitution unexpected duodenal perforation." Urotoday Int J 3(2): with a Foley catheter modified with a tip hole, or a council 1-5. catheter [3]. By these tricks, we can afford the task of a difficult catheterization in male patients with a bulky prostate, abating 6. Boscolo-Berto, R., D. I. Raduazzo, et al. (2011). "Aggressive the number of unfruitful attempts and unnecessary passages non-Hodgkin's lymphoma mimicking unilateral transitional of other catheters and guides, and the resulting likelihood of cell carcinoma of renal pelvis. The risk of making a complications derived from the repeated procedures. diagnostic mistake." Arch Ital Urol Androl 83(3): 163-165. PubMed The armed Foley technique here described was fruitful in a 7. Boscolo-Berto, R., G. Viel, et al. (2011). "Determinism and defined clinical situation, such us a bulky prostate, bladder liabilities in a complicated transrectal prostate biopsy: what neck stricture from past transurethral resection of the prostate, is what." Urologia 78(3): 176-179. PubMed | CrossRef and stenosis of the vesicourethral anastomosis after radical prostatectomy. As other methods, it seems to be more suitable 8. Boscolo-Berto, R., G. Viel, et al. (2011). "Giant scrotal to manage difficult catheterization in different situations, such lymphedema as unique onset sign of muscle-invasive as strictures of the anterior urethra. We propose an algorithm bladder cancer. The risk of a misdiagnosis." Arch Ital Urol in order to manage difficult transurethral catheterizations, Androl 83(2): 95-98. PubMed taking into account this novel method.

9. Boscolo-Berto, R., G. Viel, et al. (2012). "Male infertility CONCLUSION after transpelvic gunshot wound injury: a case of clinical and forensic relevance." Urol J 9(4): 714-717. PubMed We described a simple and safe technique to allow catheter insertion in men suffering with different pathologic or anatomic 10. Boscolo-Berto, R., G. Viel, et al. (2012). "Journals publishing conditions when a primary attempt at simple transurethral bio-medicolegal research in Europe." Int J Legal Med catheterization fails. The technique is safe and well tolerated 126(1): 129-137. PubMed | CrossRef

11. Ferrara, S. D., T. Bajanowski, et al. (2011). "Bio-medicolegal 23. Blitz, B. F. (1995). "A simple method using hydrophilic guide scientific research in Europe: a comprehensive bibliometric wires for the difficult urethral catheterization." Urology overview." Int J Legal Med 125(3): 393-402. PubMed | 46(1): 99-100. PubMed | CrossRef CrossRef 24. Freid, R. M. and A. D. Smith (1996). "The Glidewire 12. Viel, G., R. Boscolo-Berto, et al. (2011). "Bio-medicolegal technique for overcoming urethral obstruction." J Urol scientific research in Europe. A country-based analysis." Int 156(1): 164-165. PubMed J Legal Med 125(5): 717-725. PubMed | CrossRef 25. Harkin, D. W., M. Hawe, et al. (1998). "A novel technique 13. Boscolo-Berto, R. (2010). "Legal claims and bias in creating for difficult male urethral catheterization." Br J Urol 82(5): clinical practice guidelines: which step in which direction?" 752-753. PubMed Int J Urol 17(5): 498. PubMed | CrossRef 26. Rozanski, T. A., F. Salazar, et al. (1998). "Direct vision 14. Boscolo-Berto, R. (2011). "[Facing malpractice litigation: bladder catheterization using a short rigid ureteroscope." when the guideline fails to guide]." G Ital Nefrol 28(1): 12. Urology 51(5): 827-828. PubMed PubMed 27. Lachat, M. L., U. Moehrlen, et al. (2000). "The Seldinger 15. Ferrara, S. D., E. Baccino, et al. (2013). "Malpractice and technique for difficult transurethral catheterization: a medical liability. European Guidelines on Methods of gentle alternative to suprapubic puncture." Br J Surg Ascertainment and Criteria of Evaluation." Int J Legal Med 87(12): 1729-1730. PubMed | CrossRef 127(3): 545-557. PubMed | CrossRef 28. Zammit, P. A. and K. German (2004). "The difficult urethral 16. Boscolo-Berto, R. (2009). "[Clinical testing and evidence- catheterization: use of a hydrophilic guidewire." BJU Int based medicine: when the absence of evidence doesn't 93(6): 883-884. PubMed | CrossRef mean evidence of absence]." G Ital Nefrol 26(4): 417. PubMed 29. Athanassopoulos, A., E. N. Liatsikos, et al. (2005). "The difficult urethral catheterization: use of a hydrophilic 17. Walden, T. B. (1979). "Urethral catheterization in anasarca." guidewire." BJU Int 95(1): 192. PubMed | CrossRef Urology 13(1): 82. PubMed 30. Mistry, S., D. Goldfarb, et al. (2007). "Use of hydrophilic- 18. Jordan, G. H., B. H. Winslow, et al. (1985). "Intraoperative coated urethral catheters in management of acute urinary consultation for the urethra." Urol Clin North Am 12(3): retention." Urology 70(1): 25-27. PubMed | CrossRef 447-452. PubMed 31. Chelladurai, A. J., S. J. Srirangam, et al. (2008). "A novel 19. Krikler, S. J. (1989). "Flexible urethroscopy: use in difficult technique to aid urethral catheterisation in patients male catheterisation." Ann R Coll Surg Engl 71(1): 3. presenting with acute urinary retention due to urethral PubMed stricture disease." Ann R Coll Surg Engl 90(1): 77-78. PubMed 20. Lowe, M. A. and A. J. Defalco (1992). "New endourologic technique for catheter placement after TURP, 32. Athanasopoulos, A. and E. N. Liatsikos (2009). "The use prostatectomy, and difficult urethroscopy." Urology 40(5): of a ureteral access sheath for the urethral dilatation and 461-463. PubMed catheterization of difficult urethral strictures." Urol Int 83(3): 359-361. PubMed | CrossRef 21. Cancio, L. C., E. S. Sabanegh, Jr., et al. (1993). "Managing the Foley catheter." Am Fam Physician 48(5): 829-836. 33. Liss, M. A., S. Leifer, et al. (2009). "The Liss maneuver: PubMed a nonendoscopic technique for difficult Foley catheterization." J Endourol 23(8): 1227-1230. PubMed | 22. Beaghler, M., M. Grasso, 3rd, et al. (1994). "Inability to CrossRef pass a urethral catheter: the bedside role of the flexible cystoscope." Urology 44(2): 268-270. PubMed

Nandan R. Pujari, Sanjay B. Kulkarni Submitted March 21, 2013 - Accepted for Publication May 19, 2013

Abstract

Purpose: To analyze the utility of tamsulosin in patients with pelvic floor urethral distraction injuries (PFUDD) undergoing voiding cystourethrograms (VCUG) to assess the posterior urethra for length of the distraction defect. Materials and Methods: A prospective randomized analysis of 107 patients with PFUDD who underwent VCUG from August 2007 to September 2011 at our tertiary referral center for urethral stricture. Patients were randomized into 2 groups. A dosage of 0.4 mg of tamsulosin, a potent selective alpha-blocker, was administered orally to patients in the study group (N = 53) undergoing VCUG in whom the posterior urethra was not delineated due to competency of the bladder neck. A repeat voiding film was taken 10 to 12 hours after administering tamsulosin. The control group (N = 54) did not receive tamsulosin. Instead, they underwent further diagnostic techniques (magnetic resonance imaging [MRI], bougiogram, and antegrade cystourethroscopy) to assess the distraction defect. Results: Out of the 53 patients in the study group all 53 patients responded to oral tamsulosin. In the control group 32 patients required MRI, 20 patients required antegrade cystourethroscopy, and 2 patients required bougiograms. Conclusion: Tamsulosin effectively relaxed the bladder neck and allowed the delineation of the posterior urethra in patients of PFUDD with a competent bladder neck. This prevented the patients from undergoing further invasive diagnostic techniques (bougiogram and antegrade cystourethroscopy). Further prospective studies with a larger number of patients with multicenter experience will be required to validate these results.

Introduction in turn, is predictable according to the length of the defect. Therefore, preoperative estimation of the distraction defect Traumatic injuries to the urethra occur in approximately 10% length is extremely important to plan the extent of the surgery of patients who suffer pelvic fractures. In patients with pelvic preoperatively. floor urethral distraction injuries (PFUDD) the assessment of the distraction defect length can be difficult. We have described Purpose an easy method to overcome this commonly encountered problem of non-visualization of the posterior urethra during To analyze the utility of tamsulosin in patients with PFUDD voiding cystourethrograms (VCUG) by the use of tamsulosin, undergoing voiding VCUG to assess the posterior urethra for which is commonly used by all urologists. PFUDD is treated length of the distraction defect. surgically by the progressive perineal approach consisting of several well-defined surgical steps. The need for each step,

KEYWORDS: Tamsulosin, VCUG, distraction defect CORRESPONDENCE: Nandan R. Pujari, MS, DNB (Urology), Department of Urology, MGM Medical College, Mumbai, Maharashtra, India ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 42. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.01

Materials and Methods they underwent further diagnostic techniques (magnetic resonance imaging [MRI], bougiogram, and antegrade A prospective randomized analysis of 107 patients with PFUDD cystourethroscopy) to assess the distraction defect. The method underwent VCUG from August 2007 to September 2011 at of randomization was that alternate patients were allotted to our tertiary referral center for urethral stricture. Only patients the study and control groups. whose bladder neck did not open on VCUG were included in this study. Patients were randomized into 2 groups. A dosage Results of 0.4 mg of tamsulosin, a potent selective alpha-blocker, was administered to patients in the study group (N = 53) undergoing Out of the 53 patients in the study group all 53 patients VCUG in whom the posterior urethra was not delineated due responded to oral dosages of tamsulosin. In the control group to competency of the bladder neck. A repeat voiding film was 32 patients required MRI, 20 patients required antegrade taken 10 to 12 hours after the administration of tamsulosin. The cystourethroscopy, and 2 patients required bougiograms. Of method of analyzing the distraction defect in these patients the control group, 26 patients required anesthesia (22 patients was performed using simultaneous antegrade and retrograde for undergoing cystourethroscopy and 4 patients for MRI) urethrograms when the patient was asked to try and void in while none of the patients in the study group required it. Of order to delineate the posterior urethra. No additional contrast the control group, 2 patients developed urinary tract infection was used or diuretics given. (UTI) following cystourethroscopy while none developed UTI in the study group. The control group (N = 54) did not receive tamsulosin. Instead

Figure 3. Voiding cystourethrogram after tamsulosin. Figure 4. Opposing urethrogram.

The age of the patients in the study ranged from 10 to 47 years. an oral dose is 14 to 15 hours [3,4]. Tamsulosin is one of the All the patients were male. The site of urethral injury was the commonly prescribed drugs, and most of the current urologists posterior urethra in all patients. No serious side effects due to are well versed with the clinical usage of the drug. The side the orally administered drug were noticed in the study. effect profile of tamsulosin is excellent. Postural hypotension is rarely seen with this selective alpha-blocker. Failing this Discussion technique, alternate methods include simultaneous antegrade and retrograde bougiograms or antegrade cystourethroscopy An assessment of the gap between the 2 ends of the urethra suprapubically [5], which requires anesthesia. Overfilling the after posterior urethral injuries is important. In patients with a urinary bladder with contrast through a suprapubic catheter is competent bladder neck the prostatic urethra is not opacified also attempted in some centers. MRI has also been used but the with the contrast inserted through the suprapubic catheter cost of this investigation is markedly higher. The average cost (Figure 1). The bladder neck region is richly innervated with of tamsulosin tablets used in the study is $0.11 while the cost of alpha 1a autonomic receptors, which on stimulation increases an MRI is approximately $67.00 (P value = 0.00). bladder outlet resistance. Alpha-blockers relax the bladder neck and decrease bladder outlet resistance [1], allowing the Of the control group, 26 patients required anesthesia (22 contrast to enter the posterior urethra (Figure 3). Tamsulosin patients for undergoing cystourethroscopy and 4 patients for is an alpha antagonist with a modest degree of selectivity for MRI) while none of the patients in the study group required it the alpha 1a receptor [2]. The half-life of tamsulosin after (P value = 0.00). All 26 patients requiring anesthesia required

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.01 ISSN 1944-5792 (print), ISSN 1944-5784 (online) original study hospitalization. Of the control group, 2 patients developed UTI following cystourethroscopy while none developed UTI in the study group (P value = 0.499). The P value was calculated using the chi square test, and a P value < 0.05 was significant.

The purpose of all these investigative modalities was to assess the length of the distraction defect accurately. No study using tamsulosin for the purpose of assessing the length of distraction defect has been undertaken to date.

Conclusion

Tamsulosin effectively relaxes the bladder neck and allows the delineation of the posterior urethra in patients of PFUDD with a competent bladder neck. This prevents the patients from undergoing further invasive diagnostic techniques (bougiogram and antegrade cystourethroscopy). Further, prospective studies with a larger number of patients with multicenter experience will be required to validate these results.

REFERENCES

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2. Foglar, R., K. Shibata, et al. (1995). "Use of recombinant alpha 1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophy." Eur J Pharmacol 288(2): 201-207. PubMed | CrossRef

3. Matsushima, H., H. Kamimura, et al. (1999). "Plasma protein binding of tamsulosin hydrochloride in renal disease: role of alpha1-acid glycoprotein and possibility of binding interactions." Eur J Clin Pharmacol 55(6): 437-443. PubMed | CrossRef

4. Wolzt, M., V. Fabrizii, et al. (1998). "Pharmacokinetics of tamsulosin in subjects with normal and varying degrees of impaired renal function: an open-label single-dose and multiple-dose study." Eur J Clin Pharmacol 54(4): 367-373. PubMed | CrossRef

5. Hosseini, S. J., A. Kaviani, et al. (2006). "Diagnostic application of flexible cystoscope in pelvic fracture urethral distraction defects." Urol J 3(4): 204-207. PubMed

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.01 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Commentary on “Parental Attitudes Toward Fertility Preservation in Boys with Cancer: Context of Different Risk Levels of Infertility and Success Rates of Fertility Restoration,” Sadri-Ardekani et al. (2013). Fertil Steril 99: 796-802.

Thomas W. McLean, Hooman Sadri-Ardekani, Anthony Atala Submitted June 16, 2013 - Accepted for Publication July 21, 2013 Abstract

Cancer survival rates have increased dramatically in recent decades. Until better cancer therapies emerge, infertility will remain a common side effect of cancer therapy. Infertility therapies have likewise flourished in recent decades, but unfortunately the science of infertility has been relatively slow to infiltrate the oncology world. Parents of children with cancer are interested in preventing and/or preserving their children’s fertility. But do they know what their options are? Do they even know infertility is a risk? The answer to both, sadly, is often no. However, now that we know the majority of parents would agree to fertility preservation techniques, we may confidently proceed with appropriate clinical trials.

Cancer survival rates have increased dramatically in recent those boys, sperm may be obtainable by masturbation or decades. Until better cancer therapies emerge, infertility will electro-ejaculation. (Despite the misleading name, electro- remain a common side effect of cancer therapy. Infertility ejaculation is not painful.) therapies have likewise flourished in recent decades, but unfortunately the science of infertility has been relatively slow Parents of children with cancer are interested in preventing to infiltrate the oncology world. This dichotomy may in part and/or preserving their children’s fertility. But do they know be attributed to several reasons: Most cancers occur in adults what their options are? Do they even know infertility is a risk? past their peak child-bearing years, sperm banking has been The answer to both, sadly, is often no. available and successful for decades, and in vitro fertilization and other assistive reproductive technologies have been Sperm banking for postpubertal males is routinely offered at successfully used since the late 1970s [1]. some oncology centers and rarely at others. The diagnosis of cancer is usually followed by a flurry of tests, operations, and However, thousands of prepubertal children are diagnosed with the initiation of therapy. In children and adolescents, there cancer every year worldwide, and for them these reproductive is often very little time between diagnosis and the start of technologies are not realistic options. For females, eggs are chemotherapy. Although well known to pediatric oncologists, present at birth in the ovaries and can be harvested, although the risks of infertility are often not explicitly shared with it is technically challenging and rarely done [2]. In prepubertal patients and their parents. There are likely several reasons for boys, sperm are not made until puberty progresses through an this, including lack of certainty and individual variations. But appropriate stage, typically Tanner stage III or IV development, the primary reason probably boils down to this misconception: which for most males occurs around the age of 12 or 13. For Infertility is a price one may have to pay to be cured.

KEYWORDS: Cancer survival, fertility preservation, pediatric cancer CORRESPONDENCE: Thomas W. McLean, Department of Pediatrics, division of Hematology/Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 50. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.09

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.09 ISSN 1944-5792 (print), ISSN 1944-5784 (online) letter to the editor

But does it have to be? Is there time between diagnosis and the initiation of chemotherapy? For most patients the answer is yes. The majority For prepubertal boys, it may be possible in the future to restore of patients undergo surgery for tumor biopsy/resection and/or or improve fertility by re-implanting stored spermatogonial other procedures such as central-line placement, bone marrow stem cells (SSCs) back into the testes after cancer therapy and aspirate/biopsy, or lumbar puncture. With careful planning sexual maturity have been completed. Although animal models and coordination, a testicular biopsy (or ejaculation via show promise in different species [3], including non-human masturbation or electro-ejaculation) can be safely completed primates [4], human trials have not yet been conducted. The in most cases. first step in this therapy would involve testicular biopsy and cryopreservation, ideally before the boy has been exposed to So what are the next steps? Now that we know the majority any chemotherapy agents that could harm his SSCs. Before this of parents would agree to fertility preservation techniques, technology can move forward, it is imperative to know if it we may confidently proceed with appropriate clinical trials. In would be accepted by families. addition, it is imperative that education continues in this arena, not only to parents but also to health-care professionals, and Would parents agree to testicular biopsy? When testicular most importantly pediatric oncologists who are crucial to the biopsy is coupled with sperm banking via masturbation success of such trials. or electro-ejaculation, about two-thirds of parents would agree with fertility preservation interventions if the chance REFERENCES of infertility or successful fertility restoration is at least 80%. Surprisingly, about one-third of parents would agree, even if 1. Steptoe, P. C. and R. G. Edwards (1978). "Birth after the the chance of infertility is low (< 20%) and even if the chance of reimplantation of a human embryo." Lancet 2(8085): 366. successful restoration of fertility is low (< 20%) [5]. Therefore, PubMed all parents should be counseled about the risks of infertility and available fertility preservation options. 2. Ayensu-Coker, L., D. Bauman, et al. (2012). "Fertility preservation in pediatric, adolescent and young adult A parent’s primary objection in this study is that fertility female cancer patients." Pediatr Endocrinol Rev 10(1): 174- preservation interventions may harm their son. This is a 187. PubMed rational concern given the sensitivity to even minor trauma of the testicles. But in fact testicular biopsy is easy and safe, 3. Brinster, R. L. (2007). "Male germline stem cells: from mice with relatively few short- or long-term side effects [6]. A lesser to men." Science 316(5823): 404-405. PubMed | CrossRef parental concern is that the boy should decide such matters for himself. Importantly, the majority of parents surveyed indicated 4. Hermann, B. P., M. Sukhwani, et al. (2012). "Spermatogonial a willingness to donate up to one-third of the testicular tissue for stem cell transplantation into rhesus testes regenerates research. Such research is crucial to facilitate clinical application spermatogenesis producing functional sperm." Cell Stem (i.e., SSC autotransplantation in humans) as soon as possible. Cell 11(5): 715-726. PubMed | CrossRef

This report is limited by its retrospective nature and limitation 5. Sadri-Ardekani, H., M. M. Akhondi, et al. (2013). "Parental to a single country (Iran); however, the acceptance rate for attitudes toward fertility preservation in boys with cancer: different fertility preservation options in this study was in the context of different risk levels of infertility and success rates same range as earlier studies in the Netherlands and the USA of fertility restoration." Fertility and Sterility 99: 796-802. [7,8]. The message is clear: Most parents of pediatric oncology patients are under-informed about fertility implications of 6. Wyns, C., M. Curaba, et al. (2011). "Management of fertility cancer therapy, and most would want their son to undergo preservation in prepubertal patients: 5 years' experience fertility preservation. Predictably, increased infertility risk and at the Catholic University of Louvain." Hum Reprod 26(4): increased theoretical success rates both independently increase 737-747. PubMed | CrossRef parent interest. 7. van den Berg, H., S. Repping, et al. (2007). "Parental desire and acceptability of spermatogonial stem cell Could testicular biopsy tissue contain cancer cells? This is a cryopreservation in boys with cancer." Hum Reprod 22(2): particular concern for patients with leukemia, in whom occult 594-597. PubMed | CrossRef testicular involvement is relatively common (approximately 20%). Among others, a recent report shows the effectiveness of flow cytometry for separating out malignant cells from SSCs, suggesting this problem can be avoided [9].

8. Ginsberg, J. P., C. A. Carlson, et al. (2010). "An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety." Hum Reprod 25(1): 37-41. PubMed | CrossRef

9. Dovey, S. L., H. Valli, et al. (2013). "Eliminating malignant contamination from therapeutic human spermatogonial stem cells." J Clin Invest 123(4): 1833-1843. PubMed | CrossRef

Mohamad Sajid Bazaz, Tanveer Iqbal Dar, Nuzhat Tabasum, Mohammad Saleem Wani, Abdul Rouf Khawaja Submitted March 21, 2013 - Accepted for Publication July 22, 2013 Abstract

Leiomyoma of the ureter is a very rare benign tumor of mesenchymal origin, which may be very difficult to differentiate from malignant tumors before surgery. With the exception of the numerous fibrous polyps, only the occasional example of leiomyomas, neurofibromas, hemangioma, and fibrolipoma have been reported. To the best of our knowledge only 12 cases have been reported worldwide since 1955, with only 1 case of bilateral ureteric leiomyoma. The aim of this report is to highlight the rarity of this tumor and its impact on renal function.

introduction tomography revealed a soft tissue mass lesion in the right upper ureter with a hydronephrotic right kidney with thinned Leiomyoma of the urogenital organs is a very rare tumor, out parenchyma. A diuretic renogram revealed a glomerular and the ureter is an even rarer organ of origin. Total filtration rate (GFR) of 56 mL and 8 mL on left and right sides, nephroureterectomy is often performed because of the respectively, with an obstructive pattern on the right side. In diagnostic dilemma. It usually causes hydronephrosis, making view of a poorly functioning kidney, the patient was taken it difficult to diagnose. However, the possibility of malignancy up for right radical nephroureterectomy. Operative findings can be ruled out by preoperative ureteroscopic biopsy [1]. were a grossly hydronephrotic right kidney with thinned out parenchyma, and a ureter dilated up to the ureterovesical We report a case of primary giant leiomyoma of the ureter in junction containing a hard, cord-like mass, extending from L2 which radical nephroureterectomy was performed because of a up to the ureterovesical junction (UVJ}. The mass tapered at non-functioning ipsilateral kidney. both ends with a whitish smooth surface and a firm consistency (Figure 1). The histopathology showed microscopic features Case report consistent with leiomyoma of the ureter with bundles of smooth muscle fibers (Figure 2). The kidney section showed A 50-year-old female patient presented with 3 episodes of features consistent with hydronephrosis. painless gross hematuria over the last 1 month. There was no other significant history. Baseline investigations included Discussion hemoglobin, 11.5 g%; platelet count, 2 lacs/mm3; prothrombin time, 13; and INR, 1.10. Her urine examination was normal The first case of leiomyoma of the ureter was reported by except for red blood cells full field. Ultrasonography revealed Leighton et al. in 1955 [2]. Since then only 12 cases have been hydronephrotic right kidney with upper hydroureter in the reported [1], making the present case the thirteenth. All cases presence of a normal left kidney. Intravenous urography have been reported in adults (aged 30 to 40 years), apart from revealed a non-visualized right kidney with a normal, 1 case in an infant. The lesions were located in the right ureter functioning left kidney. Contrast-enhanced computed in about 60% of cases with a male-to-female ratio of around 1:1. Upper and lower parts were more commonly involved than

KEYWORDS: Ureteral tumors, leiomyoma, radical nephroureterectomy CORRESPONDENCE: Dr. Tanveer Iqbal, Clinical Assistant, Department of Urology and Renal Transplant Surgery, Sir Ganga Ram Hospital, New Delhi, India, 110060 ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 52. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.11

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.11 ISSN 1944-5792 (print), ISSN 1944-5784 (online) case report the mid-ureter [1]. Figure 2. Bundles of elongated smooth muscle cells with an oblong nucleus and esinophillic cytoplasm. The mechanism of development remains unclear, although inflammation, chronic stimulation, occlusion, and trauma are suspected. In 2 cases, the patient had a history of ureterolithiasis [1]. Ikota et al. reported a diffused leiomyoma of the ureter as a complication of multiple endocrinoma (MEN) type 1 along with leiomyomas in other organs, including the esophagus, stomach, lungs, uterus, and skin [3]. It has been suggested that the MEN type 1-associated gene may have a causal relationship to multiple leiomyomas [3].

Yashi et al, [4] reviewed the literature and discussed clinical features of 8 cases. The classic triad is uncommon and consists of hematuria (75%), pain (60%), and a hydronephrotic mass (45%). There is an uncommon observation of obstruction to the passage of the ureteric catheter during retrograde pyelography in the area of the filling defect, which may cause bleeding through or around the catheter (Chevassu-Mock sign). If the catheter is successfully manipulated past the obstruction, clear or pink urine is obtained (Marion's sign) [5].

The diagnosis is made by diagnostic imaging such as excretory urography, retrograde urography, or computed tomography

Figure 1. A nephroureterectomy specimen showing the tumor arising from the upper ureter and extending up to the ureterovesical junction. The ipsilateral kidney is hydronephrotic. The bladder cuff is also visible.

(CT) and urinary cytology, as for other ureteral tumors, but there are no characteristic findings [1]. Surgical treatment ranges from partial ureterectomy to nephroureterectomy. It has become possible to diagnose benign tumors by preoperative examination as a result of advancements in ureteroscopic technology, and it is important to pay careful consideration to the preservation of renal function [1]. If preoperative studies and intraoperative findings suggest a benign lesion, ureterotomy and biopsy of the lesion for a frozen section may be recommended, with either excision of the tumor or segmental ureteral resection. Such a conservative approach is probably justified in a child if the ipsilateral kidney function is normal. In adults with a poorly functioning kidney, as was the present case, nephroureterectomy is the logical option [5].

Leiomyoma of the ureter should be considered in the diferrential diagnosis of a ureteric tumour, especially in a young adult

Referrences

1. Katsuya, N., Y. Yoshiaki, et al. (2006). "A case of primary leiomyoma of the ureter." Int J Urol 14: 248–250.

2. Leighton, K. M. (1955). "Leiomyoma of the ureter." Br J Urol 27(3): 256-257. PubMed

3. Ikota, H., A. Tanimoto, et al. (2004). "Ureteral leiomyoma causing hydronephrosis in Type 1 multiple endocrine neoplasia." Pathol Int 54(6): 457-459. PubMed | CrossRef

4. Yashi, M., S. Hashimoto, et al. (2000). "Leiomyoma of the ureter." Urol Int 64(1): 40-42. PubMed

5. Shah, S. A., P. Ranka, et al. (2004). "Leiomyoma of ureter - a rare cause of intractable hematuria and clot retention." Indian J Urol 20: 181-182.

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.11 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Isolated Ano-vaginal Fistulae without Associated Vesicovaginal Fistulae Following Prolonged Labor: A Rare Entity

Vishwajeet Singh, Dheeraj Kumar Gupta, Rahul Janak Sinha Submitted May 15, 2013 - Accepted for Publication June 30, 2013

Abstract

Isolated ano-vaginal fistulae without associated vesicovaginal fistulae following prolonged labor have not been reported. They present with fecal discharge per vaginum. A two-layered fistulae closure with interposition flap is the treatment of choice. Herein, we report such a rare entity that deserves mention.

Introduction Figure 1a. A probe in the ano-vaginal fistula.

Vesicovaginal fistula is the most common acquired genitourinary fistula following obstructed labor, but isolated ano-vaginal fistula following obstructed or prolonged labor has not been reported. Such fistula is very bothersome to the patient because of the fecal discharge per vagina. Herein, we report such a case of isolated ano-vaginal fistulae following prolonged labor. The fistula was closed in 2 layers with an interposition flap.

Case report

A 21-year-old primipara presented with a history of passing stools per vagina for 3 months. The patient started passing stools per vagina 1 week following labor. There were no voiding symptoms. The patient had a history of prolonged labor (36 hours) in which she delivered a live baby in a peripheral government hospital. There was no history of episiotomy or a forceps delivery. The fetus had cephalic presentation, but the baby expired 3 days following birth, and the cause of death was unknown. On speculum examination of the vagina, the patient was found to have an isolated, 1.5 cm x 1 cm wide ano-vaginal fistula, 1.5 cm from the vaginal introitus communicating with the anal canal (Figure 1a). The anal sphincter was intact. Cystoscopy ruled out concomitant vesicovaginal fistulae (VVF). The patient was initially managed by sigmoid colostomy. A distal loopogram 3 months following a colostomy showed the typical finding of ano-vaginal fistulae (Figure 1b). The patient

KEYWORDS: Ano-vaginal fistulae, vesicovaginal fistulae, obstetric delivery, interposition flap CORRESPONDENCE: Vishwajeet Singh, M.S.,M.Ch (Urology), Chhatrapati Sahuji Maharaj Medical University (Formerly KGMC), Lucknow, Uttar Pradesh, India ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 48. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.07

Figure 1b. Distal loopogram showing communication Figure 2a. After complete 2-layer closure of the ano- between the vagina and anal canal. vaginal fistula with interposition of the Martius flap.

to ano-vaginal fistulae. Inadequate repair, breakdown of the repair, or infection of episiotomy can all result in fistulae development [2]. was managed by closure of the fistula through the vaginal approach. The closure was done in 2 layers with interposition of In our case, the cause of ano-vaginal fistulae could have a Martius flap (Figure 2a). A repeat distal loopogram confirmed been because of compression of the fetal head against closure of the fistula (Figure 2b). Colostomy closure was done the impacted feces or could be due to the rupture of a pre- after 6 weeks of fistula closure. The vaginal discharge of feces existing, unrecognised anal abscess into the vagina that was stopped following fistula closure, and the patient is doing well superimposed upon prolonged, neglected labor. However the in follow-up. detailed history of the patient ruled out any perianal abscess.

Discussion The obsteteric vesicovaginal fistulae in association or with rectovaginal fistulae have been reported [4,5]. Prolonged labor Ano-vaginal fistulae are abnormal epithelial-lined connections causing isolated ano-vaginal fistulae without concomitant VVF between the anal canal and vagina. The causes of ano-vaginal has not been reported in the literature. Based on the basic fistulae could be obstetric trauma, inflammatory bowel disease, surgical principle of fistulae closure, the fistula was dissected anal surgeries, radiation, and trauma [1]. Prolonged labor with and closed in 2 layers with interposition of the Martius flap necrosis of the ano-vaginal septum or obstetric injury with a similar to VVF repair [3]. Temporary colostomy may or may not third- or fourth-degree perineal tear or episiotomy can lead be required in rectovaginal fistulae closure. The rectovaginal fistulae may be repaired concomitantly with VVF repair [5]. In

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.07 ISSN 1944-5792 (print), ISSN 1944-5784 (online) Case report our case the approach of temporary colostomy and delayed Figure 2b. Repeat distal loopogram 6 weeks after fistula closure of the fistula was followed. closure showed healing of the ano-vaginal fistula.

Conclusion

Isolated ano-vaginal fistulae following prolonged labor is extremely rare and should be managed by fistulae closure in 2 layers and stages.

REFERENCES

1. Songne, K., M. Scotte, et al. (2007). "Treatment of anovaginal or rectovaginal fistulas with modified Martius graft." Colorectal Dis 9(7): 653-656. PubMed | CrossRef

2. Debeche-Adams, T. H. and J. L. Bohl (2010). "Rectovaginal fistulas." Clin Colon Rectal Surg 23(2): 99-103. PubMed | CrossRef

3. Rangnekar, N. P., N. Imdad Ali, et al. (2000). "Role of the martius procedure in the management of urinary-vaginal fistulas." J Am Coll Surg 191(3): 259-263. PubMed

4. Muleta, M., S. Rasmussen, et al. (2010). "Obstetric fistula in 14,928 Ethiopian women." Acta Obstet Gynecol Scand 89(7): 945-951. PubMed | CrossRef

5. Kelly, J. and B. E. Kwast. (1993). "Obstetric vesicovaginal fistulas: Evaluation of failed repairs." Int Urogynecol J 4: 271-273.

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.07 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Squamous Cell Carcinoma Arising in Keratinizing Desquamative Squamous Metaplasia (KDSM) of the Renal Pelvis

Mohammed S. Al-Marhoon, P. A. M. Saparamadu, Krishna P. Venkiteswaran, Omar Shareef, Joseph Mathewkunju Submitted June 7, 2013 - Accepted for Publication July 17, 2013

Abstract

Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract is a rare condition. We present a case of a 45-year-old male smoker of more than 20 years presenting with a 1-month history of recurrent, intermittent left flank pain of moderate intensity associated with dysuria and nausea. In this case the differential diagnosis included renal cell carcinoma, tuberculosis of the kidney, and KDSM. However, the pathological findings showed squamous cell carcinoma arising in KDSM. Hence we report this rare association of a squamous cell carcinoma of the renal pelvis arising in KDSM.

Introduction A physical examination revealed a thin built man with normal vital signs. There was abdominal tenderness in the left flank Keratinizing desquamative squamous metaplasia (KDSM) of the area with no palpable mass. Investigations revealed normal upper urinary tract is a rare condition. It is often referred to by CBC, coagulation, renal functions, electrolytes, bone profile several different names, including cholesteatoma, leukoplakia, LFT, and chest X-ray. HIV 1 and 2 were negative. Hepatitis and hyperkeratosis [1]. The etiology of KDSM includes a reactive screen revealed that he had previous exposure to HBV. epithelial response to chronic irritation (urinary tract infection, Urinalysis, microscopy, and culture showed 500 leucocytes and urolithiasis, tuberculosis, or hydronephrosis) [1]; secondary 300 red blood cells per microliter but no growth. Mantoux test to vitamin A deficiency [2]; representation of a spontaneous for tuberculosis was negative. On computed tomography (CT) epithelial transformation; or representation of a congenital scan of the abdomen and pelvis, there was a complete lack of anomaly whereby abnormal epithelial cells from the ectoderm enhancement in the enlarged left kidney. There were multiple embryologically contaminate the primitive Wolffian duct [3]. cystic areas with peripheral calcifications. The left renal pelvis We are presenting here a rare case of a squamous cell carcinoma was significantly dilated with debris/hematomas seen, and of the kidney arising in KDSM. the wal0-l was thickened and calcified. There were multiple left renal hilum and perinephric lymph hypodense nodes, the Case History largest measuring 1.5 cm. The left renal artery was diffusely attenuated. The right kidney appeared normal. The urinary A 45-year-old male smoker for more than 20 years presented bladder was unremarkable. There was no significant sized with a 1-month history of recurrent, intermittent left flank pain retroperitoneal or mesenteric adenopathy (Figure 1). of moderate intensity associated with dysuria and nausea. He gave a history of losing 5 kg of his body weight during this The patient underwent radical left nephrectomy on the period. However, there was no history of hematuria, fever, suspension of renal cell carcinoma. Intraoperative findings were vomiting, or a history of tuberculosis, diabetes, or hypertension. suggestive of tuberculosis of the kidney due to the finding of There were no features suggestive of paraneoplastic syndromes. an enlarged left kidney with hard cystic changes and many lymph nodes that discharged thick white material. Perinephric

KEYWORDS: Squamous cell carcinoma, metaplasia, kidney CORRESPONDENCE: Mohammed S. Al-Marhoon, PhD, MD, MRCSEd, BSc, Sultan Qaboos University, Al-Khould, Muscat, Oman ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 49. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.08

Figure 1. CT of the abdomen showing an enlarged left Figure 2. Left kidney with cut surface with brown necrotic kidney with calcification and cystic changes (arrow). material mixed with white thick keratin flakes. Note the irregularly enlarged pelvicalecyal system (white arrow) filled with brownish material (red arrow) mimicing tumor necrosis rather than cheesy caseating material of tuberculosis.

Figure 3. H&E; urothelium with adjacent thick hypekeratotic metaplastic squamous epithelium (arrow).

Figure 4. An area of squamous cell carcinoma (some highlighted with arrows).

fat and Gerota’s fascia adhered to the kidney with an intense inflammatory reaction. The pathology revealed a cystic mass with compressed renal medullary tissue over the outer surface of the wall. The cyst lining is of squamous epithelium showing

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.08 ISSN 1944-5792 (print), ISSN 1944-5784 (online) Case report hyperkeratosis and parakeratosis, which was focally ulcerated. At be undertaken regularly. the base of the epithelium there were disorganized, dysplastic, irregular infiltrative down growths of epithelium, indicative of Most tumors of the renal pelvis and ureter are of urothelial origin squamous cell carcinoma. At some foci, the tumor infiltrated the and are, most commonly, transitional cell tumors. Squamous renal capsule. Four lymph nodes examined revealed extensive cell carcinomas and adenocarcinomas may be associated with metastasis. As the metaplasia and the areas of squamous cells chronic infection or stones, but this does not occur frequently. were well differentiated and the morphological diagnosis In those patients at risk for upper tract SCC, a high index of was unequivocal, immune-histochemical investigations were suspicion should be maintained to improve detection of disease not performed. Well-differentiated squamous cell carcinoma at an earlier stage. In our case, which included left radical arising in a desquamative keratinizing squamous metaplasia nephrectomy performed for the suspicion of RCC, the incidental (cholesterotomatous leukoplakia) of the renal pelvis was finding of SCC on histological examination of the nephrectomy diagnosed (Figure 2, Figure 3, Figure 4). On postoperative specimen was found. The standard surgical management of follow-up the patient was well and had gained weight. He upper tract SCC is radical nephroureterectomy. However, in our was referred to oncology for further follow-up. The patient case only radical left nephrectomy was done due to the initial received chemotherapy. However, due to local and metastatic suspicion of RCC. Subsequent completion of ureterectomy was recurrence of the disease, the patient died after 1 year from the not carried out due to the advanced disease of the patient and date of the diagnosis of his disease. the need for chemotherapy.

Discussion Conclusion

Keratinizing desquamative squamous metaplasia (KDSM) has In this case we report this rare association of squamous cell been described coincidentally with squamous cell carcinoma carcinoma of the renal pelvis arising in KDSM. However, (SCC) of the upper urinary tract in 8 to 12% of cases; however, squamous cell carcinoma is a potential risk of keratinizing it has never been demonstrated that SCC arises from KDSM desquamative squamous metaplasia, and conservative [4]. Reece and Koontz, [3] reported 2 cases of concurrent renal management of KDSM needs further support by future studies. pelvis KDSM and neoplasm (1 transitional-cell carcinoma and 1 squamous-cell carcinoma). However, they were unable to REFERENCES provide histological evidence that the KDSM was involved in the tumor. Sheaff et al [5] described a case of squamous cell 1. Hertle, L. and P. Androulakakis (1982). "Keratinizing carcinoma in association with extensive keratinising squamous desquamative squamous metaplasia of the upper urinary metaplasia of the pelvic urothelium. The general appearance tract: leukoplakia--cholesteatoma." J Urol 127(4): 631-635. of KDSM as a space-occupying mass within the kidney prompts PubMed consideration of malignancy. It has been reported that keratinizing squamous metaplasia of the kidney may mimic 2. Liang, F. X., M. C. Bosland, et al. (2005). "Cellular basis transitional cell carcinoma [6]. Keratinizing desquamative of urothelial squamous metaplasia: roles of lineage squamous metaplasia of the renal pelvis without presence of heterogeneity and cell replacement." J Cell Biol 171(5): malignancy has been described bilaterally [7]. 835-844. PubMed | CrossRef

In our case the differential diagnosis included renal cell 3. Reece, R. W. and W. W. Koontz, Jr. (1975). "Leukoplakia of carcinoma, tuberculosis of the kidney, and KDSM. However, to the urinary tract: a review." J Urol 114(2): 165-171. PubMed our surprise the pathological findings showed squamous cell carcinoma arising in KDSM. In this case we prove for the first 4. Denes, F. T. (1984). "Keratinizing squamous metaplasia time in the literature a squamous cell carcinoma of the kidney of the upper urinary tract." Int Urol Nephrol 16(1): 23-28. arising in KDSM. Historically, KDSM of the upper urinary tract PubMed is treated with extirpative surgery. However, Borofsky et al. [8] reported 2 cases of renal KDSM managed conservatively with a 5. Sheaff, M., P. Fociani, et al. (1996). "Verrucous carcinoma nephron-sparing manner with biopsy, diagnostic ureteroscopy, of the renal pelvis: case presentation and review of the and imaging surveillance. They concluded that conservative literature." Virchows Arch 428(6): 375-379. PubMed management of renal KDSM is preferable as it is almost certainly a benign condition. In addition, Ganeshappa et al. [9] reported 6. Boswell, P. D., B. Fugitt, et al. (1998). "Keratinizing conservative management for KDSM. Our case shows that SCC desquamative squamous metaplasia of the kidney is a potential complication of KDSM and we recommend that mimicking transitional cell carcinoma." Urology 52(3): 512- the conservative management of KDSM should be guarded 513. PubMed and, if employed, a vigorous surveillance with renal biopsy to

7. Angulo, J. C., A. Santana, et al. (1997). "Bilateral keratinizing desquamative squamous metaplasia of the upper urinary tract." J Urol 158(5): 1908-1909. PubMed

8. Borofsky, M., R. B. Shah, et al. (2009). "Nephron-sparing diagnosis and management of renal keratinizing desquamative squamous metaplasia." J Endourol 23(1): 51- 55. PubMed | CrossRef

9. Ganeshappa, A., A. Krambeck, et al. (2009). "Endoscopic management of keratinizing desquamative squamous metaplasia of the upper tract: a case report and review of the literature." J Endourol 23(8): 1277-1279. PubMed | CrossRef

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.08 ISSN 1944-5792 (print), ISSN 1944-5784 (online) UIJ UroToday International Journal® Successful En-Bloc Kidney Transplantation from a 7-Month-Old Donor Weighing 14.3 Pounds Into an Adult Recipient: A Case Report

Taqi F. Toufeeq Khan, Suhaib Kamal, Basem Koshaji, Faheem Akhtar Submitted May 2, 2013 - Accepted for Publication June 16, 2013

Abstract

We report a case of successful transplantation of en-bloc kidneys (EBK) from a 7-month-old male pediatric donor weighing 14.3 pounds into a 94.8-pound, 18-year-old female recipient. The cause of brain death in the infant was pseudomonas meningitis, and the donor and recipient received appropriate intravenous antibiotics. Both ureters were implanted separately and stented. The postoperative course was uneventful except for 2 episodes of acute cellular rejection. She remains well at more than 36 months post-transplantation, with a serum creatinine of 48 µmmol/L. We recommend en-bloc kidney transplantation into suitable adults if the pediatric donor weighs less than 33 pounds.

Introduction panel-reactive, negative-antibodied, 94.8-pound, 18-year- old female transplant candidate with end-stage renal disease The use of small pediatric donor kidneys has been limited secondary to hypertension. The recipient had been on regular due to concerns over technical complications and long-term hemodialysis for the last 2 years. This 7-month-old infant with outcomes [1]. To overcome the shortage of deceased donor Down’s syndrome, weighing 14.3 pounds, became a deceased kidneys, the transplantation of small pediatric kidneys into donor secondary to pseudomonas meningitis and was treated suitable adult recipients has become an acceptable option [2,3]. with piperacillin/tazobactam. Because of the risk of infection, Using both kidneys provides adequate nephron mass for adult the recipient was also given a 7-day course of piperacillin/ recipients, with outcomes similar to standard criteria adult tazobactam. The cytotoxic and flow cytometery cross-matches kidneys [3-5]. With refinements in surgical technique and the were both negative, with a 4-antigen mismatch, the only use of ureteral stents, the vascular and ureteral complications matches being DR4 and A26. This recipient had recently associated with pediatric kidneys have been reduced [6]. To completed a 7-month course of treatment for pulmonary make better use of this limited resource, there are those who tuberculosis and received rifampicin and isoniazid for 2 months advocate adult recipients be given single pediatric kidneys [7]. after transplantation. Even though pediatric kidneys have been reported to have a higher incidence of acute rejection, they have excellent long- Both donor kidneys were recovered en bloc with long term results [8,9]. We report the successful transplantation of infrarenal segments of aorta and vena cava (Figure 1a). en-bloc kidneys (EBK) from a 7-month-old, 14.3-pound donor Superiorly, the aorta was divided at the celiac axis and the into an adult recipient. vena cava just below the liver to enable a secure suture closure of both these proximal stumps. At the back table, the Case report superior mesenteric artery stump was ligated, followed by closure of both aortic and vena caval stumps with a running A set of EBK from a 7-month-old donor was allocated to a 7/0 polypropylene suture, which was negative for leaks. The implantation was extra peritoneal in the right iliac fossa, both

KEYWORDS: 14.3-pound pediatric donor, bacterial meningitis, en-bloc kidneys, kidney transplantation, adult recipient CORRESPONDENCE: Taqi F. Toufeeq Khan, Section of Kidney Transplantation, Department of Surgery, Riyadh Military Hospital, 11159 Riyadh, Kingdom of Saudi Arabia ([email protected]) CITATION: UroToday Int J. 2013 August;6(4):art 45. http://dx.doi.org/10.3834/uij.1944-5784.2013.08.04

©2013 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 6 / Iss 4 / August / http://dx.doi.org/10.3834/uij.1944-5784.2013.08.04 ISSN 1944-5792 (print), ISSN 1944-5784 (online) case report vascular anastomoses were carried out end to side between Figure 1a. En-bloc kidneys after back table preparation. the distal aorta and vena cava, and the external iliac vessels Long segments of aorta (red arrow) and inferior vena used running 6/0 polypropylene sutures. Both kidneys perfused cava (blue arrow) and their sutured proximal stumps very well (Figure 1b). The 2 ureters were implanted separately (black arrows) are visible. The ligated stump of the using the extravesical technique and stented (Figure 2a and superior mesenteric artery is also shown (yellow arrow). Figure 2b). The recipient received anti thymocyte globulin (ATG) and methylpredinsolone induction during surgery. Graft function was immediate, with a cold ischemia time of 6 hours 20 minutes and a rewarming time of 37 minutes. Next- day Doppler ultrasound (DUS) and subsequent 99m-Tc nuclear scans confirmed good perfusion and excretion in both kidneys (Figure 3a, Figure 3b, and Figure 4). Since she had recently completed a 7-month course of antituberculous therapy, the ID team recommended that she receive rifampicin and isoniazid for another 8 weeks. The maintenance immunosuppression included tacrolimus, mycophenalate mofetil, and prednisolone, and it was difficult to maintain tacrolimus levels of 8 to 10µg/L because of rifampicin. She suffered biopsy-proven acute cellular rejection (ACR) in the second and fourth weeks that responded to steroids. Rifampicin was discontinued 8 weeks after transplantation and helped achieve adequate tacrolimus levels. She has remained well since, the kidneys have increased in size to over 8 cm, and serum creatinine 36 months after transplantation was 48 µmmol/L. Figure 1b. En-bloc kidneys after reperfusion. Distal ends of aorta and inferior vena cava are anastomosed to the Discussion external iliac vessels; long segments of aorta (red arrow), cava (blue arrow), and proximal stumps are visible (black The ever-increasing demand for kidneys has brought about arrows). Both renal arteries and veins (left artery and the acceptance of pediatric donor kidneys for use in adults vein are indicated with white arrows) and ligated SMA [1,3-5]. Despite earlier concerns with surgical complications stump are also seen (yellow arrow). [6] and poor outcomes in this age group, recent data suggests that adult candidates receiving en-bloc pediatric kidneys have better long-term results than standard criteria donors [3,4] and may even be equal to live donor kidneys [10]. The registry data from 2003 showed a greater risk of graft loss when single kidneys were used from donors less than 46.3 pounds, and this supported the use of en bloc kidneys rather than single kidneys in donors under the age of 5 or weighing less than 44 pounds. Our donor was 7 months old and weighed only 14.3 pounds, with the kidneys measuring 5 cm. We decided to transplant them en bloc into a suitable adult female recipient who weighed 94.8 pounds. If this donor was a little older and weighed over 33 pounds, we might have considered splitting the kidneys for 2 adults, but with a donor weight of 14.3 pounds, en-bloc implantation was the logical and, in hindsight, correct choice. The recommended practice is to use EBK from donors aged 5 or at a weight of 44.3 pounds. However, Borboruglu reported good results with single kidneys from donors less than 2 years but who weighed more than 30.9 pounds and had a kidney length of 6 cm. Efforts should be made to recover kidneys from antibody. Knowing that EBK has outcomes similar to living small pediatric donors as “en bloc,” which have been shown to donors, we wanted a young recipient in an attempt to get result in a higher probability of transplantation [4,12]. We were the best possible longevity match. A female with a low body strict in the choice of our recipient and decided on a young mass index was chosen so as not to expose the infant kidneys female with a low body mass index and a zero-panel reactive to an excessive creatinine load, and to avoid hyperfiltration by

Figure 2a. Plain abdominal film showing both double-J Figure 2b. A double-J stent is seen within a transparent stents in place; skin clips and the Jackson Pratt drain are right ureter (white arrow). The left kidney is placed on also visible. the bladder (blue star) and the right kidney (black arrow) on the slope of the iliac bone under the oblique muscles. The aorta, a long, right renal artery (yellow arrow) and left renal artery (thin black arrow) are also seen.

Figure 3a. En-bloc kidneys on ultrasound scan.

Figure 3b. Well-perfused en-bloc kidneys on DUS. Kidney labeled 1 is laying on the bladder (white arrow).

matching the nephron requirement to the available nephron mass. Technical complications remain a concern, but meticulous attention to detail is important to prevent vascular and ureteric complications. This is especially the case in single pediatric kidneys where the individual vessel size is small and prone to thrombosis, and all ureteroneocystostomies should be stented. Additionally, we paid a lot of attention to the final placement of the EBK to prevent them from twisting or falling over, which could result in thrombosis and graft loss.

The increasing demand for donor kidneys has also resulted in an expansion of the donor pool by broadening the selection

Figure 4. The 99m-Tc nuclear scan showing good xREFERENCES perfusion and excretion in both kidneys. One kidney is seen laying on the bladder. 1. Arrazola, L., H. Sozen, et al. (2000). "Kidney transplant using pediatric donors--effect on long-term graft and patient survival." Transplant Proc 32(7): 1839. PubMed | CrossRef

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