Urotoday International Journal Volume 5 - February 2012 Table of Contents: February, 2012

® UIJ UroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Table of Contents: February, 2012

Review • Lower Urinary Tract Management in Patients with Neurological Disease Marcus J Drake, Francisco MJ Cruz

Lower Urinary Tract Dysfunction • Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression Paul F Siami, Knox Beasley

Overactive Bladder • Prevalence and Risk Factors Associated with Overactive Bladder Christopher Chee Kong Ho, Teo Chee Yang, Phang Lay Fang, Nur Aziyana Noor Azizi, Farah Lyna Darwin, Nur Afifah Mohd Ghazi, Guan Hee Tan, Eng Hong Goh, Praveen Singam, Badrulhisham Bahadzor, Zulkifli Md Zainuddin

Penile Cancer • Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil Rógerson Tenório de Andrade, Marina de Andrade Lima Arcoverde, Fábio de Oliveira Vilar, Misael Wanderley Santos Jr, Nicodemos Teles Pontes Filho, Salvador Vilar Correia Lima

Ureteric Calculi • Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access Hammouda Sherif, Osama Abdelwahab, Abdelaziz Omar, Ibrahim Eraky

Case Reports • A Rare Cause of Acute Urinary Retention in a Young Female: Leiomyoma Bladder Bikash Bawri, Rajeev T Puthenveetil, Saumar J Baruah, Sasanka K Barua, Puskal K Bagchi

• Inflammatory Pseudotumor of the Urachus Raj Kumar Sharma, Vir Kumar Jain, S Mukherjee, SN Mondal, D Karmakar

• Lymphoepithelioma-like Carcinoma of the Bladder: Is the Prognosis Different from Conventional Bladder Carcinoma? Eng Hong Goh, Akhavan Adel, Praveen Singam, Christopher Chee Kong Ho, Guan Hee Tan, Badrulhisham Bahadzor, Zulkifli Md Zainuddin, Isa Mohamed Rose

©2012 Digital Science Press, Inc. / UIJ / Vol 5 / Iss 1 / February http://www.urotodayinternationaljournal.com ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJ UroToday International Journal • Mondor’s Disease of the Penis: A Forgotten Entity Kapil Singla, Ashish K Sharma, Sistla B Viswaroop, Ganesh Gopalakrishnan, Sangam V Kandasami

• Retroperitoneal Textiloma Mimicking an Adrenal Tumor Rahul Devraj, Vedamurthy Pogula Reddy, Surya Prakash Vaddi, Ajit Vikram, Sreedhar D

• Teratoid Wilms Tumor in a Child: A Case Report Jameel Hisham Bardesi, Ahmed Jalal Al-Sayyad

• Treatment of Post, High-Intensity-Focused Ultrasound Urethral Stricture with Novel Long-term Stent Omri Nativ, Sarel Halachmi, Boaz Moskovitz, Ofer Nativ

• Ureteral Diverticulum in Adults: Diagnostic Problems and Therapeutic Implications Satâa Sallami, Sami Ben Rhouma, Ali Horchani

©2012 Digital Science Press, Inc. / UIJ / Vol 5 / Iss 1 / February http://www.urotodayinternationaljournal.com ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Lower Urinary Tract Management in Patients with Neurological Disease

Marcus J Drake,1 Francisco MJ Cruz2 1University of Bristol, Bristol Urological Institute, Southmead Hospital, Bristol, United Kingdom 2Department of Urology, Hospital São João, Faculty of Medicine of Porto and IBMC, Alameda Hernani Monteiro, Porto, Portugal Submitted April 26, 2011 - Accepted for Publication January 17, 2012

ABSTRACT

Lower urinary tract dysfunction is common in patients with neurological disease. Storage and/or voiding function can be affected, leading to bothersome symptoms. However, preventing upper urinary tract deterioration is a greater clinical priority, requiring identification of patients at risk, early intervention where indicated, and ongoing surveillance. An initial assessment requires a comprehensive evaluation, including wider issues such as aspirations for independent living, cognitive function, manual dexterity, and mobility. Measures to improve urine storage include antimuscarinic drugs, botulinum injections, or surgical procedures. For voiding dysfunction, intermittent catheterization is by far the most effective and most widely applicable approach, with additional benefits for urinary storage. The assessment of urinary tract function and treatment selection requires a multidisciplinary approach in the context of full rehabilitation or support.

INTRODUCTION organizations, such as the International Consultation on Incontinence and the European Association of Urology [1,2]. The initial clinical evaluation of the urinary tract in a patient National consensus statements have also been developed (for with neurological disease is crucial as presentations and example [3,4]). prognoses vary, and the outcome is dependent on an accurate assessment. The key aims are: 1) to detect risk factors for the Fundamentally, neurological patients should be assessed by a future (especially renal failure), 2) to optimize life expectancy, suitably trained health care professional who has specialized and 3) to evaluate symptoms, thereby guiding management to knowledge of lower urinary tract dysfunction, and the optimize quality of life. appropriate follow-up surveillance is needed at intervals. Lower urinary tract (LUT) issues have to be managed in the context of There are useful guidelines published by international the wider health issues of the individual. These include directly

KEYWORDS: Neurourology; Detrusor overactivity; Urodynamics; Antimuscarinics; Botulinum toxin A CORRESPONDENCE: Marcus J Drake, MA, DM, FRCS (Urology), University of Bristol, Bristol Urological Institute, Southmead Hospital, Bristol, BS10 5NB, United Kingdom ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 95. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.13

UroToday International Journal review UIJ Lower Urinary Tract Management in Patients with Neurological Disease relevant aspects, such as bowel and sexual function, and the 3) establish lower urinary tract function (storage, voiding), impact of LUT dysfunction on psychological, domestic, social, 4) detect unexpected problems; e.g., lower motor neuron and employment rehabilitation. Accordingly, multidisciplinary deficits may point towards secondary changes needing early expertise is needed in medical teams managing patients with intervention (e.g., syringomyelia in spinal cord injuries), and neurological disease, where the urological element is one of 5) influence further management options (coordination and several important aspects. cognitive tests are rarely untaken but may be appropriate as they influence the choice of management options). CLINICAL EVALUATION A general urological examination looks for distended bladder/ Medical History hydronephrosis, prostate size, pelvic organ prolapse (POP), continence/fecal impaction, and sacral/dependent sores. A The neurological diseases a urologist sees most commonly focused neurological examination looks at key features, such are spinal cord injury (SCI), multiple sclerosis (MS), and spina as: 1) lower limb reflexes and bulbocavernosus reflexes, sensory bifida (myelomeningocele). The range of possible neurological dermatomes (fine touch and pin prick) of the lower limbs, diseases is substantial, with many unfamiliar to the urologist. In and perianally effects, to see which spinal cord segments are general, they can be considered as follows: affected, 2) anal tone and voluntary pelvic-floor squeeze, and 3) the evaluation of other facets; for example, coordination or 1. Level(s) of nervous system affected: brain, upper motor blood pressure (lying and standing) should be considered. neuron spinal, lower motor neuron spinal, peripheral, and combination of the above INVESTIGATION 2. Sensory and/or motor deficit 3. Complete or incomplete neurological impairment Urinalysis 4. Cognition 5. Possible progression of neurology Asymptomatic bacteriuria may subsequently turn into a urinary tract infection, which may become severe due to a lack of After the neurological disease has been understood, the general awareness of early symptoms in people with impaired sensory history covers: 1) social factors and the patient’s motivation, function. 2) relevant surgery, 3) drug history, 4) bowel function, 5) gynecological/obstetric history and hopes for future fertility, Serum Tests of Renal Function and 6) sexual function. Allowance has to be made for muscle mass, considering disease Additionally, urinary tract history covers: 1) possible alarm signs, is often lower in able-bodied individuals, and it will influence such as pain, urinary tract infection, hematuria, and fever that the normal range for serum creatinine values. warrants further specific diagnosis, 2) LUT symptoms related to storage and voiding phases, including urinary incontinence and Imaging Tests bladder sensation, 3) current bladder management methods, including intermittent catheterization, and 4) urinary infections Specific tests depend on the findings of a clinical evaluation. (remembering the symptoms are unreliable where sensation In most cases, the following are appropriate: 1) ultrasound, to below the neurological lesion is impaired [5]). look for upper urinary tract (UUT) changes, 2) hydronephrosis, post-void residual, calcification, and other lesions, and 3) flow Symptom assessment tools are important to catalogue problems rate testing. and their severity [6]. A bladder diary gives information about frequency, daytime and nighttime voiding frequency, voiding Flow rate patterns include normal, interrupted, prostatic, volume, incontinence, and urgency episodes [7]. This is useful or stricture. The interrupted pattern is commonly seen in for making treatment decisions and assessing response. neurological patients and signifies poorly sustained detrusor contractions, straining, or dyssynergia. Artifacts have to be Examination excluded.

The examination aims to: 1) locate neurological lesions, 2) Other tests are required, according to specific clinical establish if other organ systems are affected; e.g., bowels, requirements:

UroToday International Journal review UIJ Lower Urinary Tract Management in Patients with Neurological Disease present 1. IVU / CTU: many neurological patients are at risk of forming 11. To gauge detrusor contractility urinary tract stones, and 12. To look at problems of coordination of outlet and bladder 2. spine/brain imaging: if there is doubt as to neurological contraction (detrusor-sphincter dyssynergia [DSD]) lesion location or progression; however, this is most 13. Post-void residual appropriately discussed with the relevant neurologist. Detrusor leak point pressure (DLPP) is assessed in patients Urodynamics with reduced filling compliance (for example, patients with myelomeningocele, or where there is a neurological lesion Urodynamics is an invasive test with risks attached, so careful of the sacral spinal cord). The DLPP is the detrusor pressure consideration is needed before proceeding with formal filling associated with leakage. When the compliance curve exceeds cystometry and pressure/flow studies. The EAU guidelines make the outlet resistance, high values cause anxiety for future upper a grade A recommendation that urodynamic investigation is urinary tract function [9]. (Abdominal leak point pressure is a necessary to document the (dys)function of the LUT. different concept, unrelated to the risk of renal impairment, giving an indication of incontinence severity in patients with Key urodynamic questions can be addressed by videourodynamics normal bladder compliance). (VUDS): Electromyography (EMG) can register the activity of the external 1. Are the patient’s kidneys at risk because of LUT dysfunction? urethral sphincter, the periurethral striated musculature, the 2. What is the cause of a patient’s LUT symptoms? anal sphincter, or the striated pelvic-floor muscles. It signifies the patient’s ability to control the pelvic floor and objectively Certain neurological patients may be considered at risk of identifies DSD, though the pressure trace alone can be used to LUT deterioration (especially SCI and spina bifida). They will deduce the presence of DSD in the absence of EMG recording generally need pressure flow studies. Those neurourological patients who, in the opinion of the managing clinician, are at Ambulatory urodynamics uses natural filling by the kidneys. a lower risk of renal dysfunction, and who have LUT symptoms, It can be used where conventional VUDS fails to reproduce a should only have invasive pressure flow studies if conservative patient’s symptoms. For example, wheelchair users with stress treatment has failed, the patient is bothered by the symptoms, incontinence symptoms may not be able to exert themselves and they are fit for management interventions. sufficiently to elicit stress incontinence in the confines ofa standard urodynamic test. Ambulatory testing should allow Invasive urodynamic tests should be in accordance with the them the freedom to undertake the activity that reliably elicits International Continence Society good urodynamic practices symptoms. [8]. Key issues are: use a slow filling rate (at least at the start of filling), and minimize the risk of artifactual reduction in The ice water test is fast-filling cystometry with cooled saline. compliance. The use of video screening is important because The ice water test has reportedly distinguished between an of the range of apparent filling and voiding abnormalities. upper motor neuron lesion (UMNL) and lower motor neuron In most cases, the bladder should be emptied at the start of lesion (LMNL) [10]. It is not widely used outside a research filling, though the investigator may vary this according to the setting. circumstances. Safety for the Patient During UDS 1. Filling cystometry 2. To detect detrusor overactivity Specific issues require caution when undertaking a VUDS test in 3. To ascertain the cause of incontinence neuropathic patients. 4. To check leak point pressures 5. To look for vesicoureteric reflux 1. UTI: Urine should be screened before filling cystometry. 6. To check compliance If bacteriuria is present, the test should be deferred until 7. To find cystometric capacity resolved, or prophylaxis should be administered. 8. To evaluate pelvic-floor support 2. Autonomic dysreflexia [11]: A life-threatening complication 9. Voiding studies of SCI above T6, in which extreme hypertension arises 10. To exclude bladder outlet obstruction or identify its site, if acutely in response to a noxious stimulus below the injury

UroToday International Journal review UIJ Lower Urinary Tract Management in Patients with Neurological Disease level. Severe headache can be followed by intracerebral pathways is a requirement. Patients who may benefit are those hemorrhage and death. If the patient complains of with suprasacral spinal cord lesions who are able to collect headache, the bladder should be emptied. Other stimuli urine in a socially acceptable way. The presence of severe DSD should be excluded (i.e., any additional noxious stimulus must be excluded. below the neurological level), antihypertensives should be administered (e.g., sublingual nifedipine), and monitoring Bladder Expression (Credé and Valsalva Maneuvers) instituted. 3. Latex allergies: Neuropathic patients are at risk of a latex Bladder expression has been recommended to patients with an allergy [12] and may manifest an anaphylactic response underactive detrusor combined with an underactive sphincteric [13]. Latex-free settings for VUDS are important, as mechanism. It is no longer supported by most clinicians due a remarkably small level of exposure can trigger an to the risk of infection, vesicoureteral reflux, hernias, and anaphylactic response. rectogenital prolapses. 4. Erroneous conclusions: If VUDS is not carried out satisfactorily, inappropriate management decisions may Toileting Assistance result. Toileting assistance aims to correct habitual patterns of liquid TREATMENT intake and urination, to improve bladder control under urgency, and to teach patients how to reduce incontinence Treatments are often a compromise between 2 main objectives: episodes. Techniques include timed voiding, prompted voiding, firstly, the protection of the upper urinary tract from deleterious habit retraining, bladder retraining, and a patterned response effects of high intravesical pressures, and secondly, the to urgency. improvement of storage and voiding symptoms. Restoration of nervous system function is not currently possible, but it is a Catheters hope for many patients. Overall, the evidence base for catheter use in neurourology Risk of Renal Failure in Neurological Disease is limited [16]. Excellent intermittent catheterization (IC) outcomes in neurogenic patients with various LUT dysfunctions Upper urinary tract deterioration, which may be clinically put it in the management forefront. “silent” until advanced, is a crucial factor in neurourological management. Four main risk factors have been identified for Intermittent Catheterization upper urinary tract damage in MS [14]: 1) the duration of MS, 2) the presence of an indwelling catheter, 3) high-amplitude Intermittent catheterization (IC) can protect renal function neurogenic detrusor contractions, 4) permanent high detrusor and facilitate the achievement of urinary continence, either pressure, and 5) DSD. alone or in combination with other treatments. The frequency of catheterizing should be tailored according to fluid intake, Accordingly, these factors warrant consideration of more active bladder capacity, and detrusor pressure. Frequent urinary tract surveillance of the upper urinary tract. However, the factors infections (UTIs) can occur, but prophylactic antibiotics are are debatable in context. There is a paucity of irrefutable not recommended, and active treatment should be confined evidence relating to the risk factors of renal deterioration in to symptomatic UTI. One fifth of the patients on long-term modern practice, and for the range of neurological diseases. IC will experience urethral complications; e.g., bleeding and For example, in SCI, an indwelling catheter protects against stricture. Sterile IC is associated with lower bacteriuria/infection subsequent deterioration [15]. risk as opposed to clean IC. Fully sterile approaches, using entirely sterile materials, including gloves and forceps, are most BEHAVIORAL TREATMENT frequently advocated for intensive care units. Auto-lubricated catheters, which require immersion for a few seconds in Triggered Reflex Voiding drinking water to activate the lubricating film, are catheters of 12 to 14 Fr and are suitable for most adult male and female Triggered reflex voiding comprises maneuvers performed patients. by the patient to trigger reflex detrusor contractions, such as suprapubic percussion. The integrity of the sacral reflex Indwelling Urethral and Suprapubic Catheters

UroToday International Journal review UIJ Lower Urinary Tract Management in Patients with Neurological Disease will decrease urethral closing pressure. Short-term urethral catheterization is needed in the initial phase of spinal shock. It is not appropriate in the longer term. BTX-A in Neurogenic Detrusor Overactivity A dilated (“patulous”) urethra can result in women, and urethritis, trauma, and stricture can form in men. If patients Schürch and colleagues [22] reported a bladder injection of cannot perform IC, a suprapubic catheter (SPC) is preferable. BoNT/A for neurogenic detrusor overactivity (NDO) of a spinal Due to bladder cancer risks [17], regular cystoscopy is necessary origin resistant to anticholinergic drugs, in a patient who after 5 to 10 years. emptied the bladder by IC. Each patient received 300 units of onabotulinum A (Botox) diluted in saline (10 UI/ml) and injected PHARMACOLOGICAL TREATMENT in 30 different locations above the trigone. A significant increase in bladder capacity and a significant decrease in Drugs for Detrusor Smooth Muscle Relaxation maximum detrusor voiding pressure were still present 36 weeks later. A multicentric European study with Botox in 200 Antimuscarinic agents neurogenic LUTD patients using IC or an indwelling catheter achieved continence in 73%, most benefitting at 9 months [23]. Antimuscarinic drugs aim to decrease reflex incontinence by A recent and large randomized clinical trial with spinal cord delaying nonvoluntary detrusor contraction in patients who injury and multiple sclerosis patients showed that 200 and 300 void spontaneously or empty the bladder by triggered voiding. units of onabotulinum A were equally effective to improve They also aim to decrease high intravesical pressure in patients or cure urinary incontinence and decrease detrusor pressure, with DSD. In conjunction with IC, 70% of patients with less but adverse events, mainly urinary retention and urinary tract severe neurogenic LUT dysfunction may achieve continence. infections, were more frequent with the 300 unit dose [24]. The evidence base for this patient group is small. Muscarinic receptor antagonists cause a variety of side effects, including Patients should understand that, following BoNT/A, urinary dry mouth and constipation. They are contraindicated in closed retention is likely, and patients should be willing to accept angle glaucoma. Oxybutynin, tolterodine, propiverine, and a transient period of IC. A minimum interval of 3 months trospium are the most extensively studied in the treatment between BoNT/A injections might be considered to reduce of neurogenic LUT dysfunction. They significantly reduce the risk of antibody formation. Mild muscular weaknesses in micturition frequency and the number of urinary incontinence the upper extremities of patients with complete cervical cord episodes, and they increase maximal cystometric capacity. lesions rarely arise. Often, these patients will require doses higher than those recommended by the manufacturers [18,19]. The addition of Drugs That Decrease Bladder Outlet Resistance a second antimuscarinic agent may also be tried in patients for whom urinary incontinence or detrusor pressure is not Alpha-1 adrenergic antagonists adequately controlled with 1 single agent [19]. Evidence to support the use of alpha-1 adrenergic blockers Intravesical instillation is an interesting option. Sometimes in neurogenic LUT dysfunction is sparse. Alpha-blockers may purified oxybutynin preparations are available, usually as also contribute to decreased excessive sweating, secondary to vials containing 5 mg. In most countries, there are no such autonomic dysreflexia [25]. formulations. Thus, 5 mg of oxybutynin tablets are crushed and dissolved in 30 ml of distilled water or saline and instilled 2 or 3 Urethral sphincter injections of BTX-A times per day. They are left until the next voiding, as maximum effect may take 2 to 4 hours. BoNT/A injected in the urethral sphincter aims to decrease bladder outlet resistance and facilitate bladder emptying, as an Acetylcholine release inhibitors alternative to urethral sphincterotomy. It can be undertaken in conjunction with bladder injections [26]. Decreased urethral Botulinum toxin (BoNT/A) impedes the release of closure pressure, bladder pressure during voiding, and post-void neurotransmitters from nerve endings. It is increasingly used residual urine are seen, and episodes of autonomic dysreflexia in neurogenic LUT dysfunction [20,21]. In the bladder, the are reduced [27]. blockade of acetylcholine release reduces detrusor contractility, and it may affect afferent nerve function. In the sphincter, it Central nervous system polysynaptic inhibitors

UroToday International Journal review UIJ Lower Urinary Tract Management in Patients with Neurological Disease sphincter, and it may reduce episodes of autonomic dysreflexia. Baclofen is a GABAB receptor agonist that decreases the release TUS applies to male patients, as a penile condom catheter will of sensory neurotransmitters in the spinal cord. In theory, this be needed subsequently to collect urine. Prosthesis infection may depress the activation of the bladder reflexes. However, and penile erosions are too high to use an implant to aid oral baclofen has demonstrated poor efficacy in the treatment condom use. TUS is expected to be a permanent solution but of neurogenic DO (perhaps due to poor CNS penetration). there is a significant rate of failure [29], and severe bleeding or Improvement of NDO is seen with intrathecal administration stricture formation can occur. of baclofen. Permanent urethral stents Substances That Decrease Sensory Input The application of permanent urethral stents in the area of the Capsaicin extracted from hot chili peppers and resiniferatoxin urethral sphincter may constitute an alternative to TUS [30]. (RTX) extracted from euphorbia resinifera, a cactus-like plant However, stent placement may trigger autonomic dysreflexia, abundant in Northern Africa, are the most well studied and migration, encrustation, infections, or fistula are problems compounds of the vanilloid family. These compounds have been and outcomes that are uncertain. in use clinically, and were found to have benefits. They are not commercially available, but they remain a source of potential Operations That Decrease Detrusor Contractility development for future therapeutic interventions. The name “vanilloid” derives from the presence of a homovanillyl ring. Bladder augmentation with intestine Compounds with similar properties may not possess this ring. Vanilloid substances bind to a receptor belonging to the Bladder augmentation should be undertaken only when less transient receptor family, a vanilloid 1 subtype (TRPV1, or VR1 invasive measures fail to create a low-pressure continent or in the old terminology) that occurs in the membrane of type reservoir of sufficient volume. Bladder augmentation with a C, unmyelinated sensory fibers. This causes a brief excitation detubularized intestinal segment is well established. In short, followed by a prolonged desensitization during which the 20 to 30 cm of ileum is isolated and detubularized, and then neuron is unresponsive to natural stimuli. sutured over a transverse cystostomy [31]. Outcomes can be reasonable but may not be sustained [32], while complications SURGICAL TREATMENT might include urine reabsorption, urolithiasis, obstruction due to mucus accumulation, frequent UTIs, bladder rupture, and Many patients with chronic debilitating LUTS, refractory some risks of cancer development in the region of the intestinal to conservative measures, will eventually require surgical patch. Most patients will require IC. procedures. Such procedures require careful evaluation of the patient. Careful urodynamic evaluation is important to establish Bladder auto augmentation the range of upper urinary tract dysfunctions present, so that appropriate plans can be made according to clinical need. For Bladder auto augmentation (detrusor myectomy) [33] involves example, for a patient who hopes to achieve continence, the extraperitoneally stripping the detrusor layer from the dome urodynamic evaluation of the bladder and the outlet enables and anterior surface of the bladder wall to create a large the clinician to identify potential needs in relation to achieving epithelial diverticulum. The technique is now infrequently used. sufficient stable reservoir capacity and a catheterizable continent outlet. Neuromodulation and denervation procedures

Operations That Decrease Outlet Resistance Neuromodulation of the posterior sacral roots has been investigated in idiopathic DO. Some centers have reported DSD can be difficult to manage, and the currently available results in NDO, but it is not widespread. Sacral neuromodulation options have important limitations [28]. was recently shown to have the potential to prevent NDO in patients with spinal cord injury if initiated at the phase of Sphincterotomy spinal shock [34]. This intriguing observation was carried out in a small number of patients and requires confirmation. Transurethral sphincterotomy (TUS) aims to reduce intravesical pressure mediated by bladder contractions against a contracted Subtrigonal denervation using phenol injections provided

UroToday International Journal review UIJ Lower Urinary Tract Management in Patients with Neurological Disease inconsistent results and major complications, so it is no longer by transferring motor nerves in the L5 ventral root onto the in use. S2/3 ventral root. Micturition was later initiated by stimulating the L5 dermatome. However, the useful results reported [39] Operations That Increase Sphincteric Resistance have yet to be reproduced by other centers, raising significant uncertainty about the procedure. Artificial urinary sphincters have been frequently used in patients with congenital neuropathies. Success rates vary CONCLUSION between 70 to 95%, with a revision rate of 16 to 60%. It is effective in most male patients [35]. In female patients, there Neurourology is a challenging subspecialty requiring can be significant problems [36]. considerable resources. Careful specialized evaluations are needed to identify the risk factors for renal deterioration. Operations That Modulate Detrusor Contractility Symptom management requires a fastidious approach to diagnosis and a realistic insight into the patient’s preserved Sacral anterior root stimulation to modulate detrusor functions in order to identify realistic options to restore bladder contractions storage function and emptying. Patients should have access to the full range of therapeutic options, and the more complex Brindley and Craggs developed sacral anterior root stimulation, cases should be managed in appropriate specialist centers. which is indicated in patients with suprasacral spinal cord lesions exhibiting severe DSD and autonomic dysreflexia. It comprises REFERENCES a posterior S2-S4 complete rhizotomy and the implantation of electrode stimulators on the intact sacral anterior roots. 1. Abrams P, Andersson KE, Birder L, et al. Fourth International Anterior root stimulation activates simultaneous detrusor Consultation on Incontinence Recommendations of contractions when voiding is desired. It also activates urethral the International Scientific Committee: Evaluation and closure, but the latter fatigues quickly. Positive outcomes have treatment of urinary incontinence, pelvic organ prolapse, been reported [37]. It can also be used to facilitate bowel and fecal incontinence. Neurourol Urodyn. 2010;29(1):213- emptying, and some males use it for erections. 240. PubMed ; CrossRef

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29. Pan D, Troy A, Rogerson J, et al. Long-term outcomes of 39. Xiao CG. Reinnervation for neurogenic bladder: historic external sphincterotomy in a spinal injured population. J review and introduction of a somatic-autonomic reflex Urol. 2009;181(2):705-709. PubMed ; CrossRef pathway procedure for patients with spinal cord injury or spina bifida. Eur Urol. 2006;49(1):22-28. PubMed 30. Abdul-Rahman A, Ismail S, Hamid R, Shah J. A 20-year follow-up of the mesh wallstent in the treatment of detrusor external sphincter dyssynergia in patients with spinal cord injury. BJU Int. 2010;106(10):1510-1513. PubMed ; CrossRef

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©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.13 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression

Paul F Siami, Knox Beasley Research Institute of Deaconess Clinic, Evansville, IN, USA Submitted October 24, 2011 - Accepted for Publication December 15, 2011

ABSTRACT

Purpose: The primary aim of this study was to investigate whether initial therapy with dutasteride followed by dutasteride with as-needed tamsulosin can prevent symptom progression in patients at a high risk of clinical progression of benign prostatic hyperplasia (BPH). Patients and Methods: This study was an open-label, single-site pilot study of 63 patients. Patients were men > 50 years of age, with a clinical diagnosis of BPH based on medical history, symptom scores, and medical exams. Each patient was prescribed 0.5 mg once daily of dutasteride for 1 year, at which time 0.4 mg once daily of tamsulosin was added. After 3 months of combination therapy, subjects were counseled to taper or discontinue tamsulosin and to restart only on an as-needed basis. Patients returned to the clinic at 6, 9, and 12 months when they were evaluated and drug compliance was measured. Results: Adding tamsulosin to dutasteride resulted in a 41% improvement in IPSS and a 62% improvement in Qmax after 3 and 6 months, respectively, which were maintained regardless of subsequent tamsulosin use. Conclusion: The partial or total withdrawal of tamsulosin after 1 year of 5-ARI, followed by combination therapy for 3 months, resulted in little or no deterioration of LUTS in men with BPH in the final 12 months of the study.

Dutasteride after 1 year (n = 63) Dutasteride + tamsulosin As-needed tamsulosin Baseline 3 months 6 months 9 months 12 months IPSS 19.80 11.76 11.30 12.07 11.31 Qmax 9.75 n/a 15.84 n/a 20.43

KEYWORDS: Dutasteride; Tamsulosin; Benign prostatic hyperplasia CORRESPONDENCE: Paul F Siami, MD, 3521 Lincoln Ave, Evansville, IN 47714 USA ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 93. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11

UroToday International Journal original study UIJ Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression Introduction METHODS

There is little doubt about the existence of benign prostatic Study Design hyperplasia (BPH) in men in the United States. Prevalence is at 40% in men 60 years of age and 90% for men 80 years or This single-site, open-label study included 63 men > 50 years of older [1]. Symptomatic BPH left untreated can progress to a age, with clinical diagnoses of BPH. Baseline assessments prior worsening of symptoms, obstruction, acute urinary retention, to beginning the study included eligibility criteria, medical infection, and the need for surgery [2]. Lower urinary tract history, physical exams (including digital rectal examination symptoms (LUTS) typically arise from the prostate or bladder. [DRE]), concomitant medication, hematology, serum chemistry, Symptoms are classified into obstructive or irritative, and they serum PSA, prostate volume by transrectal ultrasound (TRUS), can be rated on a scale, such as the International Prostate maximum urine flow (Qmax), post-void residue (PVR), urinalysis, Symptom Score (IPSS). Currently, there are 2 drug classes with adverse events, BPH symptoms (IPSS), AUR (surgery/resource different mechanisms of action, which are the mainstay of the utilization), BPH impact index (BII), and evidence of urinary medical management of BPH. One class is the alpha-antagonist tract infection (UTI). Those subjects meeting all inclusion and (α-blocker) and the second are the 5-alpha-reductase inhibitors exclusion criteria began combination therapy with 0.5 mg once (5-ARI). Efficacy with either agent as monotherapy has been daily of dutasteride and 0.4 mg once daily of tamsulosin for demonstrated in other trials [3,4]. The use of these 2 classes the first 3 months. Subjects then returned to the clinic every in combination therapy to control LUTS due to BPH has been 3 months, for the next 9 months, for symptom assessment, established in a number of studies [1,5]. dutasteride continuance counseling, and placement on flexible tamsulosin dosing on an as-needed basis according to symptom Barkin et al. have demonstrated that BPH symptom relief can be decline or improvement. maintained after withdrawal of the alpha-blocker tamsulosin from sustained combination therapy of dutasteride and At the 3-month study visit, concomitant medications, adverse tamsulosin. However, it has not been shown whether patients events, and vital signs were recorded. Subjects were questioned with BPH, who are at high risk for symptom progression and who for evidence of UTI, AUR, hematuria, and hematospermia, and achieve optimal improvement of symptoms on combination asked to complete the BII, PPSM, and IPSS. Any unused study therapy followed by withdrawal of the alpha-blocker, will medication was collected and counted, and a new 3-month maintain the degree of improvement relative to the continuous supply was dispensed. Subjects were counseled to: coadministration of the 2 agents. 1. continue dutasteride on a daily basis, The objective of this study is to look at men with BPH who 2. discontinue, taper, or restart their tamsulosin as symptoms are at a high risk for symptom progression and who achieve might dictate, and optimal improvement of symptoms on combination therapy 3. return to the clinic in 3 months. followed by withdrawal of the alpha-blocker. Will returning the alpha-blocker on an as-needed basis for symptom control At the 6-month study visit, the same assessments from the previous visit were again made, with the addition of PVR maintain the degree of improvement relative to the continuous and urine flowmetry. A new supply of study medications was coadministration of the 2 agents? dispensed, subjects were counseled to discontinue, taper, or restart their tamsulosin as symptoms might dictate, and return This study in men with moderate to severe symptomatic to the clinic in 3 months. Subjects were counseled to: BPH investigated the efficacy and safety of treatment with dutasteride (0.5 mg) once daily for 1 year and tamsulosin (0.4 1. continue dutasteride on a daily basis, mg), administered once daily for 3 months. Subjects were then 2. discontinue, taper, or restart their tamsulosin as symptoms counseled to begin flexible dosing of tamsulosin, if possible, might dictate, and taking it only on an as-needed basis, depending on the severity 3. return to clinic in 3 months. of symptoms and the clinical outcome.

At a 9-month study visit, concomitant medications, adverse events, and vital signs were recorded. Subjects were questioned for evidence of UTI, AUR, hematuria, and hematospermia, and asked to complete the BII, PPSM, and IPSS. Any unused study

UroToday International Journal original study UIJ Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression medication was collected and counted, and a new 3-month Table 1. Baseline characteristics. supply was dispensed. Subjects were counseled to: http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11t1

1. continue dutasteride on a daily basis, Baseline parameters Value* 2. discontinue, taper, or restart their tamsulosin as symptoms Age (years) 66.63 might dictate, and IPSS 19.8 3. return to the clinic in 3 months. PSA (nag/mL) 4.73 Subjects returned to the clinic at 12 months. Unused study Prostate volume 57.65 cc medications were collected and counted. Subjects were Qmax 9.75 ml/sec evaluated as before, which included hematology, chemistry, total serum PSA, PVR, and flowmetry. Subjects were thanked PVR volume 82.33 ml and discharged from study participation. *Unless otherwise noted, values are means.

LUTS were assessed at screening, baseline, and every 3 months using the self-administered IPSS questionnaire, including the BPH-related health status evaluation (question 8). PSA, hematology, and serum chemistries were performed at tamsulosin saved by those able to reduce or discontinue its usage. baseline, 6-month, and 12-month visits. Quality of life (QoL) Effectiveness was assessed using IPSS and Qmax, while quality of was assessed using the PPSM and BII every 3 months. Qmax life was measured by BII and PPSM. Safety was measured by UTI and PVR measurements were made at the initial screening, and AUR incidence and resource utilization. Pharmacoeconomic baseline, 6-month visit, and 12-month visit. TRUS was impact was calculated via direct tablet count. performed at the initial screening. Evidence for UTI, hematuria, and hematospermia was assessed every 3 months. Statistical Considerations Study Population This was an open-label, single-arm observational study. All subjects were included in the intent-to-treat population. Men > 50 years of age with a clinical diagnosis of BPH by medical The population was analyzed in 4 dynamic cohorts based on history and physical exam, including digital rectal examination, tamsulosin usage after 3 months of combination therapy. were enrolled in the study. Other entry criteria were IPSS > 12, prostate volume > 30 cc (TRUS), total serum PSA > 1.5 ng/ml, 1. No change in dose as initiated at baseline. Qmax > 5 and < 15 ml/second, minimum voided volume > 125 2. Increased or restarted tamsulosin after tapering or ml (based on 2 voids), and the ability to give informed consent discontinuing. and comply with the protocol for 1 year. Exclusion criteria were 3. Reduced tamsulosin dosage. total serum PSA > 10 ng/ml, history or evidence of prostate 4. Discontinued tamsulosin completely. cancer, previous prostate surgery, cystoscopic examination or catheterization within 7 days prior to screening, AUR within 3 The percent change in tamsulosin usage was based on the months prior to screening, post-void residual volume > 250 ml, actual amount used based on pill count. For IPSS, Qmax, and a history of breast cancer, any history or current use of drugs QoL assessments, the values and change from month 0 were that would enhance or diminish the action of the study drugs or compared at month 3, month 6, month 9, and month 12. the occurrence of side effects (including anabolic steroids), the use of phytotherapy for BPH, renal insufficiency, malignancy other than basal-cell carcinoma, hypersensitivity to any study RESULTS component, or participation in another study concurrently. Subject Demographics and Disposition Study Endpoints Sixty-three subjects were enrolled in the study and entered into the combination therapy phase. Fifty-four subjects completed The primary endpoints were to determine the proportion of the study, 6 subjects discontinued due to adverse events, 2 subjects who were able to discontinue tamsulosin without subjects withdrew consent, and 1 subject was lost to follow- deterioration of symptoms and the average amount of up (Tables 1 and 2). The mean age was 66 and the majority of

UroToday International Journal original study UIJ Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression Table 2. Baseline characteristics by final cohort. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11t2

Baseline characteristics of tamsulosin usage cohorts (12 month visit) Parameter No change Increased or restarted reduced dose Discontinued N 6 17 14 17 Age IPSS 22 (16-26) 22 (14-35) 19 (12-30 18 (12-30) Qmax 10.2 (7.3-13.7) 10 (5.7-14.8) 10.5 (6.1-14.8) 10.4 (5.4-18.4) PSA 6.5 (3.2-9.7) 4.4 (1.7-12.4) 4.9 (1.5-10.9) 4.2 (1.3-10.1) Prostate volume 61.7 (42.5-80.2) 62.6 (32.1-127.9) 57.6 (32.7-85.4) 51.2 (30-107.6) PVR 80.5 (10-237) 94.9 (52-218) 67.7 (5-176) 82.5 (22-200)

the patients were Caucasian. Mean baseline values for IPSS and Figure 1. Mean IPSS score by tamsulosin use. Qmax for all subjects were 19.80 and 9.75 ml/sec, respectively. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11f1

Effectiveness Endpoints

The mean total IPSS values after 3, 6, 9, and 12 months are represented in Table 3. All subjects had symptom improvement with the addition of tamsulosin; however, the symptoms appeared to be somewhat stable in all groups at 6 months, 9 months, and 12 months, regardless of tamsulosin usage (Figures 1 and 2). There was no clinically significant difference in the mean change from month 3 between groups at 12 months.

The 3-month combination of dutasteride therapy resulted in at least a 3-point improvement in IPSS scores, suggesting a meaningful improvement (Figures 1 and 2). After flexible dosing was initiated, the initial benefit was maintained across all groups, regardless of tamsulosin dosing. Figure 2. Mean IPSS change from baseline by tamsulosin use. Changes from baseline for Qmax and BII stratified by cohort http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10f5 are represented in Figures 3 and 4, respectively. As with IPSS, Qmax improvement achieved following tamsulosin dosing was maintained in all groups through 12 months. Similarly, BII changes were also maintained through month 12.

Cohorts were further stratified into 2 groups to see if prostate volume had any correlation with tamsulosin usage: subjects with PV 30 to 50 mL and subjects with PV > 50 mL. Median prostate size across all subjects was 48.8 mL. Due to the small size of this study, tamsulosin usage cohorts were combined into 2 groups: subjects who were able to reduce or discontinue

UroToday International Journal original study UIJ Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression Figure 3. Qmax changes from baseline by tamsulosin use. Figure 4. BII changes from baseline by tamsulosin use. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11f3 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11f4

tamsulosin usage, and subjects who either had no change or Table 3. Changes in mean values for IPSS and Qmax, for increased tamsulosin usage, respectively (Table 5). all subjects. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11t3 The Patient Perception of Study Medication (PPSM) questionnaire was evaluated case by case. While these patients Baseline 3 6 9 12 reported outcomes that were inconsistent across all measures months months months months in all cohorts, it appears to the investigator that trends were IPSS 19.8 11.76 11.3 12.07 11.31 consistent with the objective measures also employed in this Qmax 9.75 n/a 15.84 n/a 20.43 study.

Safety Profile and Tolerability

Tolerability has been well established in previous studies, in both monotherapy and combination regimens. Adverse events Table 4. Adverse events by body system. emergent in this study are reported in Table 4. Of 149 total http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11t4 adverse events reported, only 27 were designated as possibly or probably study-drug related: 8 had altered ejaculation, Number of patients with at least 1 adverse event, by body 4 had vertigo, 3 had fatigue, 2 had nasal congestion, 2 had system gynecomastia, 2 had erectile dysfunction, 2 had decreased Body system Total Drug related libido, 1 had urgency incontinence, 1 had headache, 1 had rash, and 1 had postural hypotension. Two subjects were discontinued Body as a whole 7 3 from study participation while the remainder completed the Cardiovascular system 18 1 study. No subjects experienced AUR that required utilization of Digestive system 9 1 resources, such as catheterization or surgery. Endocrine system 6 2 Six subjects experienced 11 serious adverse events but none Hemic and lymphatic system 0 0 were study related. There was 1 death, but the remaining Metabolic and nutritional disorders 2 0 subjects completed the study. Musculoskeletal system 18 0 DISCUSSION Nervous system 19 4 Respiratory system 31 1 Men with BPH often present with a wide constellation of LUTS Skin and appendages 15 2 that respond well to pharmacotherapy. Long-range studies Urogenital system 24 13 have demonstrated that both dutasteride and tamsulosin can

UroToday International Journal original study UIJ Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression Table 5. Number of patients in each cohort, further highest IPSS scores at baseline, and who had derived the divided by prostate volume. greatest benefit from adding tamsulosin, tended to stay on http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11t5 combination therapy or added tamsulosin after discontinuing at 3 months. This may have resulted from reluctance to discontinue PV = 30-50 mL PV > 50 mL symptom relief or the perception of symptoms returning after Reduced/discontinued 18 13 discontinuing combination therapy. Those subjects who were tamsulosin on dutasteride monotherapy at 1 year seemed to trend toward further improvement, but the sample size was insufficient to No change/increased 10 13 produce confirmatory results. No subjects experienced AUR or tamsulosin required utilization of resources for safety issues, underscoring the safety of all of the self-selected regimens.

CONCLUSION initiate rapid improvement and maintain that level of relief This study, while small in size, suggests that symptom relief for an extended period. We also know that combination in subjects with BPH may be maintained or improved with therapy provides enhanced symptom relief when compared dutasteride monotherapy following symptom optimization with to monotherapy. Unfortunately, the number of study-drug dutasteride and tamsulosin combination therapy for 3 months. related adverse events increase with combination therapy, as The limitations to this trial are it’s size and observational design. demonstrated in the combination of Avodart and tamsulosin Prostate volume may be a key clinical parameter to the use of (CombAT) trial. intermittent combination of tamsulosin and dutasteride. A larger prospective, statistically adequate, double blind placebo- Remarkably, all subjects maintained similar improvement from controlled study will be needed to corroborate our results. baseline at 1 year, regardless of whether the subject: References 1. made no change in tamsulosin usage as initiated at baseline, 1. Roehrborn CG, Siami P, Barkin J, et al. The effects of 2. restarted tamsulosin after tapering or discontinuing dutasteride, tamsulosin and combination therapy on tamsulosin, lower urinary tract symptoms in men with benign prostatic 3. reduced tamsulosin usage, or hyperplasia and prostatic enlargement: 2-year results from 4. discontinued tamsulosin completely. the CombAT study. J Urol. 2008;179(2):616-612. PubMed ; CrossRef These data suggest that: 2. Emberton M, Cornel EB, Bassi PF, et al. Benign prostatic 1. in patients whose symptoms are not adequately controlled hyperplasia as a progressive disease: a guide to the risk on a 5-ARI alone, the addition of tamsulosin shows an factors and options for medical management. Int J Clin additional benefit in symptom improvement, and Pract. 2008;62(7):1076-1086. PubMed ; CrossRef 2. after maximal improvement has been seen in combination therapy, individualization of the tamsulosin dose based 3. Kirby RS, Roehrborn P, Boyle P, Bartach G, et al. Efficacy upon the patient’s clinical status dosing might be possible and tolerability of doxazocin and finasteride, alone or (coadministration with dutasteride and tamsulosin or in combination, in treatment of symptomatic benign monotherapy with dutasteride). prostatic hyperplasia: The Prospective European Doxazocin and Combination Therapy (PREDICT) trial. Urology. Furthermore, analysis of tamsulosin usage by prostate volume 2003;61(1):119-126. PubMed ; CrossRef revealed that patients with smaller prostates (30 to 50 mL) were 4. Lepor H, Williford WO, Barry MJ, et al. The effects more likely to reduce or discontinue tamsulosin usage, whereas of Terazosin, finasteride, or both in benign prostatic patients with larger prostates (> 50 mL) had similar outcomes hyperplasia. Veterans Affairs Cooperative Studies across all cohorts. Benign Prostatic Hyperplasia Study Group. N Eng J Med. 1996;335(8):533-539. PubMed ; CrossRef We also observed that those subjects who started with the

UroToday International Journal original study UIJ Dutasteride with As-Needed Tamsulosin in Men at Risk of Benign Prostatic Hypertrophy Progression 5. McConnel JD, Roehrborn CG, Bautista OM, et al. The long term effect of doxazosin, finasteride, and combination therapy on clinical progression of BPH. N Engl J Med. 2003;349(25):2387-2398. PubMed ; CrossRef

6. Barkin J, Guimarães M, Jacobi G, et al. Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol. 2003;44(4):461-466. PubMed ; CrossRef

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.11 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Prevalence and Risk Factors Associated with Overactive Bladder

Christopher CK Ho, Teo Chee Yang, Phang Lay Fang, Nur Aziyana Noor Azizi, Farah Lyna Darwin, Nur Afifah Mohd Ghazi, Guan Hee Tan, Eng Hong Goh, Praveen Singam, Badrulhisham Bahadzor, Zulkifli Md Zainuddin Urology Unit, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia Submitted November 7, 2011 - Accepted for Publication November 23, 2011

ABSTRACT

Introduction: The pathophysiology and management of overactive bladder (OAB) has been the subject of intensive research, but the prevalence of OAB in the community has not been well documented. This study aims to determine the prevalence of OAB among men and women attending the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). This study also shows the impact of OAB on daily life activities and associated risk factors. Methods: Four hundred respondents, aged between 18 to 70 years and visiting UKMMC, were interviewed and scored using the validated OAB screener. Information on sociodemographic data, the effects of OAB on daily living activities, and possible risk factors were included in the questionnaire. Results: The prevalence of overactive bladder in the study population was 42%. The most common symptom complaint was nocturia (94%). Gender (p = 0.004) and family history (p = 0.016) were related to a higher prevalence of overactive bladder. Males were significantly affected with the odd ratio of 1.792 compared to females. Race, age, monthly income, occupation, family, and smoking history were not associated with OAB. The most commonly affected activity of daily living in OAB patients is sleep disturbance (43.5%). Conclusion: The study has shown that the prevalence of OAB is relatively high in the Malaysian community, especially among males, and those with a positive family history. This has warranted closer attention to the issue. Preemptive measures should be taken by health care givers, the government, and the community to raise OAB awareness among society.

Introduction bladder (OAB) as “urgency, with or without urge urinary incontinence (UI), usually associated with frequency and The International Continence Society (ICS) defines overactive nocturia” [1]. However, many studies have used different

KEYWORDS: Prevalence; Overactive bladder; Daily living activities; Risk factors CORRESPONDENCE: Christopher CK Ho, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 88. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder definitions of OAB in their results, which have made comparisons across studies difficult, and the prevalence rates have differed OAB can be treated, which involves behavioral therapy, widely [2-6]. physiotherapy, and pharmacotherapy. Most clinicians would start treatment by physiotherapy through bladder Using the ICS definition, a study among Asian men in11 training, which is a reasonable first-line therapy. However, countries found that the estimated prevalence of OAB among pharmacotherapy allows the patient to improve more rapidly. men was 29.9% [7], whereas another study done on women Anticholinergic drugs are the main pharmacotherapy agents, showed the prevalence of OAB was 54.1% [8]. Also, from these such as oxybutynin and tolterodine. A study was conducted 2 studies, it was found that OAB was more common among to determine the effectiveness of anticholinergic drugs in the professional workers (43%), high-income groups (26%, income treatment of OAB. Results have shown that anticholinergics of > RM 2660), and urban dwellers (64%). With increased age, produce significant improvements in OAB symptoms; however, there was an increased incidence of OAB; i.e., the prevalence the effectiveness of these drugs is still unclear [20]. was 53% in men aged > 70 years [7,8]. Other than that, there is a significant relationship between OAB and a positive family The general objective of this research was to study the history [7,8]. epidemiology of overactive bladder among men and women attending UKMMC. Our specific objective was to determine A study was conducted on the role of nicotine in the micturition the prevalence of OAB in the population in UKMMC, the reflex in rats. It was found that nicotine had significant sociodemographic and health-related attributes in this stimulation on the nicotinic acetylcholine receptors on bladder population, the impact on activities of daily living in OAB activity [9]. Another population-based study done in Finland patients, and, last but not least, to identify the risk factors showed that a history of smoking may increase the risk of lower associated with OAB. urinary tract symptoms, with the odds ratios of 1.39 and 1.34 for current and former smokers, respectively, compared to men MATERIALS AND METHODS who never smoked [10]. However, additional research on the association of smoking and OAB needs to be done to establish The Research and Ethical Committee, Faculty of Medicine, this possible linkage more clearly. University Kebangsaan, Malaysia (FF-291-2010), approved this research. OAB has a significant impact on the quality of life of men who are affected by disturbing urinary symptoms [11,12]. Wagner et This is a cross-sectional, face-to-face, community-based survey. al. (2002) also reported a significant association between OAB It was conducted in all the clinics, the main lobby, the visitor’s and urinary tract infection, fall injuries, and more frequent lobby, and all the departments in UKMMC, except the urology visits to their physicians [13]. In the NOBLE study, Stewart et al. clinic. Private rooms were sought in the designated locations (2003) found that OAB has a significant impact on quality of life, to ensure respondent confidentiality. The fieldwork took quality of sleep, and mental health, in both men and women 4 months. The respondents were men and women, aged [5]. Studies have found that most people with OAB used non- between 18 to 70 years, coming to UKMMC. They were patients medical coping strategies and would like to speak with a health from all clinics, the relatives of the patients, and the staff of care provider about their disturbing symptoms [14,15]. UKMMC (except the urology clinic). Two hundred men and 200 women were randomly selected for this study (convenience The pathophysiology and management of OAB has been the sampling). Patients, relatives, and staff in UKMMC who refused subject of intensive research, but the prevalence of OAB in the to participate; those unable to respond to the questionnaire community has not been well documented [16,17]. Published accordingly; those who have other obvious pathological reports on the effects of OAB on quality of life are also limited problems, such as urinary tract infection, stones, BPH, etc.; [10], suggesting that OAB is generally under-diagnosed and or patients who are being treated in the urology clinic were under-treated [18]. Globally, except for a European report [19], excluded from this study. there has been no comprehensive epidemiological survey on OAB. We, therefore, aim to conduct a population-based study The diagnostic criteria of OAB was based on the International in a multiethnic population in Malaysia and determine the Continence Society (ICS) definition of OAB: “OAB is urgency, prevalence of OAB in men and women. We also study how OAB with or without urge urinary incontinence (UI), usually affects the activity of daily living in this group and if there are associated with frequency and nocturia after the exclusion of any associated sociodemographic and health-related attributes. any obvious pathology such as infection or stones.”

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder Table 1. Frequency distribution of study population, We used the questionnaires from the OAB screener—OAB-V8 according to gender. study—and collected data on the symptoms of urgency, http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t1 frequency, nocturia, and urge urinary incontinence, and how each of these symptoms bothered them. Having the score of Gender n % 8 or greater indicated that the respondent had overactive Male 207 51.8 bladder. For sociodemography, health status, and daily living activity disturbance, a questionnaire was designed to document Female 193 48.3 the participants’ sociodemographic data; e.g., age, gender, Total 400 100 race, etc.).

The questionnaire was self-administered by the respondents who were assisted by medical students, when necessary. During the face-to-face interview, written consent was obtained from the respondents. Table 2. Frequency distribution of study population, according to age group. The prevalence of OAB symptoms (urgency, frequency, nocturia, http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t2 and urge incontinence) was described in percentages. The association between these symptoms and the sociodemographic Age group (years) n % data and health status were analyzed using the chi-square 18-30 110 27.5 test. All data were entered and analyzed using the Statistical 31-45 101 25.3 Package for the Social Sciences (SPSS), version 19, and OpenEpi (www.openepi.com/OE2). 46-60 143 35.8 61.70 46 11.5 RESULTS Total 400 100

Study Population Demographics

A total of 400 respondents, comprised of men and women aged between 18 to 70 years who fulfill the inclusion criteria, were included in the survey. The mean age for men and Table 3. Frequency distribution of study population, women was 40.3 ± 8.3 and 38.6 ± 7.4 years, respectively. Table according to race. 1 shows the distribution of the study population according http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t3 to gender. Although each age group was well represented (Table 2), the majority (35.8%) was in the middle-age group Race n % (46 to 60 years). Table 3 shows the distribution of the study Malay 319 79.8 population according to race. Most of the respondents were Chinese 53 13.3 nonprofessionals (35.3%) and the unemployed (32.0%) (Table 4). Most of the respondents were from a low socioeconomic Indian 24 6 group with 36.0% (144/400) at a monthly income less than RM Other 4 1 500 (Table 5). Among the 193 respondents who were parous, Total 400 100 the majority had had 1 to 4 childbirths (49.2%) (Table 6).

Prevalence of Overactive Bladder

The prevalence of overactive bladder in the study population was 42% (168/400). The distribution of the OAB population, patients (94.0%). according to the questions asked in the OAB-V8 screener, is shown in Table 7. It was noted that question 5, about nighttime Factors Related to the Occurrence of Overactive Bladder urination, was the most common complaint among OAB

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder Table 4. Frequency distribution of study population, Table 7. Frequency distribution of study population, according to occupation. according to questions. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t4 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t7

Type of occupation n % Questions n = 168 % Professional 78 19.5 Q1. Frequent urination during daytime? 140 83.3 Nonprofessional 141 35.3 Q2. An uncomfortable urge to urinate? 100 59.5 Retiree 53 13.3 Q3. A sudden urge to urinate with little or 103 61.3 Unemployed 128 32 no warning? Total 400 100 Q4. Accidental loss of small amounts of 76 45.2 urine? Q5. Night-time urination? 158 94 Q6. Waking up at night because you had 150 89.3 to urinate? Table 5. Frequency distribution of study population, Q7. An uncontrollable urge to urinate? 88 52.4 according to monthly income. Q8. Urine loss associated with a strong 87 51.8 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t5 desire to urinate?

Monthly income (RM) n % < 500 144 36 501-1500 90 22.5

1501-2500 82 20.5 Gender and family history were significantly related to a higher 2501-3500 45 11.3 prevalence of OAB. Race, age, monthly income, occupation, > 3500 39 9.8 smoking, a history of pelvic surgery, radiotherapy, and constipation were not associated with the occurrence of OAB Total 400 100 (Table 8).

Gender: There was a significant relationship between gender and a prevalence of OAB (p = 0.004). The majority of the population with OAB was male. The odds of having OAB among males were 1.8 times more than females. Table 6. Frequency distribution of study population, according to parity. Ethnicity: Ethnicity (Malays versus non-Malays) was not http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t6 significantly related to the prevalence of OAB inthe Number of births n % Malaysian community (p = 0.996). Nulliparious 75 38.9 Age: The age of the respondents was divided into 4 groups 1-4 95 49.2 (18 to 30 years old, 31 to 45 years old, 46 to 60 years old, > 5 23 11.9 and 61 to 70 years old). The result showed that age was considered an insignificant risk factor for OAB (p = 0.125). Total 193 100

Monthly Income: The result showed that monthly income, which implies the socioeconomic status of the respondents, was insignificant as a risk factor of OAB (p = 0.078).

Occupation: Occupations of the respondents, which were divided into professional, nonprofessional, retiree, and

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder Table 8. Demographic factors and their relation to the occurence of OAB. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t8

Factor OAB p value Odds ratio 95% Confidence interval Yes No Ethnicity Malay 134 (42%) 185 (58%) 0.996 1.001 0.611-1.641 Non-Malay 33 (40.7%) 31 (59.3%) Gender Female 67 (34.7%) 126 (65.3%) 0.0004 1.792 1.198-2.680 Male 101 (48.8%) 106 (51.2%) Age 18-30 45 (40.9%) 65 (59.1%) 0.125 1.250 (18-30 vs 31-45) 0.716-2.182 31-45 36 (35.6%) 65 (64.4%) 0.744 (31-45 vs 46-60) 0.440-1.259 46-60 61 (42.7%) 82 (57.3%) 0.572 (46-60 vs 61-70) 0.293-1.119 61-70 26 (56.5%) 20 (43.5%) Monthly income (RM) < 500 64 (44.4%) 80 (55.6%) 0.078 0.8 (< 500 vs 501-1500) 04718-1.356 501-1500 45 (50%) 45 (50%) 1.412 (501-1500 vs 1501-2500) 0.7724-2.58 1501-2500 34 (41.5%) 48 (58.5%) 1.417 (1501-2500 vs 2501-3500) 0.6627-3.028 2501-3500 15 (33.3%) 30 (66.7%) 1.45 (2501-3500 vs > 3500) 0.5613-3.746 > 3500 10 (25.6%) 29 (74.4%) Occupation Professional 28 (35.9% 50 (64.1%) 0.113 0.8014 (professional vs nonprofessional 0.4526-1.419 Nonprofessional 58 (41.1%) 83 (58.9%) 0.5357 (nonprofessoinal vs retiree) 0.2829-0.1014 Retiree 30 (56.6%) 23 (43.4%) 1.906 (retiree vs unemployed) 0.9976-3.643 Unemployed 52 (40.6%) 76 (59.4%) Family history Yes 38 (55.1%) 31 (44.9%) 0.016 1.895 1.123-3.198 No 130 (39.3%) 201 (60.7%) Smoking Yes 37 (50%) 37 (50%) 0.122 1.489 0.897-2.741 No 131 (40.2%) 195 (59.8%) Pelvic surgery Yes 27 (35.1%) 50 (64.9%) 0.170 0.697 0.416-1.169 No 141 (43.7%) 182 (56.3%) Radiotherapy Yes 4 (66.7%) 2 (33.3%) 0.217 2.805 0.508-15.495 No 164 (41.6%) 230 (258.4%) Constipation Yes 40 (48.8%) 42 (51.2%) 0.163 1.414 0.868-2.302 No 128 (40.3%) 190 (59.7%) Parity Nulliparous 32 (40.5%) 47 (59.5%) 0.229 1.362 (nulliparous vs 1-4) 0.7341-2.526 1-4 32 (33.3%) 64 (66.7%) 1.8 (1-4 vs > 4) 0.6126-5.289 > 4 5 (21.7%) 18 (78.3%)

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder Table 9. Frequency distribution of population with OAB that the insignificance of parity was a factor related to the according to changes in activity of daily living (ADL). occurrence of OAB among female respondents (p value = http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06t9 0.229).

Activity of daily living Affected (%) Not affected (%) Activity of Daily Living (ADL) in OAB Patients Sleep interrupted 73 (43.5) 95 (56.5) The most common complaint affecting the activity of daily Intimate relationship 32 (19) 136 (81) living of OAB patients (Table 9) was sleep disturbance (43.5%). with spouse Workplace performance 38 (22.6) 130 (77.4) DISCUSSION Travelling hindrance 29 (17.3) 139 (82.7) Personal hygiene 38 (22.6) 130 (77.4) Currently, there are multiple screening tools used for the diagnosis of OAB internationally. In our current research, the Social life 28 (16.7) 140 (83.3) questionnaire adopted was based on OAB-V8, which has been Self-esteem 22m(13.1) 145 (86.9) validated for use in a primary care setting to diagnose OAB. It was designed and refined by Coyne KS et al. to determine how troubled the respondents are by bladder symptoms [21]. A patient can self-score his or her level of inconvenience and determine whether or not to approach his or her physician unemployed, were insignificant risk factors for OAB (p = regarding possible treatment options. Having the score of 8 or 0.113). greater indicates that the respondent is having OAB.

Family History: A positive family history of bladder The prevalence of OAB in the study population was 42% dysfunction was significant among OAB respondents (p (168/400). We found that the prevalence of OAB in Malaysia value = 0.016). The odds of having OAB in those with a was 4 times higher than that reported by Irwin et al. in their positive family history were 1.9 times higher compared to population-based survey of 5 countries [22]. Their study found those without. that the overall prevalence of OAB was only 11.8%. This could be attributed to the different methodology adopted for data Smoking: A smoking background was an insignificant risk collection and our multiracial composition in Malaysia. Irwin et factor among OAB respondents (p value = 0.122). However, al. used a population-based, cross-sectional telephone survey the odds of smokers having OAB were 1.5 times higher than in 5 countries, which differed from our validated questionnaire nonsmokers. of a face-to-face interview with respondents in UKM. Also, the small sample size of 400 we chose also may have contributed Pelvic Surgery: Results showed that a history of pelvic to the difference. Through the current survey, the recognition surgery was insignificant in OAB respondents (p value = of OAB among the population was minimal. This was probably 0.170), and the odds of having OAB among those who had due to poor dissemination of information by the mass media a previous surgery were 0.7 compared to those without any and social stigma. Poor education and inaccessibility to medical history of surgery. care are also contributing to underreporting of OAB.

Radiotherapy: The majority of OAB respondents did not The symptoms are the most important element for the diagnosis have a significant history of radiotherapy (p value = 0.217). of OAB. Hence, all our OAB respondents were diagnosed based The odds ratio of OAB among those having radiotherapy on symptoms that constitute urgency, frequency (daytime and exposure compared to those without radiotherapy was 2.8. nighttime), and urge urinary incontinence. Cheung WW et al., in their study on the prevalence of OAB among male urologic Constipation: Difficulty in passing motion was not a veterans, found that 95% reported urinary frequency and 85% significant risk factor of OAB (p value = 0.163), with the nocturia [23]. However, another study by Lapitan MC et al., on odds ratio of 1.4. the epidemiology of OAB among females in Asia, found that the most common symptom was urgency, which was present in 65.4%, followed by frequency (55.4%) [8]. Our findings Parity: The number of parity was divided into 3 groups concurred with Cheung WW et al., where the highest symptom (nulliparous, 1 to 4, and more than 4). Results showed

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder complaint among OAB patients was nocturia [23]. as relevant smoking history and childbirth history, among others [7,8]. A genetic locus (D13S171) was found in patients A study by Stewart WF et al., conducted in a US population, with detrusor overactivity (DO) or OAB phenotypes in a study showed that the overall prevalence of OAB was similar between revealing its genetic linkage in Australia and the United men (16.0%) and women (16.9%) [5]. A study conducted in Kingdom [26]. A positive family history of OAB symptoms was Venezuela showed females were more affected than males evident and proved significant in this study (p = 0.016, OR= (25.6% in women versus 13.7% in men, p < 0.005) [24]. A study 1.895), therefore suggesting a possible genetic predisposition. conducted in the US (New York) shows that OAB was present in However, more studies should be done to validate this theory. 60.5% of men and 48.3% of women (p = 0.058) [23]. Our finding was somehow consistent with the latter where there was a In a study on the roles of central and peripheral nicotinic significant relationship between gender and the prevalence of receptors in the micturition reflex in rats, nicotinic acetylcholine OAB, with the majority of the OAB population being male. The receptor activation of the C-fiber afferent nerves in the bladder odds of having OAB among males were 1.8 times more than induces detrusor overactivity. Other than that, the receptors females. in the spinal cord and brain have an excitatory and inhibitory effect on the bladder, as well, indicating that there is influence The previous study has shown that increased age is a strong on the bladder lining from nicotine exposure [9]. Yet, smoking risk factor associated with OAB, and it has been proposed that history was insignificant in our study (p = 0.122, OR = 1.489). It this is due to decreasing bladder capacity, estrogen deficiency, may be due to the sample distribution of the male-to-female degenerative neuronal control, and connective tissue changes as ratio being about 0.5. The smoking prevalence rate was age progresses [8,25]. This finding is supported by the National higher among Malaysian males compared to women (49.2% Overactive Bladder Evaluation (NOBLE) study, which showed compared to 3.5%, respectively) in a study where 4 countries that the prevalence of OAB symptomatology increases with age (Singapore, the Philippines, Vietnam, and Malaysia) were in both men and women [8]. However, we found that the age explored pertaining to gender and tobacco issues. Therefore, of the respondents was considered an insignificant risk factor our results may be biased in that only the male respondents for OAB. Surprisingly, there was evidence of a decreasing trend have a significant influence on smoking history [27]. in OAB patients as age increases, suggesting that somehow, with increasing age, one may have protective factors toward Studies have shown that prior pelvic and reconstructive OAB. Unfortunately, up to date, there is no specific research surgeries may denervate the bladder [28,29]. Patients who being done on this pattern, and the reason is unknown. One underwent a hysterectomy may experience OAB symptoms of the limitations from our research was that the number of postoperatively due to the disruption of autonomic nerve fibers respondents from each age group was not evenly distributed running along the pelvic plexus. However, this pathophysiology and bias of the result may exist. is not well understood, and most studies only involved women post hysterectomy or post pelvic organ prolapse (POP) surgery. So far, there was no research done to investigate the influence Therefore, this opens a new opportunity to study pelvic surgeries of ethnicity towards OAB. In Malaysia, there was no specific as a predictive factor of OAB in both genders. Nevertheless, research done to compare the 3 main races, namely the prior pelvic surgery was found insignificant in our study (p = Malay, Chinese, and Indian population. It was found that the 0.170, OR = 0.697). difference between the prevalence of OAB among the ethnic groups (Malay versus non-Malay) was insignificant (p = 0.996, There was no evidence of radiotherapy being a significant OR = 1.001). The relationship between overactive bladder with risk factor in causing OAB symptoms (p = 0.217, OR = 2.805). occupation and monthly income were also insignificant. The Though researchers have investigated the possibility of result was similar with the outcome of the study conducted on pelvic radiotherapy effects on the bladder causing urinary Asian women [8]. However, the odds ratio for monthly income incontinence [35], there is not yet a definitive pathophysiology showed an increasing trend. This pattern was consistent with a to this condition. Therefore, more objective research should be study done on Asian men, which reported a higher incidence done, specifically to evaluate this risk factor. of OAB in the high-income group [7]. This might be related to their awareness towards OAB symptoms, as well as the need to There was no clear evidence to relate constipation as a risk seek treatment among this group. factor to OAB (p = 0.163, OR = 1.414). However, other studies have revealed its significant occurrence with OAB, which Previous studies have related many risk factors to OAB, such further exacerbate the symptoms [30-32]. This is due to a shared

UroToday International Journal original study UIJ Prevalence and Risk Factors Associated with Overactive Bladder pathophysiology, a side effect of the antimuscarinic drugs in 25% produces a significant improvement in urgency, frequency, treating OAB, or due to dietary reasons in order to control the and nocturia [36]. OAB symptoms. Along with poor fluid intake, constipation has been a common complaint among OAB patients. CONCLUSION

Research has been conducted, revealing multiparity (parity The study has shown that the prevalence of OAB is relatively of > 4) as a risk factor in causing OAB symptoms, and that high in the Malaysian community, especially among males and multiparous women were 1.5 times more at risk than the those with a positive family history. This has warranted closer nulliparous, or those with only 1 pregnancy [8]. Even so, in this attention to the issue. Preemptive measures should be taken current study, there was no evidence of parity being significant by the health care givers, the government, and the community in OAB (p = 0.229), though it was found that there is a trend to raise awareness of OAB among society. Among the effective increase with a parity increase (OR nulliparous versus a parity of measures proposed are the incorporation of OAB knowledge 1 to 4 = 1.362, and OR parity of 1 to 4 versus multiparous women in curricular education, better coverage by the mass media, = 1.8). It is said that childbearing and childbirth may damage improvement in health care policy, and better education of the peripheral nerves in the pelvis, resulting in a hyperactive the public by health care workers. Meanwhile, more studies bladder [33,34]. However, subjects were randomly approached should be done to further prove risk factors associated with the in this study, with 198 female respondents. Of those, 69 were occurrence of OAB in Malaysia. positive for OAB. Among those who were positive, only 5 were multiparous (7.25%). Thus, the majority of female subjects were References either considered nulliparous, 32/69 (46.38%), or with parity < 5, also 32/69 (46.38%). This has a significant impact on the 1. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten aforementioned factor and, therefore, may not be applicable U, et al. The standardization of terminology of lower in its validity. urinary tract function: report from the Standardization Sub-committee of the International Continence Society. The impact of OAB in daily life has been emphasized in several Neurourol Urodyn. 2002;21(2):167-178. PubMed ; CrossRef studies. Wagner et al. reported a significant association between OAB and urinary tract infection, fall injuries, and 2. Corcos J, Schick E. Prevalence of overactive bladder and frequent visits to physicians [13]. In the NOBEL study, Stewart incontinence in Canada. Canadian J Urol. 2004;11(3):2278- WF et al. found that OAB has a significant impact on the 2284. PubMed quality of life, quality of sleep, and mental health in both men and women [5]. In this study, the impact on sleep, intimate 3. Homma Y, Yamaguchi O, Hayashi K, Neurogenic relationships with spouses, workplace performance, travel, Bladder Society Committee. An epidemiological survey personal hygiene, social life, and self-esteem in OAB patients of overactive bladder symptoms in Japan. Br J Urol. was brought to attention. Most patients complained that sleep 2005;96(9):1314-1318. PubMed ; CrossRef disturbance had the most troublesome impact (43.5%). This was consistent with the aforementioned nocturia symptoms 4. Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein as the most bothersome among OAB patients. The impact on AJ. How widespread are the symptoms of an overactive ADL was followed by a change in workplace performance and bladder and how are they managed? A population-based personal hygiene, which equaled 22.6% for both. In regards to prevalence study. Br J Urol. 2001;87(9):760-766. PubMed the impact of the remaining factors: intimate relationships with spouse were 19%, travelling hindrance was 17.3%, social life 5. Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog was 16.7%, and, lastly, self-esteem was 13.1%. AR, Corey R, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20(6):327- Other factors that have not been analyzed in this study are the 336. PubMed volumetric fluid intake, as well as dietary issues. An increased fluid intake will result in increased urine production. This will 6. Temml C, Heidler S, Ponholzer A, Madersbacher S. cause frequency, as well as nocturia. Besides that, certain Prevalence of the overactive bladder syndrome by applying drinks, such as alcohol and caffeine, have diuretic effects that the International Continence Society definition. Eur Urol. will result in OAB symptoms, such as frequency and nocturia. 2005;48(4):622-627. PubMed ; CrossRef Indeed, it has been shown that the reduction of fluid input by

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©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.06 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil

Rógerson Tenório de Andrade,1 Marina de Andrade Lima Arcoverde,2 Fábio Oliveira Vilar,1 Misael Wanderley Santos Jr,1 Nicodemos Teles Pontes Filho,3 Salvador Vilar Correia Lima1 1Department of Urology, Federal University of Pernambuco, Recife, Brazil 2Federal University of Pernambuco, Recife, Brazil 3Post-graduation Program of Pathology, Federal University of Pernambuco, Recife, Brazil Submitted September 27, 2011 - Accepted for Publication December 9, 2011

ABSTRACT

Introduction: Penile cancer is a malignant disease that has an uneven geographical distribution. Brazil is one of the countries with the highest incidence of penile cancer, although epidemiological studies are rare. Poor hygiene, the presence of phimosis, HPV infection, and low socioeconomic status seem to be some important risk factors. The objective of this study is to know the clinical and epidemiological data on new cases of penile cancer in the state of Pernambuco, located in the northeast region of Brazil, and contribute to the national study of the Brazilian Society of Urology. Methods: We selected from a plethora of new penile cancer cases diagnosed from August 2008 to June 2009, at the department of urology of 5 referral hospitals of the National Health System. Interviews were conducted with a clinical, epidemiological questionnaire adapted from the questionnaire used by the SBU in the first epidemiological study of penile cancer. All patients gave written, informed consent for inclusion in the sample. This study was approved by the ethics committees of the institutions involved. Results: In 11 months of the study, 32 new cases of penile cancer were enrolled and analyzed in 5 referral hospitals in Pernambuco. The average age of lesion diagnosis was 59.2 years (SD ± 14.3 years), with 50% of cases diagnosed in patients over 60 years. Regarding schooling, 92% were illiterate or had only a primary level of schooling, and none advanced beyond the second grade. Assessing the antecedents and habits, it was found that 8 patients (32%) had at least 1 case of a lifelong STD, 14 patients (56%) reported a history of phimosis, and only 4 (16%) underwent circumcision, 3 of which during adulthood. Smoking was an addiction reported by 56.2% of patients. The average time between the appearance of the lesion and the diagnosis of penile cancer was higher than 10 months. Conclusion: Penile cancer in referral hospitals of Pernambuco usually involves men older than 60 years, with low education, a history of smoking, uncircumcised genitalia, and with delayed access to specialized medical care. It is necessary to create campaigns for the prevention and guidance of this most affected population.

KEYWORDS: Circumcision; Epidemiology; Penile cancer; Phimosis; Risk factors CORRESPONDENCE: Marina de Andrade Lima Arcoverde, Federal University of Pernambuco, Recife, Brazil (marinaarcoverde@ gmail.com). CITATION: UroToday Int J. 2012 Feb;5(1):art 91. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.09

UroToday International Journal original study UIJ Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil Introduction rates, but quite similar to both north and northeast regions of Brazil where this type of cancer is mostly located [3]. Therefore, Penile cancer is a malignant disease that has a curiously uneven the primary objective of this study is to analyze the clinical geographical distribution [1]. In Europe, the incidence is rare, and epidemiological profile of penile cancer in Pernambuco, and varies between 0.1 and 0.9 per 100 000 males. In the US, contributing to the Brazilian epidemiological tracing initiated it varies between 0.7 and 0.9 per 100 000 males. However, the by the Brazilian Society of Urology, and also to prove the under- incidence of penile cancer is significantly higher when dealing reported cases of penile cancer in the state in Pernambuco in with developing countries in regions such as Africa, Asia, and that previous study. The outcome data, such as disease-specific South America, where it can reach 20 per 100 000 males [2]. survival rate, type of surgery performed, and functional In these countries, penile cancer remains a major public health outcomes, does not meet the interest of this work. issue since it represents 10 to 20% of all malignancies in men [2]. METHODS

Penile cancer represents approximately 2 percent of all cancers This work was carried out in Pernambuco State, located in males in Brazil, with most cases reported in the north and in the northeast region of Brazil, through a multicenter the northeast regions [3]. In these areas, penile carcinoma study conducted in 5 referral hospitals, for the treatment of outnumbers, in some states, even the cases of prostate and urological cancer in the state; all 5 were part of the National bladder cancer [4]. Although the etiology of cancer is unknown, Health System. poor hygiene, the presence of phimosis, HPV infection, and low socioeconomic status are known risk factors [5]. Age is one of We studied every new case of penile carcinoma diagnosed and the main risk factors while ethnicity is not [6,7]. admitted in the urology services of these institutions, from August 2008 to June 2009, representing a total of 32 patients. We excluded from the study all patients diagnosed with Phimosis is present in 75 to 90% of penile cancer cases [8]. disease at a stage of premalignancy, those with inconclusive The incidence of penile cancer is extremely low, reaching less histopathological examinations, as well as those who refused than 1 percent of all diagnosed cancers, in countries where to participate. The hospitals’ protocols on penile cancer were circumcision is a common practice [6]. The prophylactic effect followed properly. of circumcision in penile carcinoma appears to be related to less retention of the smegma that has, arguably, a carcinogenic and Through an interview with the selected patients, we filled out inflammatory effect in animals [9]. a clinical, epidemiological questionnaire, adapted from the questionnaire used by the Brazilian Society of Urology in the Another factor that may predispose the development of penile first epidemiological study of penile cancer [3]. carcinoma is HPV infection. In some reports, the association between penile cancer and HPV reaches over 30% of the The variables in the questionnaire were age, education level, patients, revealing the oncogenic effect of the virus, also in a history of STD or preneoplastic disease, a partner with a men [7,10]. Other skin lesions, such as Queirat erythroplasia, history of HPV infection or cervical cancer, smoking, a history of Bowen’s disease, and balanitis xerotic, can also develop into phimosis and/or performing circumcision, the time between the squamous cell carcinoma (SCC) in the penile region [11], the appearance of the lesion and the diagnosis, site of the lesion, first 2 already considered by some authors as carcinoma in situ and histology. since they are composed of dysplastic characteristic cells [12]. Age was a categorical factor in this research, divided by Some studies reveal that SCC is the most common type of penile decades of life. Schooling was divided into illiterate, primary cancer, accounting for more than 95% of the cases [11, 23]. education (elementary and middle school), secondary Penile cancer primarily spreads through the lymphatic system. education (high school), and tertiary education (college and Inguinal lymph nodes are usually the first site of metastasis university). For patients who underwent circumcision, it was [11]. The treatment is mainly surgical, which may be a simple classified according to when the surgery took place (childhood, resection, partial, or complete amputation and emasculation adolescence, or adulthood). The lesion was classified according [6]. to the involvement of the region, such as glans; foreskin; shaft; base; glans and foreskin; glans, foreskin, and shaft; or the entire Recife, the capital of Pernambuco, has a penile cancer incidence of penis. According to the histological differentiation, the lesions 6.8/100 000 [13], which is higher than American and European

UroToday International Journal original study UIJ Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil Table 1: Distribution of cases by age group and level of Table 2: Characteristics of background and lifestyle. schooling. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.09t2 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.09t1 Patient N % Age group N % History of STD 21-30 1 3.1% None 17 53% 31-40 1 3.1% 1 episode 7 22% 41.50 9 28.1% 2 or more 4 12.5% 51-60 5 15.7% DNA 4 12.5% 61-70 9 28.1% Premalignant disease 1 3.1% > 70 7 21.9% Condylomatosis 3 9.4% School level N % Phymosis 19 59.4% Illiterate 5 15.6% Circumcision Primary education 24 75% Uncircumcised 28 87.5% Secondary 3 9.4% Childhood 1 3.1% education Adulthood 3 9.4% Total 32 100% N = Number of patients Smoking Nonsmoker 14 43.8% Smoker 18 56.2% Up to 20 years 3 16.7% > 20 years 13 72.3% were classified between grades I, II, III, and IV, the last being the DNA 2 11% greatest degree of undifferentiation. Partner The results were analyzed with descriptive statistics and Cervical cancer frequencies using the program BioEstat 5.0 for Windows. Absent 14 43.8% This work was approved by the ethics committees of all the DNA 18 56.2% institutions involved, and all patients gave written, informed consent for inclusion in the sample. HPV infection Present 1 3.1% RESULTS Absent 9 28.1% DNA 22 68.8% In 11 months of the study, 32 new cases of penile cancer were N = Number of patients admitted to referral hospitals in Pernambuco, of which 16 DNA = Did not answer (50%) were registered in the Cancer Hospital of Pernambuco.

The average age of affected patients was 59 years (SD ± 14.9 years), and the highest prevalence was found between the ages of 41 and 70 years old, representing a total of 71.9% of cases (Table 1). Regarding schooling, 91% of patients were found that 11 patients (33%) had had at least 1 case of STDs illiterate or had only studied until primary school. Those who throughout life. One of the patients had a prior diagnosis of had dropped out of school during the course of primary or preneoplastic disease (3.1%), and 3 others had been diagnosed secondary education were also included in these categories. with condylomatosis (9.4%). Only 1 patient reported a partner None of the respondents had initiated tertiary education. with a previous HPV infection (Table 2).

During evaluation of background and personal habits, it was Nineteen patients (59.4%) reported a history of phimosis,

UroToday International Journal original study UIJ Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil of which only 4 (12.5%) were circumcised. Smoking was an poor genital hygiene, and both are important factors in the addiction reported by 56.2% of patients, with an average of development of the disease [13]. The level of schooling in this 29.3 years of addiction for patients who smoke. study was used as a socioeconomic status meter and revealed that over 90% of patients had not exceeded the level of primary Regarding diagnosis, the average time between the appearance education. Since the northeast still has an illiteracy rate of of the lesion and the diagnosis of penile cancer was 10.8 months 18.7% [14], and one of the lowest incomes per capita in Brazil, (SD ± 2.08 months), and the sizes of the lesions ranged from 0.7 it is expected that this region contributes to a large portion to 10 cm, with an average 4.08 cm lesion. The most affected of total penile cancer in the country, which, according to the areas were the glans and/or the prepuce, representing a total Brazilian Society of Urology, corresponds to 40% [3]. There is 71.8% of cases. evidence that lack of hygiene in the genital region makes the individual more vulnerable to HPV infection, this being one The predominant histologic type was well differentiated SCC of the links between poor hygiene and penile cancer. On the (lesions I) found in 26 patients (81.25%), followed by the pattern other hand, it is notable that the socioeconomic-cultural status of moderately differentiated cell carcinoma (lesions II) in 2 interferes in the time between the onset of the lesion and patients (9.4%). Only 1 case had a diagnosis of mucoepidermoid the diagnosis, since people with low purchasing power have carcinoma. Another patient had a histopathological diagnosis greater difficulties accessing specialists, and they usually rely on of papillary hyperplasia, as well differentiated SCC, when the alternatives or popular therapies without proven effect. previous biopsy was diagnosed. A single patient had grade IV injury, with the presence of undifferentiated cells. Although the mechanism of action of HPV and other STDs in the formation of oncogenic cells is not fully elucidated, some studies In surgical treatment, there were 21 partial penectomies show a strong association between them [15]. HPV seems to (65.6%), 10 total penectomies (31.3%), and 1 circumcision act by altering the cell cycle by the expression of viral proteins (3.1%). that interact with cellular proteins. These cellular proteins disrupt the strict cell-cycle control by tumor suppressing genes, DISCUSSION which turns the infection into a strong precursor of tumors [7]. In our study, 34% of patients (n = 11) reported previous cases Brazil is one of the countries with the highest incidence of of unspecified STDs, while another 12.5% did not answer the penile cancer in the world, and even then, epidemiological question. Additionally, 9.4% of interviewed patients (n = 3) studies are rare. Recently, the Brazilian Society of Urology (SBU) reported the presence of condylomatous lesions in the penis. conducted a national study on penile cancer, aiming to outline In a study published in 2008, HPV-positive DNA was detected an epidemiological profile of the disease in the country [3] in 72% cases of penile carcinoma patients with squamous cell, and adopt preventive, diagnostic, and prophylactic measures. while in another study, the association between penile cancer In that study, Pernambuco contributed with only 1 case, for a and HPV infection was 30.5% [16]. It is important to remember total of 110 reported cases in 6 months across the country. Our that the data collected in our research was not confirmed research demonstrates that the occurrence of penile cancer in by laboratory tests, but still indicates the importance of the state of Pernambuco is much higher, making it clear that sexually transmitted diseases as a risk factor for penile cancer. they were underreported since there is notification of 32 new Furthermore, due to the low social-intellectual level of the cases in 11 months. patients, the use of a written questionnaire made it difficult to learn precise information about previous HPV infection, Penile cancer occurs more frequently in men after the sixth although, at the time, no patients had active HPV lesions. decade of life [6]. In the current sample, 50% of patients were over 60 years. Of the total cases analyzed, only 1 (3.1%) was Another identified risk factor was the presence of phimosis, aged 35 years, this incidence being significantly lower than found in 59.4% of our cases. Studies report that phimosis, as the 10% reported by Nardi [3]. On the other hand, a high well as chronic inflammation of the glans, increases the odds prevalence of penile cancer was noticed among the age group of developing penile cancer by 10 [17]. In turn, the practice of between 41 to 60 years, representing 43.8% of the total. This circumcision is a good way to prevent the neoplasm since it is emphasizes the importance of close monitoring of nonelderly performed soon after birth, decreasing the risk of developing patients with suspicious penile lesions. the pathology by 3 [18]; however, when performed later in adulthood, it does not offer the same protection [5]. In The low socioeconomic cultural status is closely related to our study, 4 patients had undergone circumcision as adults,

UroToday International Journal original study UIJ Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil and even then, the tumor took place, which agrees with the References literature. Although there is no data showing the relationship between personal hygiene, phimosis, and penile cancer, some 1. Barbosa Júnior AA, Athanázio PR, Oliveira B. [Cancer of scholars believe that good hygiene is the key to preventing the penis: study of its geographic pathology in the State both the development of phimosis and the tumor once they of Bahia, Brazil]. Rev Saúde Pública. 1984;18(6):429-435. are strictly related [2,19,20]. PubMed ; CrossRef

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©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.09 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access

Hammouda Sherif,1 Osama Abdelwahab,1 Abdelaziz Omar,1 Ibrahim Eraky2 1Urology Department, Faculty of Medicine, Benha University, Egypt 2Urology and Nephrology Center, Mansura University, Egypt Submitted November 4, 2011 - Accepted for Publication December 6, 2011

ABSTRACT

Aim: To evaluate PCNL in the supine position under ultrasound-guided puncture regarding its technical aspects, success rate, and complications. Patients and Methods: The study included 47 patients. All patients with renal and or upper ureteral stones were included in this study, while patients with uncorrectable coagulopathy congenital anomalies in the kidney were excluded. PCNL in the supine position was done under ultrasound-guided puncture while dilatation was done under fluoroscopy. Results: Twenty cases (42.5%) had pelvic stones, 18 cases (38.3%) had calyceal stones, 5 cases (10.6%) had multiple stones, 1 case (2.1%) had upper ureteic stones, and 3 cases (6.4%) had stagehorn stones. Twenty-five cases (53.2%) were right sided and 22 cases (46.8%) were left sided. Stone size was 2.9 ±1.029. Forty-two cases had radiopaque stones (89.4%), while 5 cases had radiolucent stones (10.6%). Upper calyceal puncture was done in 2 cases, middle calyceal puncture in 6 cases, lower calyceal puncture in 32 cases (68.1%), and multiple punctures in 9 cases. Stone disintigration using pneumatic lithoclast was done in 31 cases (66%), and in toto stone extraction was done in 16 cases (34%). The mean operative time was 70 minutes (60 to 120 minutes). The intraoperative complications were dilatation difficulties in 5 cases (10.6%) and bleeding requiring transfusion in 2 cases (4.2%). The stone-free rate was achieved in 44 cases (93.6%) and residual stones more than 4 mm were detected in 3 cases (6.4%). The mean hospital stay was 3.2 days (2 to 5 days). There was fever in 4 cases (8.5%) and urinary leakage in 3 cases (6.4%). Conclusion: PCNL in the supine position under ultrasound-guided puncture is feasible, safe, and successful, with minimal complications.

KEYWORDS: Supine position; PCNL; Stones Abbreviations and Acronyms CORRESPONDENCE: Hammouda Sherif, MD, Benha University, Benha Elgdeeda, Benha,11513, Egypt ([email protected]). CT: Computed tomography DJ: Double J CITATION: UroToday Int J. 2012 Feb;5(1):art 89. http://dx.doi. ESWL: Electrohydrolic lithotripsy org/10.3834/uij.1944-5784.2012.02.07 IVU: Intravenous urography PCS: Pelvicaliceal system PCNL: Percutaneous nephrolithotomy URS: Ureteroscopy US: Ultrasonography

UroToday International Journal original study UIJ Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access Introduction Figure 1. Position of the patient. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.07f1 Despite newer advances in stone surgery, including extracorporeal shockwave lithotripsy (ESWL) and flexible ureteroscopy (URS) with laser lithotripsy, the percutaneous approach is still the optimal method for minimally invasive, upper tract stone surgery [1]. Percutaneous nephrolithotomy (PCNL) in the prone position is accepted globally for its familiarity, excellent understanding of the anatomy in this position, and a reduced risk of visceral complications. However, there are various concerns regarding PCNL in the prone position, especially in the morbidly obese. Patients with compromised cardiopulmonary status and stature deformity are also not suitable for treatment in the prone position [2]. Moreover, in the conventional setting of the prone position, the hands of the urologists are in the field of the fluoroscopy, thus increasing the radiological hazards to medical personnel [3].Valdivia and associates [4] first described the supine position for percutaneous stone surgery. They suggested that the colon floats away from the kidney when the patient is in asupine position, which makes the colon less likely to be injured by a puncture made in the posterior axillary line. Hopper and colleagues [5] found that in a series of 90 prone and 500 supine necessary to wear a lead shield [8]. abdominal CT scans, the bowel was posterior to the kidneys in 10 and 1.9% of cases, respectively. They suggested that the In this study, we evaluated PCNL in the supine position under an bowel might be more often encountered in the posterior of the ultrasound-guided puncture in regards to its technical aspects, kidney in the prone position compared to the supine position. success rate, and complications. Therefore, performing PCNL in the prone position may increase the risk of colon injury. Patients and methods PCNL in the supine position has several advantages. First, it does not disturb blood circulation and respiration the way the This study included 47 patients (30 males and 17 females) prone position does. Second, the risk of iatrogenic colon injury admitted to the urology department of Benha University is lower in the supine position. Third, this position is convenient Hospital between January 2010 and December 2010. All for the anesthetist to observe the patient and switch to general patients with renal and or upper ureteral stones were included anesthesia with endotracheal intubation, if necessary. Fourth, in this study, while patients with uncorrectable coagulopathy, the angle between the horizontal plane and working tract is congenital anomalies in the kidney, such as a horseshoe kidney, small, so it is easier to wash out stone fragments through the and ectopic pelvic kidney were excluded. Informed written working sheath. In addition, urologists are made comfortable consent was taken from all participants after the study protocol by sitting while performing the operation [6]. was approved by the Research Ethical Committee, Faculty of Medicine, Benha University. Ultrasonography (US) has made a significant impact in the field of urinary interventions. US guidance makes procedures All patients where investigated preoperatively via routine safer, limiting the number of needle punctures and decreasing laboratory tests, pelviabdominal US, KUB, IVP, and spiral CT, radiation exposure. In most cases, it is complementary to when indicated. fluoroscopy, providing image guidance for different urinary procedures [7]. In addition to avoidance of contrast material PCNL in the supine position was done under high spinal administration, identification of all the tissue between the anesthesia, with the patient placed in the supine position skin and kidney and the energy expenditure of the surgeon with the side harboring the stone close to the operating table and other staff of the operating room decreases as it is not (Figure 1).

UroToday International Journal original study UIJ Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access The ipsilateral flank was elevated with a water bag, and the Figure 2. PCNL in the supine position. ipsilateral arm was laid on the thorax. Intravenous access http://dx.doi.org/10.3834/uij.1944-5784.2012.02.07f2` was established in the contralateral arm after a standard cystourethroscopy and a 6 Fr, open-tip, ureteral catheter was inserted into the ipsilateral ureteral orifice.

A kidney puncture was done under real-time US (Toshiba), after distending the pelvicalyceal system with saline from the ureteric catheter for better US imaging and puncture. The puncture site and path were chosen in the mid axillary line, and then an 18-gauge puncture needle was advanced into the appropriate calyx using a needle-guiding system fixed to the US probe.

A US-guided puncture through the cup of the desired calyx was established. A 0.38, floppy-tip guide wire was advanced into the chosen calyx. Tract dilatation was performed after opacification of the PCS, with a contrast medium in a retrograde fashion, under fluoroscopic guidance using Alken dilators up to 27 Fr, except in 5 cases where hypermobile kidney balloon dilatation was used. A 30 Fr Amplatz sheath was used, and then a standard 26 Fr, rigid nephroscope was used for stone retrieval (Figure 2). A 26 Fr nephrostomy tube was fixed at the end of the procedure.

Patient demographics, body mass index (BMI), stone case of residual stones with prolonged leakage there was a characteristics, operative time, intra- and postoperative 6 mm stone that passed spontaneously after 5 days without complications, stone clearance, and the total number of sessions intervention. the mean hospital stay was 3.2 days (range 2 to of the PCNL required were collected, tabulated, and analyzed 5 days). using the Statistical Package of Social Science (SPSS), version 11, software. Suitable statistical techniques were computed Postoperative complications in the form of fever occured in (frequencies, mean, standard deviation, and range). 4 cases (8.5%) and urinary leakage in 3 cases (6.4%). There

Results were insignificant differences (p = 0.018) between pre- and postoperative hemoglobin (11.3 ± 0.95, 10.8 ±1.3, respectively), as well as pre- and postoperative hematocrite value (32.7 ± 1.9, Patient demographics and stone features were summarized in 31.2 ± 3.25, respectively; p = 0.003). Tables 1 and 2. Intraoperative data of the study group were demonstrated in Table 3. Multiple punctures were done in 7 Discussion cases: lower and middle calices in 5 cases, lower and upper calices in 2 cases. The prone position has been the most commonly used position for PCNL, because this was the way the technique was invented; Intraoperative complications, including dilatation difficulties, however, the main reason for perseverance with this position were found in 5 cases (10.6%), and bleeding requiring must be the apprehension of colonic and vascular injury [9]. transfusion was found in 2 cases (4.2%). Visceral injury did not Various modifications in patient positioning for PCNL emerged occur in any of the studied cases. as urologists understood more of the surface anatomy of the kidney and related viscera. When patients were placed The stone-free rate was achieved in 44 cases (93.6%). Residual in the supine position for percutaneous nephrolithotomy, stones more than 4 mm were detected in 3 cases (6.4%). Stone the ipsilateral flank was elevated with a 1L or 3L water bag, free was considered if there were no residual stones or stones depending on a patient’s body mass [9]. Falahatkar and less than 4 mm. Subsequent auxiliary procedures were used colleagues [8] performed complete supine PCNL without a as DJ insertion and ESWL in 2 cases (4.2%), while in the third rolled towel under the flank and no change in leg position. We

UroToday International Journal original study UIJ Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access Table1. Patient demographic data. Table 2. Stone characteristics. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.07t1 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.07t2

Data Number Percent Data Number Percent Total number of cases 47 Stone site Age (mean + SD) 46.12 + 10.75 Pelvic stone 20 42.5 BMI in kg/sqm (mean + SD) 23.6 + 5.92 (8% were Calyceal stone (total) 18 38.3 morbid) Upper calyceal 2 4.2 Gender Middle calyceal 5 10.6 Male 30 63.8 Lower calyceal 11 23.4 Female 17 36.2 Staghorn 3 6.4 Comorbidity Upper ureteric stone 1 2.1 DM 4 8.5 Multiple stones* 5 10.6 COPD 6 12.7 Stone side Hypertension 6 12.7 Right 25 53.2 IHD 3 6.4 Left 22 46.8 Liver disease 1 2.1 Stone size mean (+ SD cm) 2.9 + 1.029 Multiple comorbidities* 4 8.5 Stone radiopacity Previous renal stone surgery 6 12.7 Opaque 42 89.4 (total) Lucent 5 10.6 Open 4 8.5 *Regarding multiple stones, 2 cases had stones in upper and PCNL 2 4.2 lower calices, while the other 3 cases had stones in the middle *Multiple comorbidities in 4 cases (2 cases had DM and and lower calices. hypertension; 1 case had COPD and IHD; 1 case had liver cirrhosis, DM).

In this study, the mean operative time was 70 minutes (range 60 to 120 minutes). The mean operative time in studies by Manohar considered that there was no essential difference in the basic et al. [2], Valdivia et al. [4], and Rana et al. [9] was 85, 74, and 65 principles and surgical techniques between 2 supine positions. minutes, respectively, which are comparable to this study. De Sio et al. [11] reported a much shorter mean operative time (43 The mean age in this study was 46.12 ± 10.75 (range 24 to 65 minutes), while others reported a much longer mean operative years). A patient’s number was 47, which was comparable to time, such as Zhou et al. [6] , Neto et al. [13], and Basiri et al. studies done by Shoma et al. [10], Ng et al. [3], Manohar et al. [14], who reported 162 ,120, and 111 minutes, respectively. [2], and De Sio et al. [11], who studied 53, 62, 62, and 39 cases, respectively. Larger studies were done by Valdivia et al. [4], Intraoperative Complications Steele and Marshall [1], and Rana et al. [9], who studied 520, 322, and 184 cases, respectively. In the current study, intraoperative complications included dilatation difficulties (10.6%), which were due to anteromedial In this study, the mean BMI in kg/sqm (± SD) was 23.6 ± 5.92 displacement of the kidney during dilatation of the tract when (4 patients, 8% were morbidly obese), which is comparable to a the dilators met the resistance of the renal capsule. The tract study done by Manohar et al. [2], who did supine PCNL in obese became longer and more perpendicular rather than parallel to patients, and the mean BMI was 24. While Hoznek et al. reported the fluoroscopy table. This issue was solved by extra abdominal 26.1 ± 5 [12]. Others used body weight instead of BMI [1,4,9,10]. compression during dilatation to minimize renal movement, the use of super-stiff guide wire, and 1-step ballon dilatation.

UroToday International Journal original study UIJ Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access Table 3. Intraoperative data. to cold fomentation and antipyretic drugs, while De Sio et al. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.07t3 [11] reported 1 case suffering from fever > 38.8 for 2 days, and their PUT showed a steinstrasse in the distal part of the ureter, Data Number Percent managed by a DJ stent. Hoznek et al. [12] reported that 1 case, Calyx Puncture out of 47 patients, had a fever. Upper calyceal 2 4.2 In our study, urinary leakage occurred in 3 cases after the Middle calyceal 6 12.7 removal of the nephrostomy tube (after 48 hours). One case Lower calyceal 32 68.1 was managed conservatively, while DJ stents were inserted 1 Multiple punctures 7 15 week postoperatively in the other 2 cases. Steele and Marshall [1] reported urine leaks in 3 out of 322 patients, who then Track dilation underwent supine PCNL. De Sio et al. [11] reported a prolonged Alken 42 89.4 leak from the percutaneous access in 4 out of 39 patients, Balloon 5 10.6 managed by stenting. Hoznek et al. [12] reported 2 cases of Stone disintigration urinary fistulas out of 47 patients.

Lithoclast 31 66 In this study, the mean hospital stay was 3.2 days (76.8 hours). In toto extraction 16 34 Hoznek et al [12] reported 3.4 ± 1.9 days, while Ng et al. [3] Nephrostomy drainage 47 100 reported a mean hospital stay of 209 hours in supine PCNL cases. Steele and Marshall [1] reported the range of hospital Mean operative time (mins) 47 100 stay as 72 to 144 hours, De Sio et al. [11] reported the mean hospital stay as 103 hours, and Neto et al. [13] reported the mean hospital stay as 129.6 hours.

Ultrasound before performing PCNL helps to plan the procedure Dilatation difficulties were reported by others (11 to 12%) and access site. The depth of the target and angulations of [9,10]. the needle and access can be planned, keeping in mind the avascular Brodel’s line. Usually, the posterior calyx is selected Bleeding requiring transfusion occurred in 2 cases (4.2%), which and the ultrasound can provide radiation-free, real-time was directly related to stone size, procedure duration, and the imaging guidance for the needle puncture [7]. Basiri et al. [15] creation of multiple tracts. One of them had a 2 cm stone in compared fluoroscopy and ultrasonography in a clinical trial and the middle anterior calyx and underwent direct puncture on concluded that access for PCNL using ultrasound guidance is an the stone (single stage, 1 tract). Another, with a 4 cm staghorn acceptable alternative to fluoroscopy. They found less radiation stone calculus without hydronephrosis, underwent lower and exposure with ultrasonography, and success and complication middle-caliceal puncture (single stage, 2 tracts) for complete rates comparable with those of fluoroscopy. Hosseini et al. [16] stone clearance. Both of these patients were diabetic and started prone PCNL with ultrasound guidance in 39 cases. They hypertensive. This was comparable with other series (3.2 to showed that ultrasound-guided PCNL can be a feasible, reliable, 5.2%) [1-3,8,14]. Fewer incidences were reported in some safe, and effective alternative to fluoroscopy in experienced cases (0 to 1.4%) [4,11], while a higher incidence was reported hands. in others (9.4 to 11%) [6,10], and this was attributed to their learning curve. Visceral injury did not occur in any of the Falahatkar and Allahkhah [17] noticed ultrasound-guided, studied cases. complete supine PCNL without fluoroscopy has some disadvantages. One problem is the use of lubricant gel on the Stone clearance rate in this study was 93.6%, which is sonography probe at the time of dilatation. A second problem comparable to other studies (70.5 to 95%) [2,3,9-11,13,14]. is that urologists are unfamiliar with sonographic images of Residual stones more than 4 mm occurred in 3 cases (6.4%). the kidney. Because the Amplatz dilatator and Amplatz sheath echo do not have good imaging quality, the experience of the Postoperative Complications surgeon plays a large role in finding the best access. Recently, Hoznek et al. [12] proceeded to puncture the kidney under In this study, fever did not exceed 38.5 and responded well combined ultrasound and fluoroscopic control, as in our study.

UroToday International Journal original study UIJ Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access 3. Ng MT, Sun WH, Cheng CW, Chan ES. Supine position is Published studies from different centers have shown that safe and effective for percutaneous nephrolithotomy. J supine PCNL is safe, and it has several benefits for the patient Endourol. 2004;18(5):469-474. PubMed ; CrossRef and several technical advantages for the surgeon [9-11,18]. Patient positioning is less demanding and time-consuming 4. Valdivia Uria JG, Valle Gerhold J, López López JA, because a change is not required from the lithotomy to the et al. Technique and complications of percutaneous prone position during the procedure [19]. nephroscopy: Experience with 557 patients in the supine position. J Urol.1998;160(6 pt 1):1975-1978. PubMed ; The supine position also allows greater versatility during stone CrossRef management since ureteroscopy can be performed if there are contralateral ureteral stones, or simultaneous procedures for 5. Hopper KD, Sherman JL, Luethke JM, Ghaed N. The renal, ureteral, and bladder stones in the same single supine retrorenal colon in the supine and prone patient. lithotomy position. A final advantage of the supine PCNL Radiology.1987;162(2):443-446. PubMed position is that urologists are more comfortable adopting a sitting posture during stone management. Although supine 6. Zhou X, Gao X, Wen J, Xiao C. Clinical value of minimally percutaneous nephrolithotomy is routine in some surgical Invasive percutaneous nephrolithotomy in the supine centers throughout the world, its popularity in the field position under the guidance of real-time ultrasound: of urology, due to a deficiency in its training in educational report of 92 cases. Urol Res. 2008;36(2):111-114. PubMed ; centers, as a whole, is still minimal [20]. CrossRef

Lastly, systematic literature review was performed by Wu and 7. Kang PS, Paspulati RM. Ultrasound-Guided Genitourinary his colleagues [21] who concluded, for general patients with Interventions. Ultrasound Clin. 2007;2(1):115-120. CrossRef kidney calculi, PCNL in the supine position has similar, stone- free rates compared with the prone position. Supine PCNL 8. Falahatkar S, Neiroomand H, Enshaei A, Kazemzadeh does not increase related complications. The operative times M, Allahkhah A, Jalili MF. Totally ultrasound versus significantly decrease in the supine position. However, there is fluoroscopically guided complete supine percutaneous still no consensus on the optimal position for PCNL. nephrolithotripsy: a first report. J Endourol. 2010;24(9):1421-1426. PubMed ; CrossRef Conclusion 9. Rana AM, Bhojwani JP, Junejo NN, Das Bhagia S. Tubeless PCNL in the supine position, under ultrasound-guided puncture, PCNL with patients in supine position: procedure for is feasible, safe, and successful, with minimal complications. all seasons? with comprehensive technique. Urology. 2008;71(4):581-585. PubMed ; CrossRef Acknowledgements 10. Shoma AM, Eraky I, El-Kenawy MR, El-Kappany HA. Percutaneous nephrolithotomy in the supine position: The authors are grateful to the residents in the urology technical aspects and functional outcome compared department of Benha University Hospital, Benha, Egypt, for with the prone technique. Urology. 2002;60(3):388-392. help in patient recruitment and follow-up. PubMed ; CrossRef References 11. De Sio M, Autorino R, Quarto G, et al. Modified supine versus prone position in percutaneous nephrolithotomy for 1. Steele D, Marshall V. Percutaneous nephrolithotomy in renal stones treatable with a single percutaneous access: the supine position: A neglected approach? J Endourol. a prospective randomized trial. Eur Urol. 2008;54(1):196- 2007;21(12):1433-1437. PubMed ; CrossRef 202. PubMed ; CrossRef 2. Manohar T, Jain P, Desai M. Supine percutaneous 12. Hoznek A, Rode J, Ouzaid I, et al. Modified Supine nephrolithotomy: Effective approach to high-risk and Percutaneous Nephrolithotomy for Large Kidney and morbidly obese patients. J Endourol. 2007;21(1):44-49. Ureteral Stones: Technique and Results. Eur Urol. PubMed ; CrossRef 2012;61(1):164-170. PubMed ; CrossRef

UroToday International Journal original study UIJ Percutaneous Nephrolithotomy in the Supine Position with Ultrasound-Guided Renal Access 13. Neto EA, Mitre AI, Gomes CM, Arap MA, Srougi M. Percutaneous nephrolithotripsy with the patient in a modified supine position. J Urol. 2007;178(1):165-168. PubMed ; CrossRef

14. Basiri A, Sichani MM, Hosseini SR, et al. X-ray-free percutaneous nephrolithotomy in supine position with ultrasound guidance. World J Urol. 2010;28(2):239-244. PubMed ; CrossRef

15. Basiri A, Ziaee AM, Kianan HR, Mehrabi S, Karami H, Moghaddam SM. Ultrasonographic versus fluoroscopic access for percutaneous nephrolithotomy: a randomized clinical trial. J Endourol. 2008;22(2):281-284. PubMed ; CrossRef

16. Hosseini MM, Hassanpour A, Farzan R, Yousefi A, Afrasiabi MA. Ultrasonography-guided percutaneous nephrolithotomy. J Endourol. 2009;23(4):603-607. PubMed ; CrossRef

17. Falahatkar S, Allahkhah A. Recent Developments in Percutaneous Nephrolithotomy: Benefits of the Complete Supine Position. UroToday Int J. 2010;3(2):1944-5784. CrossRef

18. Domenech A, Vivaldi B, Diaz C, et al. Complications in percutaneous nephrolithotomy: A comparative study between the supine and prone positions using the modified clavien system. Urology. 2008;72(5 suppl 1):S16. CrossRef

19. de la Rosette JJ, Tsakiris P, Ferrandino MN, Elsakka AM, Rioja J, Preminger GM. Beyond prone position in percutaneous nephrolithotomy: a comprehensive review. Eur Urol. 2008;54(6):1262-1269. PubMed ; CrossRef

20. Falahatkar S, Farzan A, Allahkhah A. Is complete supine percutaneous nephrolithotripsy feasible in all patients? Urol Res. 2011;39(2):99-104. PubMed ; CrossRef

21. Wu P, Wang L, Wang K. Supine versus prone position in percutaneous nephrolithotomy for kidney calculi: a meta- analysis. Int Urol Nephrol. 2011;43(1):67-77. PubMed ; CrossRef

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.07 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 A Rare Cause of Acute Urinary Retention in a Young Female: Leiomyoma Bladder

Bikash Bawri,1 Rajeev T Puthenveetil,2 Saumar J Baruah,3 Sasanka K Barua,4 Puskal K Bagchi4 1Department of Urology, Gauhati Medical College Hospital, Guwahati, Assam, India 2Associate Professor, Department of Urology, Gauhati Medical College Hospital, Guwahati, Assam, India 3Professor and HOD, Department of Urology, Gauhati Medical College Hospital, Guwahati, Assam, India 4Assistant Professor, Department of Urology, Gauhati Medical College Hospital, Guwahati, Assam, India Submitted September 9, 2011 - Accepted for Publication November 9, 2011

ABSTRACT Leiomyoma represents the largest subgroup of benign mesenchymal tumors that may arise anywhere within the genitourinary tract. Usual presenting symptoms include voiding symptoms such as obstruction and irritation. It can be diagnosed by careful physical examination assisted with ultrasound and endoscopic evaluation, but the confirmatory diagnosis is always histological. Bladder-conservative surgery is usually contemplated asthe treatment of choice, be it transurethral resection or open surgery. This can include partial cystectomy due to the benign nature of the disease. Although the occurrence of this tumor is rare, it should be suspected with any urinary bladder tumor presenting with benign features. The prognosis is good with bladder preservative protocols.

Introduction [4]. Typically, it occurs in the fourth and fifth decades of life. The most common presenting complaints are urinary voiding Benign mesenchymal tumors make up 1 to 5% of all bladder symptoms, such as obstruction and irritation. Surgery is the neoplasms, with leiomyoma representing the largest subgroup of these benign tumors (.04 to .5%) [1,3]. A leiomyoma is standard treatment, and the surgical approach depends on a benign, smooth muscle tumor most often located in the tumor size and localization at the bladder wall. Prognosis is uterus or gastrointestinal tract. However, these tumors may good due to the benign behavior of these lesions. We describe arise anywhere within the genitourinary tract and are usually a case of urinary bladder leiomyoma in a young woman with asymptomatic unless urinary tract function is affected [2]. They acute urinary retention. Although not initially suspected, the are predominantly found in women, although men can also be affected. Approximately 250 cases have been reported to date, diagnosis of urinary bladder leiomyoma was subsequently, including patients who had leiomyoma in a urethral location histologically confirmed.

KEYWORDS: Leiomyoma; Genitourinary tract; Obstruction; Partial cystectomy CORRESPONDENCE: Bikash Bawri, MD, RK Singh Apartment, House No 54, Ashram Road, Kasturba Nagar, Ulubari, Guwahati-781007, Assam, India ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 83. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.01

UroToday International Journal case report UIJ A Rare Cause of Acute Urinary Retention in a Young Female: Leiomyoma Bladder CASE REPORT Figure 1. A CT scan showing bladder mass arising from the right, anterolateral aspect. A 27-year-old woman presented with acute urinary retention http://dx.doi.org/10.3834/uij.1944-5784.2012.02.01f1 and a 7-month history of urgency, urge incontinence, and intermittent hematuria associated with dull, intermittent, lower abdominal pain. The patient had similar episodes of acute retention during this period, which subsided after some movement by the patient, similar to the ball-valve effect. There was no history of weight loss or other constitutional symptoms. The physical examination was normal, except for anemia and a freely movable, solid mass in the suprapubic region, which was not tender. It was firm, smooth surfaced, and well defined. Urinalysis demonstrated significant red blood cells (RBCs), and all other laboratory investigations were normal, except for the anemia. The abdominopelvic ultrasound (US) demonstrated a solid mass of 80.5 mm by 65.5 mm inside the urinary bladder. Computerized tomography (CT) confirmed the solid mass as heterogeneously poor. It measured 61 by 80.7 by 92.3 mm, rising from the right anterolateral aspect of the bladder where there was bladder-wall thickening measuring up to 16.9 mm. The lesion was clear from the bilateral vesicoureteric junction (VUJ), and perivesical fat appeared clear with bilateral, mild hydroureteronephrosis and no lymphadenopathy [Figure 1]. Figure 2. Cystoscopic view showing normal bladder mucosa with submucosal mass. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.01f2 On cystoscopy, an anterolaterally located, intraluminally protruding solid mass covered by normal bladder mucosa was seen [Figure 2]. Both the ureteric orifices were normally located and free of the tumor. Upon suspicion of malignancy, the patient underwent pelvic exploration, which revealed an intramural, capsulated, solid mass arising from the anterolateral wall of the bladder. It was well capsulated, its margins were distinct, and it was protruding intravesically. The overlying mucosa was smooth, and both ureteric orifices were typically uninvolved. Partial cystectomy was done with a 2 cm bladder margin around the pedicle of the mass. The operative room time was 80 minutes, with an intraoperative blood loss of approximately 100 ml [Figure 3].

Pathological examination revealed a 95 by 90 by 55 mm multinodular, encapsulated mass with a light brown external surface. The cut surface was grey-white and whorled, with mucoid and hemorrhagic areas. Microsections showed interlacing fascicles of smooth-muscle bundles, with mild, cellular atypia and areas of myxoid change, suggestive of leiomyoma of the urinary bladder [Figure 4]. There was no

UroToday International Journal case report UIJ A Rare Cause of Acute Urinary Retention in a Young Female: Leiomyoma Bladder Figure 3. Intraoperative picture showing large submucosal Figure 4. Microsections showing interlacing fascicles of bladder mass with a pedicle. smooth muscle bundles. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.01f3 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.01f4

invasion of the bladder wall, and the margins were uninvolved disontogenic theory, which suggests its origin comes from by the tumor, with no evidence of malignancy. embryogenic rests of Müller and Wolffian ducts, 3) vascular- irritative theory, and 4) Lips-Chutz’s theory, which suggests its The patient had an uneventful recovery following the origin is secondary to an endocrine disorder, with estrogen and procedure. The patient remained well at a 1-year follow-up, progesterone having a primary role. This theory supports peak and no further urinary frequency and hematuria were noted. incidence in females when fertile, and the presence of steroidal ovarian receptors on the tumor [8]. DISCUSSION Macroscopically, these are round or oval tumors with an elastic consistency and irregular surface. The size varies, with reports Leiomyoma originates from smooth-muscle bundles, and of tumors as big as 30 cm, especially in extravesical localization connective tissue surrounds it. Therefore, it can arise in any [9,10]. In bladder lesions, the localization is submucosal in organ that contains this tissue. The most common localizations 63%, and at cystoscopy, we can see a sessile or pedunculated are the skin, womb, retroperitoneum, and genitourinary and lesion covered by normal mucosa. The subserosal localization gastrointestinal tracts [5,7,9]. In the genitourinary tract, it represents 11 to 30% of the cases, having a characteristic pedicle is most frequent in the kidney and bladder, especially at the that bounds it with the bladder. The intramural localization is trigone and bladder neck [7,9,10]. A review by Goluboff et al. of less frequent and represents 7 to 17% of the cases, with a well- 37 cases in the English literature showed that the mean patient encapsulated tumor in the bladder wall [3,6,9]. Leiomyomas can age was 44 years and that 76% of patients were women [6]. remain asymptomatic for many years, reaching considerable size, unless they affect the normal function of the lower urinary The genesis of this lesion remains a mystery; however, there are tract [9]. Endoluminal tumors are symptomatic, presenting multiple theories that try to explain this question [7]: 1) Blum’s with urinary tract infections, hematuria, irritative symptoms irritative-inﬂammatory theory, which suggests the presence of (especially at the bladder neck), or obstructive symptoms, chronic inﬂammatory stimuli over the smooth muscle, 2) Piegel’s causing even acute bladder outlet obstruction secondary to a

UroToday International Journal case report UIJ A Rare Cause of Acute Urinary Retention in a Young Female: Leiomyoma Bladder valve effect [5,6,9,10], as in our case. Intramural and subserosal 30% were removed by transurethral resection [6]. Prognosis tumors are, in general, asymptomatic and the diagnosis is is good and recurrence is rare if the resection is adequate; incidental. At cystoscopy, submucosal tumors appear as a therefore, it seems unnecessary to establish follow-up protocols. sessile or pedunculated lesion covered by normal mucosa, but However, Lake, in 1981, described what is, to date, the only it could be normal if the tumor is intramural or subserosal. case of a leiomyoma with malignant degeneration [7]. The The same situation can occur in the intravenous pyelography laparoscopic approach is an excellent option for tumors located (IVP), showing a filling defect in the bladder wall if the lesion at the mobile wall of the bladder, allowing an easy and safe is submucosal. Ultrasound allows us to define the solid or cystic procedure. Bladder-wall edges are simple to identify, especially nature of the lesion, showing, in these cases, a solid, smooth if simultaneous cystoscopic control is used, which adds the wall lesion with homogeneous echoes. Transvaginal ultrasound option of resecting the tumor with the resectoscope [11]. is an excellent option in female posterior bladder-wall tumors in subserosal localization [6,9]. Computed tomography gives us Leiomyoma of the urinary bladder is actually not an uncommon information about the size, position, and relationship between disease for middle-aged women presenting with obstructive the tumor and bladder wall. An MRI shows a leiomyoma with and irritative voiding symptoms. Careful physical examination an intermediate signal on T1 weighted images, with contrast and ultrasound may occasionally discover it. It is readily and between the tumor and the urine, which has a low-signal successfully treated with TUR or open surgery, in most cases. intensity. Nevertheless, imaging tests add important data that It should be considered for its successfully diagnosable and suggest the benign nature of these tumors, like the presence treatable nature in any pelvic mass involving the bladder wall. of a well-circumscribed lesion with homogeneous density, poor Although only 250 cases have been reported to date, our case enhancement with contrast media, and normal, perivesical fat. presented at a very young age, with typical symptoms of ball- There is no test that allows us to differentiate a leiomyoma from valve-type acute retention with a large-sized leiomyoma. leiomyosarcoma; therefore, pathologic diagnosis is mandatory [5]. Leiomyomas are firm and rubbery in consistency, appear as References whitish-gray, round to ovoid nodules with a spiral appearance of smooth-muscle fibers, and eosinophilic cytoplasm with less than 2 mitotic figures per high-power field. They are surrounded by 1. Campbell EW, Gislason GJ, et al. Benign mesothelial a variable amount of connective tissue, and there is no necrosis tumors of the urinary bladder: Review of literature and a or cellular atypia [6]. report of a case of leiomyoma. J Urol. 1953;70(5):733-741. PubMed In a literature review by Silva-Ramos et al., 90 bladder 2. Knoll LD, Sergura JW, Scheithauer BW. Leiomyoma of the leiomyomas where analyzed, 28 of which where biopsied bladder. J Urol. 1986;136(4):906-908. PubMed before the definitive treatment. All samples obtained with a Tru-Cut needle and transurethral resection (TUR) were 3. Ojea Calvo A, Núñez López A, Alonso Rodrigo A, et al. diagnostic, whereas the cold-cup biopsy samples showed a [Bladder leiomyoma]. Actas Urol Esp. 2001;25(10):759-763. 50% false negative. Fine-needle aspiration biopsy was the least PubMed useful diagnostic tool [5]. 4. Cornella JL, Larson TR, Lee RA, Magrina JF, Kammerer-Doak The treatment depends on the tumor size, localization, and D. Leiomyoma of the female urethra and bladder: report of twenty-three patients and review of the literature. relationship with the bladder wall [6]. Surgery is indicated Am J Obstet Gynecol. 1997;176(6):1278-1285. PubMed ; because of the potential growing capacity of these tumors [9]. CrossRef Given the benign nature of these lesions, the surgery must be as conservative as possible. Submucosal tumors can be managed 5. Silva-Ramos M, Massó P, Versos R, et al. [Leiomyoma of the by transurethral resection, noting the size is an important issue. bladder. Analysis of a collection of 90 cases]. Actas Urol Subserosal and huge submucosal lesions can be managed by Esp. 2003;27(8):581-586. PubMed ; CrossRef enucleation or with partial cystectomy. In Goluboff’s review of the literature, 62% were treated by open resection, whereas

UroToday International Journal case report UIJ A Rare Cause of Acute Urinary Retention in a Young Female: Leiomyoma Bladder 6. Goluboff E, O´Toole K, Sawczuk IS. Leiomyoma of bladder: Report of case and review of literature. Urology. 1994;43(2):238-241. PubMed ; CrossRef

7. Rubio Muñoz A, Bono Ariño A, Berné Manero JM, et al. [Leiomyoma of the bladder]. Arch Esp Urol. 2000;53(10):934-937. PubMed

8. Furuhashi M, Suganuma N. Recurrent bladder leiomyoma with ovarian steroid hormone receptors. J Urol. 2002;167(3):1399-1400. PubMed ; CrossRef

9. Jiménez Aristu JI, Lozano Uruñuela F, de Pablo Cárdenas A, et al. [Leiomyoma of the bladder. Report of a case]. Actas Urol Esp. 2001;25(3):223-225. PubMed ;

10. Belis JA, Post GJ, Rochman SC, Milam DF. Genitourinary leiomyomas. Urology. 1979;13(4):424-429. PubMed ; CrossRef

11. Jeschke K, Wakonig J, Winzely M, Henning K. Laparoscopic partial cystectomy for leiomyoma of the bladder wall. J Urol. 2002;168(5):2115-2116. PubMed ; CrossRef

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.01 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012

Inflammatory Pseudotumor of the Urachus

Raj Kumar Sharma, Vir Kumar Jain, S Mukherjee, SN Mondal, D Karmakar Calcutta National Medical College, Kolkata, India Submitted November 5, 2011 - Accepted for Publication December 9, 2011

ABSTRACT

Urachal diseases often create serious diagnostic dilemmas owing to their uncommon occurrences and the diversity of their presentations. We present a rare case of inflammatory pseudotumor of the urachus. The rarity and confusing nature of this condition prompted us to submit the present information.

Introduction prompted us to submit the present information.

Urachal diseases often create serious diagnostic dilemmas CASE REPORT owing to their uncommon occurrences and the diversity of their presentations. This is especially true for its tumors. Malignant A male child of 12 years of age presented at our surgical tumors are common among all the tumors of the urachus, of department with complaints of a lump in the lower abdomen which adenocarcinoma is the most common. Benign tumors, for 2 months, and pain over the lower abdomen for the previous however, are uncommon in this vestigial organ [1]. Inflammatory 3 days. There was no history of vomiting, alteration of bowel pseudotumor is a benign, fibromuscular tumorous growth habit, or urinary symptoms. On abdominal examination, a in which there is proliferation of plasma cells, lymphocytes, single intra-abdominal lump of approximately 10 cm by 8 cm in and histiocytes in a benign-looking, spindle-shaped stroma size was found occupying the mainly hypogastric and umbilical (myofibroblasts). It is commonly seen in abdominal and pelvic regions, along with adjacent areas of iliac fossae, which did structures. Its occurrence in the urachus has been reported only not move with respiration. Palpation revealed a non-tender a couple of times in the literature. We present a rare case of mass, which was of normal temperature and firm-to-hard in inflammatory pseudotumor of the urachus, which was also consistency. It had a bosselated surface and ill-defined margins unique for the diagnostic dilemmas it created for the treating in its lower part. Percussion revealed dullness over the lump. team. The rarity and confusing nature of this condition The liver was not enlarged, the spleen was not palpable, and

KEYWORDS: Inflammatory pseudotumor; Urachus CORRESPONDENCE: Raj Kumar Sharma, MBBS, MS, MCh, Department of Urology, Calcutta National Medical College, Kolkata, West Bengal, India 700046 ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 94. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.12

UroToday International Journal case report UIJ Inflammatory Pseudotumor of the Urachus there was no other apparent abnormal finding. Figure 1. Inflammatory pseudotumor on right hand and urinary bladder with Foley catheter bulb on left hand. On routine investigation, total and differential white blood- http://dx.doi.org/10.3834/uij.1944-5784.2012.02.12f1 cell counts were normal, as was the routine examination of urine. Fine-needle aspiration was done and the cytology report was inconclusive. Ultrasound examination revealed a solid, multinodular mass of 63 mm by 71 mm by 63 mm in the right iliac fossa, extending up to the umbilicus. On CT scan, a large, solid, lobulated mass of 11 cm by 6 cm was seen in the pelvis (more towards the right side), which was slightly hypodense in attenuation. The mass was seen displacing bowels and indenting the bladder. It was continuous with anterior abdominal wall muscle. On IV contrast administration, the mass showed heterogeneous enhancement with sparing of the central region (dense fibrosis).

Based on these findings, an exploratory laparotomy was performed. The laparotomy revealed a large lobulated mass, which was free from adjacent bowel loops and mesenteries. Its lower part was attached to a dome of the urinary bladder in a pedunculated form (Figure 1). It was excised after securing hemostasis and was sent for histopathological examination. Postoperative recovery was uneventful.

Histopathological examination of the specimen grossly revealed Inflammatory pseudotumor of the urachus is one such tumor, a greyish-white, soft-to-firm mass. On microscopic examination, which runs a benign clinical course. The most common site for the section revealed a spindle-cell tumor composed of loose this pseudotumor is the lung and mediastinum, followed by fibromyxoid stroma with spindle-and-stellate-shaped cells mixed extrapulmonary sites, the list of which includes almost every with dense lymphoplasmacytic and mononuclear infiltrate. organ in the body [5,6]. Although the spindle cells showed mild pleomorphism, there was no mitotic activity. A focus of ischemic necrosis was also Despite its common predilection for abdominal and pelvic seen. The final pathological diagnosis came out to be a spindle organs, including the urinary bladder, bowel, liver, and cell tumor suggestive of inflammatory pseudotumor. peritoneum [6,7], it has been rarely reported in the urachal remnant [8,9]. Along with the rarity of this tumor, our case DISCUSSION is a good example of the diagnostic confusion the lumps of the urachus can create for a clinician. It resisted complete The urachus is a vestigial remnant of 2 embryonic structures, diagnosis until imaging investigations, exploratory laparotomy, which are urogenital sinus (the precursor of urinary bladder) and and histopathology were correlated. Thus, the importance allantois (the derivative of yolk sack). Normally, it is obliterated of investigations in urachal lumps is again underscored here, before birth, leaving a fibrous band extending from the dome which was stressed previously [4,5]. of the urinary bladder to the umbilicus. Common pathologies of this structure are congenital anomalies and infections [2]. Finally, regarding the treatment of inflammatory pseudotumor, Tumors are rare findings in the urachus. The majority of tumors 2 schools of thought are advocated. Our treatment of in the urachus are malignant (0.5% of all bladder carcinomas), simple excision was due to the history, clinically as well as adenocarcinomas constituting the majority of this group (80%) preoperatively, which was more in favor of a benign tumor. [1]. Benign tumors of the urachus are extremely uncommon. Simple excision has been used previously in similar cases This group consists of adenomas, fibromas, fibroadenomas, [10]. A second school of thought also advocates that in cases fibromyomas, and hamartomas [2]. These benign tumors must where preoperative findings are inconclusive or in favor of be thoroughly evaluated owing to the potential confusion they malignancy, aggressive surgery should be the choice [9]. The best intervention frequently depends on the discretion of the create in the diagnosis of abdominal lumps as a whole [3,4,9].

UroToday International Journal case report UIJ Inflammatory Pseudotumor of the Urachus individual surgeon; however, aggressive surgery is preferred over simple excision if there is any doubt about the presence of malignancy.

References

1. Sheldon CA, Clayman RV, Gonzalez R, et al. Malignant urachal lesions. J Urol. 1984;131(1):1-8. PubMed

2. Yu JS, Kim KW, Lee HJ, et al. Urachal Remnant Diseases: Spectrum of CT and US Findings. Radiographics. 2001;21(2):451-461. PubMed

3. Eble JN, Hull MT, Rowland RG, Hostetter M. Villous adenoma of the urachus with mucusuria: a light and electron microscopic study. J Urol. 1986;135(6):1240-1244. PubMed

4. Narumi Y, Sato T, Kuniyama K, et al. Vesical Dome Tumors: Significance of Extravesical Extension on CT. Radiology. 1988;169(2):383-385. PubMed

5. Narla LD, Newman B, Spottswood SS, Narla S, Kolli R. Inflammatory Pseudotumor.Radiographics . 2003;23(3):719- 729. PubMed ; CrossRef

6. Coffin CM, Humphrey PA, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey. Semin Diagn Pathol. 1998;15(2):85- 101. PubMed

7. Bonnet JP, Basset T, Dijoux D. Abdominal inflammatory myofibroblastic tumors in children: report of an appendiceal case and review of the literature. J Pediatr Surg. 1996;31(9): 1311-1314. PubMed ; CrossRef

8. Nascimento AF, Dal Cin P, Cilento BG, et al. Urachal inflammatory myofibroblastic tumor with ALK gene rearrangement: a study of urachal remnants. Urology. 2004;64(1):140-144. PubMed ; CrossRef

9. Tunca F, Sanli O, Demirkol K, et al. Inflammatory pseudotumor of urachus mimicking invasive carcinoma of bladder. Urology. 2006;67(3):623.e1-623.e3. PubMed

10. Lee HJ, Kim JS, Choi YS, et al. Treatment of Inflammatory Myofibroblastic Tumor of the Chest: The Extent of Resection. Ann Thorac Surg. 2007;84(1):221-224. PubMed ; CrossRef

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.12 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Lymphoepithelioma-like Carcinoma of the Bladder: Is the Prognosis Different from Conventional Bladder Carcinoma?

Eng Hong Goh,1 Akhavan Adel,1 Praveen Singam,1 Christopher Chee Kong Ho,1 Guan Hee Tan,1 Badrulhisham Bahadzor,1 Zulkifli Md Zainuddin,1 Isa Mohamed Rose2 1Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre 2Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre Submitted June 12, 2011 - Accepted for Publication August 12, 2011

ABSTRACT Recognition of other histological variants of urothelial carcinoma of the bladder is important because they may mimic benign lesions or have different clinical implications and associated prognoses, as well as treatment protocols. We report a case of lymphoepithelioma-like carcinoma (LELCA) in the bladder and discuss this rare entity with a review of other articles. Although we could not draw a conclusion on this particular disease, it is hoped that by adding cases with sufficient detail into literature, we will enable a more thorough and meaningful study where characteristics of the disease and the appropriate treatment regime could be facilitated.

Introduction case has given us an opportunity to review the various papers and make a discussion on this interesting disease.

Lymphoepithelioma is a form of undifferentiated carcinoma that was identified primarily in the nasopharynx in Asian Case report patients. In this location, it is in close pathogenetic relation to Epstein-Barr virus (EBV), although such an association has A 71-year-old Chinese woman had repeatedly presented with a not been documented for lymphoepithelioma-like carcinoma history of suprapubic pain, dysuria, and intermittent hematuria (LELCA) of the urinary bladder. In addition to the bladder, for the last 7 years. All of these episodes were treated as LELCA has been documented in other organs, including urinary tract infections by her general practitioner. However, salivary glands, the thymus, lungs, skin, the stomach, the after a severe bout at the end of 2009, she developed a fever, uterine cervix, and breasts [1]. First reported by Zuckerberg chills, and rigors, in addition to the usual urinary symptoms et al. in 1991 [2], LELCA of the urinary bladder has gradually aforementioned. She was admitted to a private hospital in gained recognition worldwide, but it seems that there is still another district, and it was during this admission that she was no unanimous agreement on its subtypes or its prognosis. Our found to have a growth at the posterior wall of her bladder.

KEYWORDS: Bladder; Lymphoepithelioma-like carcinoma; Cancer CORRESPONDENCE: Eng Hong Goh, Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur, 56000, Malaysia ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 84. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.02

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.02 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ®

UroToday International Journal case report UI Lymphoepithelioma-like Carcinoma of the Bladder: Is the Prognosis Different from Conventional Bladder J Carcinoma? Figure 1. CT scan of the abdomen showing a tumor at diffusely infiltrating and rather undifferentiated malignant the right posterolateral aspect of the bladder infiltrating cells arranged in sheets, and trabeculae with pleomorphic nuclei posteriorly as well as onto the right vesicoureteric and prominent nucleoli. There was also a prominent lymphoid junction. A DJ stent positioned in the right ureter is seen infiltrate associated with the tumor sheets and clumps. The in the bladder. malignant cells infiltrated into the underlying muscularis http://dx.doi.org/10.3834/uij.1944-5784.2012.02.02f1 propria up to the perivesical soft tissue and into the posterior cervical region. Fortunately, the surgical margin was clear, and there was no evidence of lymphovascular invasion. However, a 1 cm, right obturator node, out of 27 lymph nodes, harbored the malignant cells similar to those seen in the bladder. The malignant tissues stained positively for cytokeratin, CD3, CD20, p53, and Ki67 (90% high), but negatively for CK20 (Figures 2 and 3). A diagnosis of pure lymphoepithelioma-like carcinoma of the bladder was thus made. During her follow-up 14 months later, she was not given adjuvant therapy and was free of the disease, both clinically and radiologically.

Discussion

There have been numerous studies on this particular disease. Given that it is an uncommon entity with an incidence of 0.4 to 1.3% of all bladder carcinomas [2], most studies are either case reports or a case series with a small number of patients. The largest study to date was performed by Williamson et al. who described 34 cases in the bladder in 2011 [3]. Other large case series included those by Tamas et al. [4] with 28 cases in 2007, Lopez-Beltran et al. [5], which reported 13 cases in 2000, Holmang et al. [6] with 9 cases in 1998, and Amin et al. with 11 cases in 1994 [1]. A report by Serrano et al. in 2008 compiled all cases of LELCA of the bladder by searching through PubMed in English literature. It produced very informative details and characteristics of the disease in the form of tables [7]. We The initial transurethral resection of the bladder tumor (TURBT) actually attempted to compile all of these cases for the purpose revealed a histopathology finding of muscle-invasive, high- of analysis, as well as comparison, with the large series of grade urothelial carcinoma, but the specimen was unavailable conventional, transitional-cell carcinoma, but the effort was for another inspection at our institution due to logistics and hindered by inconsistency in classification and a lack of vital costs. Her subsequent management at our hospital included details. a work-up computed tomography (CT) scan (Figure 1) and bone scans showing T4aN2M0 disease, with bladder growth It is unfortunate that we could not compare the 2 infiltrating to the vagina and right vesicoureteric orifice. histological specimens of our patient, nor could we explain This resulted in right obstructive uropathy and regional the differences, although there is a propensity of urothelial lymphadenopathies. The patient refused any neoadjuvant carcinoma for divergent variation and abundant variability therapy. She underwent an uneventful cystectomy, including in tumor morphology [3]. The histological pattern and the removal of her anterior portion of the vagina, uterus, both subclassification of LELCA of the bladder have been well fallopian tubes, and ovaries, as well as a lymphadenectomy described in many earlier papers [1,4,6]. Its importance lies to iliac level and ileal conduit creation in March 2010. The in the fact that the prognosis of “pure” or “predominant” intraoperative frozen-section assessment at the ureteric margin disease is considered better than the conventional carcinoma needed repeating, as there was tremendous difficulty in of the bladder, whereas the prognosis of the “focal” disease identifying the malignant cellular margin in the first samples. does not differ from the conventional type [1,2,5]. However, The official histopathology result reported the presence of Tamas et al., who subclassified their cases into either “pure” or

UroToday International Journal case report UI Lymphoepithelioma-like Carcinoma of the Bladder: Is the Prognosis Different from Conventional Bladder J Carcinoma? Figure 2. Clump of large, poorly differentiated malignant Figure 3. Immunostain showing positively stained cells surrounded by an infiltrate of lymphocytes and malignant cells surrounded by infiltrate of unstained occasional eosinophils (H and E x 200). lymphocytes (cytokeratin x 200). http://dx.doi.org/10.3834/uij.1944-5784.2012.02.02f2 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.02f3

“mixed” types, did not share their findings. They observed that bladder with adequate and comparable details in literature, a the outcomes similarly disregarded subclassification. The paper more precise understanding of this disease and a comparison also claimed that LELCA, as a whole, shared similar outcomes with the conventional urothelial carcinoma can be facilitated. with conventional urothelial carcinoma [4]. In regards to the Venturing out of the avenue of morphological patterns may differing opinions, many of these papers reported that the T open up new insights into this particular disease. stage of the disease and the N status—crucial prognostic factors— were tremendously unknown. The latest and largest series by References Williamson et al. included the N status in almost all of their cases and reported a favorable prognosis in “pure” or “predominant” 1. Amin MB, Ro JY, Lee KM, et al. Lymphoepithelioma- cases, but the number of patients involved was quite small; i.e., only 5 [3]. Determining the prognosis is vital, as the arguments have like carcinoma of the urinary bladder. Am J Surg Pathol. primarily concentrated on whether or not bladder preservation 1994;18:466-473. PubMed ; CrossRef therapy is appropriate [3,4]. Taking into account our patient, with a 7-year history of symptoms, a final stage of T4aN1M0, and the 2. Porcaro AB, Gilioli E, Migliorini F, Antoniolli SZ, Lannucci absence of neoadjuvant or adjuvant therapy while remaining A, Comunale L. Primary lymphoepithelioma like disease-free until the present moment, the notion that “pure” or carcinoma of the urinary bladder: Report of one case “predominant” LELCA has a favorable prognosis is perhaps true. with review and update of the literature after a pooled Is there another prognosis determinant in LELCA of the bladder? analysis of 43 patients. Int Urol Nephrol. 2003;35:99- Thus far, attention has been paid to the morphological pattern of 106. PubMed ; CrossRef the tumor, but the molecular abnormalities have not been studied thoroughly yet [3]. 3. Williamson SR, Zhang S, Lopez-Beltran A, et al. Lymphoepithelioma-like carcinoma of the urinary In conclusion, it is our opinion that “pure” or “predominant” LELCA carries a positive outcome based on our experience, as bladder: Clinicopathologic, immunohistochemical, and well as that of others, although current limited data could not molecular features. Am J Surg Pathol. 2011;35:474-483. prove the evidence sufficiently. By pooling cases of LELCA of the PubMed ; CrossRef

UroToday International Journal case report UI Lymphoepithelioma-like Carcinoma of the Bladder: Is the Prognosis Different from Conventional Bladder J Carcinoma? 4. Tamas EF, Nielsen ME, Schoenberg MP, Epstein JI. Lympoepithelioma-like carcinoma of the urinary tract: A clinicopathological study of 30 pure and mixed cases. Mod Pathol. 2007;20:828-834. PubMed ; CrossRef

5. Lopez-Beltran A, Luque RJ, Vicioso L, et al. Lymphoepithelioma-like carcinoma of the urinary bladder: A clinicopathologic study of 13 cases. Virchows Arch. 2001;438:552-557. PubMed ; CrossRef

6. Holmäng S, Borghede G, Johansson SL. Bladder carcinoma with lymphoepithelioma-like differentiation: A report of 9 cases. J Urol. 1998;159(3):779-782. PubMed ; CrossRef

7. Serrano GB, Fúnez FA, López RG, et al. Bladder lymphoepithelioma-like carcinoma. Bibliographic review and case report. Arch Esp Urol. 2008;61(6):723-729. PubMed

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Mondor’s Disease of the Penis: A Forgotten Entity

Kapil Singla, Ashish Kumar Sharma, Sistla Bobby Viswaroop, Ganesh Gopalakrishnan, Sangam Vedanayagam Kandasami Department of Urology, Vedanayagam Hospital, Coimbatore, Tamil Nadu, India Submitted October 19, 2011 - Accepted for Publication November 23, 2011

ABSTRACT Introduction: Thrombophlebitis of the superficial dorsal vein of the penis, known as Mondor’s disease of the penis, was first described by Braun-Falco in 1955. Case Presentation: An apparently healthy 37-year-old man presented with painful swelling of the dorsal aspect of his penis. Doppler ultrasonography revealed a noncompressible portion of superficial dorsal vein of the penis, as well as the lack of venous flow signals. The patient was treated conservatively. Conclusion: Mondor’s disease of the penis is a rare clinical entity and a urologist should be aware of this condition.

Introduction Case presentation

Superficial-vein thrombosis was first described by Mondor in A 37-year-old man presented with a painful dorsal induration 1939 when it involved subcutaneous veins of the anterolateral of the penis for 4 days. The pain was of the throbbing type. thoracoabdominal wall [1]. The most commonly involved vessel There was no associated itching, discharge, hematuria, fever, is the thoracoepigastric vessel. In 1955, Braun-Falco described or dysuria. He denied any history of recent trauma, vigorous penile participation, and, in 1958, Helm and Hodge described sexual activity, or use of constriction devices. He also denied an isolated, superficial penile vein thrombosis [2,3]. Mondor’s any history of fever or lower urinary tract symptoms. A physical disease of the penis is an under-reported condition. Although it examination revealed a physically healthy man with a tender, is rare, proper diagnosis and consequent reassurance can help to cord-like swelling on the dorsal surface of the penis, which was dissipate the anxiety experienced by patients with the disease. extending from the glans penis up to the suprapubic area (Figure This case report describes the symptomatology, diagnosis, and 1). There was no associated inguinal lymphadenopathy. Routine treatment of thrombosis of the superficial dorsal vein of the blood tests and the coagulation profile were normal. Doppler penis. ultrasonography of the penis revealed a noncompressible, superficial dorsal vein, as well as the lack of venous flow

KEYWORDS: Mondor’s disease; Superficial thrombophlebitis; Conservative anagementm CORRESPONDENCE: Kapil Singla, Department of Urology, Vedanayagam Hospital, Coimbatore, Tamil Nadu, India 641 002 ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 87. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.05

UroToday International Journal case report UIJ Mondor’s Disease of the Penis: A Forgotten Entity Figure 1. Photograph showing cord-like thrombosed Figure 2. Doppler showing non compressible dorsal vein dorsal vein of penis. of penis with absent flow signals. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.05f1 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.05f2

signals (Figure 2). Provisional diagnosis of thrombosis of the Figure 3. Doppler showing complete restoration of blood superficial dorsal vein of the penis was made, and conservative flow in the dorsal vein. treatment was prescribed in the form of heparin ointment, as http://dx.doi.org/10.3834/uij.1944-5784.2012.02.05f3 well as nonsteroidal anti-inflammatory drugs (aceclofenac). The patient was advised to abstain from sexual activity and was advised to review at 1 month. On his first follow-up visit at 1 month, his physical examination revealed a complete resolution of the swelling. A repeat Doppler ultrasonography demonstrated restoration of normal blood flow in the dorsal vein (Figure 3).

Discussion

Mondor’s disease of the penis is an uncommon disease that usually involves the superficial dorsal veins. In 1939, Henri Mondor first described a sclerosing thrombophlebitis of the subcutaneous veins of the anterior chest wall, and, in 1955, Braun-Falco described phlebitis of the dorsal veins of the penis within the context of generalized phlebitis [1,2]. Isolated penile Mondor’s disease was first described in 1958 by Helm and Hodge [3]. Mondor’s disease is a benign and, usually, self-limited process. Patients complain of cord-like indurations, which are often painful, on the dorsal aspect of the penis, and this pain prolonged sexual abstinence, infection, pelvic tumors, and the can be constant or episodic. The etiology of this condition is constrictive elements used during certain sexual practices. Of usually unknown. Many predisposing factors can lead to the these factors, the trauma caused by sexual intercourse appears development of thrombosis of the dorsal vein of the penis. These factors all relate back to Virchow’s triad of endothelial to be the main etiologic factor. This may be due to stretching injury, stasis, and a hypercoagulable state. Various causative and torsion of the penile veins, causing endothelial denudation factors are there; e.g., penile trauma, excessive sexual activity, and the subsequent release of thromboplastic substances

UroToday International Journal case report UIJ Mondor’s Disease of the Penis: A Forgotten Entity that can activate the coagulation cascade [4]. Furthermore, 7. Nazir SS, Khan M. Thrombosis of the dorsal vein of the Mondor’s disease of the penis has also been reported after penis (Mondor’s Disease): A case report. Indian J Urol. long-haul flights [5], as an unusual manifestation of metastatic 2010;26:431-433. PubMed ; CrossRef pancreatic adenocarcinoma, and as an idiopathic condition. The diagnosis of the disease is mainly clinical, supplemented with Doppler ultrasonography [6]. The differential diagnosis includes sclerosing lymphangitis, Peyronie’s disease, and a fractured penis [7]. Treatment is essentially conservative. Several methods of treatment have been proposed for penile Mondor’s disease. Anticoagulation with aspirin, heparin, or other antiplatelet agents will not expedite healing and is not necessary to prevent additional thrombosis. Antibiotics can be used prophylactically. NSAIDs can be used for pain relief, as well as for their inflammatory action. Patients should also be informed about the avoidance of sexual intercourse or masturbation. In most of the cases, symptoms resolve completely within 6 to 8 weeks. In cases with no resolution, despite conservative treatment, thrombus excision or excision of the vein has to be done [4]. Such surgeries can relieve pain and diminish skin induration, and produce aesthetically pleasing results.

Acknowledgement

Dr. S Boopathy Vijaya Raghavan (Consultant Radiologist)

References

1. Mondor H, Tronculite Sons. Cutanee de la parvi thoracique antero-lateral. Mem Acad Chir.1939;65:1275-1278.

2. Braun-Falco O. [Clinical manifestations, histology and pathogenesis of the cordlike superficial phlebitis forms]. Dermatol Wochenschr. 1955;132:705-715. PubMed

3. Helm JD Jr, Hodge IG. Thrombophlebitis of a dorsal vein of the penis: report of a case treated by phenylbutazone (Butaolidin). J Urol. 1958;79:306-307. PubMed

4. Kraus S, Lüdecke G, Weidner W. Mondor’s disease of the penis. Urol Int. 2000;64:99-100. PubMed ; CrossRef

5. Day S, Bingham JS. Mondor’s disease of the penis following a long-haul flight. Int J STD AIDS. 2005;16(7):510-511. PubMed ; CrossRef

6. Yanik B, Conkbayir I, Oner O, Hekimoğlu B. Imaging findings in Mondor’s disease. J Clin Ultrasound. 2003;31(2):103-107. PubMed ; CrossRef

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Retroperitoneal Textiloma Mimicking an Adrenal Tumor

Rahul Devraj, Vedamurthy Pogula Reddy, Surya Prakash Vaddi, Ajit Vikram, Sreedhar D Dept of Urology and Renal Transplantation, Narayana Medical College, Nellore, India Submitted May 9, 2011 - Accepted for Publication July 25, 2011

ABSTRACT We describe a case with a perirenal-retained sponge presenting as an adrenal tumor in a patient who had undergone surgery for urolithiasis 10 years prior. It was incidentally diagnosed during an evaluation of left flank pain.

Introduction cortisol levels. A left retroperitoneal adrenalectomy was planned. During the operation, the left adrenal gland was normal and a Despite the widespread use of radio-opaque-labeled surgical 6 cm by 5 cm mass was seen lateral to the left suprarenal gland. sponges, retained sponges, or so-called textilomas from previous Dense adhesions were present between the mass, the left adrenal surgical procedures, are still causing diagnostic and therapeutic gland, and left kidney. The mass was excised in toto. A cut section problems. We present an unusual case and late discovery of a revealed a surgical sponge encapsulated by a thick, fibrous wall retained sponge, 10 years after pyelolithotomy, mimicking an (Figure 2). adrenal tumor.

Case report Discussion

A 52-year-old man was admitted to the hospital with the The abdomen, pelvis, and retroperitoneum are the most common complaint of left flank pain. He was a known hypertensive. He locations associated with retained surgical foreign bodies (RSFB) underwent left pyelolithotomy 10 years before this admission. [1]. RSFB in these anatomic areas can vary from an asymptomatic, On physical examination, a left flank incision scar and left flank retained foreign body detected accidentally on diagnostic imaging tenderness were noted. His serum creatinine was 1.8 mg. An ultrasound of the abdomen and a plain CT scan of the abdomen to sepsis, bowel obstruction, and fistula formation. Asymptomatic showed a left adrenal tumor (Figure.1). Biochemical evaluation soft-tissue mass suspicious for an abscess or a soft-tissue tumor revealed normal urinary catecholamine metabolites and serum has also been described as presenting features of RSFB in the

KEYWORDS: Retained sponge; Textiloma; Adrenal tumor CORRESPONDENCE: Vedamurthy Pogula Reddy, MCh, Dept of Urology and Renal Transplantation, Narayana Medical College, Nellore, Andhra Pradesh, India, 524 002 ([email protected]). CITATION: UroToday Int J. 2012 Feb;5(1):art 85. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.03

UroToday International Journal case report UIJ Retroperitoneal Textiloma Mimicking an Adrenal Tumor Figure 1. Plain CT scan of the abdomen showing the left Figure 2. Cut section of the specimen showing a surgical adrenal tumor. mop encapsulated by a thick fibrous wall. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.03f1 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.03f2

2. Roumen RM, Weerdenburg HP. MR features of a 24-year-old gossypiboma. A case report. Acta Radiol. abdomen, pelvis, and retroperitoneum [2,3]. 1998;39(2):176-178. PubMed

3. Bellin M, Hornoy B, Richard F, Davy-Miallou C, Fadel Y, Damage control operations for trauma or non-traumatic Zaim S, Challier E, Grenier P. Perirenal textiloma: MR etiologies can be associated with significant potential and serial CT appearance. Eur Radiol. 1998;8(1):57-59. complications. These procedures often utilize a large number of PubMed ; CrossRef surgical sponges to attain hemostasis. If these sponges are left in place or not exchanged for new sponges within 4 days of their 4. Rogers A, Jones E, Oleynikov D. Radio frequency initial placement, the risk of abdominal infection and/or abscess identification (RFID) applied to surgical sponges. Surg increases. Therefore, patients who have undergone abbreviated Endosc. 2007;21(7):1235-1237. PubMed ; CrossRef (damage control) laparotomy for trauma or non-trauma 5. Egorova NN, Moskowitz A, Gelijns A, Weinberg A, Curty indications may benefit from routinely scheduled roentgenograms J, Rabin-Fastman B, et al. Managing the prevention to help document and/or identify abdominal RSFB. More recently, of retained surgical instruments: what is the value the introduction of radio-frequency devices that are able to detect of counting? Ann Surg. 2008;247(1):13-18. PubMed ; appropriately radiolabeled surgical sponges has provided surgical CrossRef teams with another method of preventing RSFB [4]. Simultaneous use of radio-frequency labeled sponges, surgical counts, and/or radiographs will likely increase early detection of RSFB [5].

References

1. Mouhsine E, Halkic N, Garofalo R, Taylor S, Theumann N, Guillou L, et al. Soft-tissue textiloma: a potential diagnostic pitfall. Can J Surg. 2005;48(6):495-496. PubMed

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.03 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012

Teratoid Wilms Tumor in a Child: A Case Report

Jameel Hisham Bardesi, Ahmed Jalal Al-Sayyad King Abdulaziz University, Jeddah, Saudi Arabia Submitted October 15, 2011 - Accepted for Publication December 6, 2011

ABSTRACT

Teratoid Wilms is a very rare histopathological variant of Wilms tumors that is characterized by the predominance of heterologous components, and is described by many to be a nonaggressive, nonmetastatic tumor with a favorable prognosis. We report a case of a 4-year-old boy with a rare, aggressive metastatic variant of teratoid Wilms tumor. The boy presented with abdominal pain and a palpable abdominal mass. The computed tomography scan demonstrated a large, cystic, multiloculated left renal mass and a single left pulmonary metastasis. The patient had a 5-week course of neoadjuvant chemotherapy. As a result, the size of the metastatic lesion decreased, but there was no change in the size of the renal mass. Subsequently, a left radical nephrectomy and left pulmonary metastectomy were performed where the pathology report showed metastatic teratoid Wilms tumor. The patient received adjuvant chemotherapy and radiotherapy. One year following the initial surgery, the child developed bilateral pulmonary metastases where he is currently having an aggressive regimen of chemotherapy. Although teratoid Wilms has been described as a nonaggressive tumor with a favorable prognosis, it can present with more aggressive forms, with a tendency for metastasis.

Introduction has been described by many as a nonaggressive, nonmetastatic tumor with a favorable prognosis [1-3,5]. Review of 17— Wilms tumor is an embryonic tumor of mesodermal origin. It including 15 cases without metastases and 2 with metastases— is typically characterized by a display of a triphasic histological cases showed that 12 of them had no evidence of disease after pattern of blastemal, stromal, and epithelial cells. Heterologous receiving treatment [3]. Similar outcomes were reported in mesodermal components, such as adipose tissue, skeletal other cases [5,8]. Conversely, Myers et al. [8] stated that 50% muscle, cartilage, and neurological tissue, may be seen in small of those with teratoid Wilms presented at stage III or higher. foci throughout the neoplasm [1-3]. In 1984, a rare variant with They also reported an incidence of bilateral disease in 38%. heterologous predominance was described by Variend et al., According to the available data, a total of 3 cases of metastases who introduced the term “teratoid Wilms” [1]. Teratoid Wilms and 4 deaths—2 of them linked to progression—have been

KEYWORDS: Wilms tumor; Teratoid Wilms; Rare Wilms CORRESPONDENCE: Jameel Hisham Bardesi, King Abdulaziz University, Jeddah 21589, Saudi Arabia (jameelhbardesi@hotmail. com). CITATION: UroToday Int J. 2012 Feb;5(1):art 90. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08

UroToday International Journal case report UIJ Teratoid Wilms Tumor in a Child: A Case Report reported in those with teratoid Wilms [3,9,10]. We report a rare Figure 1. Multicystic, multiloculated left renal mass. case of 4-year-old boy with an aggressive metastatic variant of http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f1 teratoid Wilms tumor.

Case Report

A 4-year-old healthy boy presented with abdominal pain and a palpable abdominal mass. A computed tomography (CT) scan of the abdomen showed a huge multiloculated cystic mass involving the left kidney (Figures 1 and 2). A CT chest revealed a single metastasis in the left lung (Figure 3). A diagnosis of Wilms tumor of the left kidney with pulmonary metastasis was made. The patient underwent chemotherapy for 5 consecutive weeks. The patient received carboplatin (450 mg/m², IV, day 1 only) and etoposide (100 mg/m², IV, once daily for 5 days) in week 0, vincristine (0.05 mg/kg, IV, day 1 only), and actinomycin-D (15 mcg/kg, IV, once daily for 5 days) in week 1, and weekly vincristine (0.05 mg/kg, IV, day 1 only) throughout the second, third, and fourth weeks. As a result, the size of the metastatic lesion decreased while there was no change in the size of the renal mass. Subsequently, a left radical nephrectomy in conjunction with a left pulmonary metastectomy was performed. Cut sections of the mass were multicystic in appearance, with areas of necrosis and Figure 2. Coronal view of mass. hemorrhage, and showed no extension to the perinephric fat. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f2 Microscopically, sections of the kidney revealed a multicystic neoplastic process with wide areas of necrosis, hemorrhage, and hemosiderin-laden macrophages. The tumor was composed of nests and clusters of embryonal-looking cells, with enlarged hyperchromatic nuclei and occasional mitotic figures (Figure 4). Focal areas of spindle cells and smooth-muscle differentiation were also seen. Few cysts were lined by flattened epithelium while others were lined by stratified squamous epithelium and filled with keratin flakes (Figure 5). The left lung nodule was positive for metastases and had a blastemal component (Figure 6). A panel of immunohistochemical markers was performed on the lung nodule, including CK-Pan, vimentin, and WT-1. The tumor cells were positive for WT-1, focally positive for vimentin, and negative for CK-Pan (Figure 7). Postoperative radiotherapy (to the lung and abdomen) and chemotherapy in the form of actinomycin D (15 mcg/kg, IV, once daily for 5 days on weeks 12, 24, 36, 48, and 60 of initial treatment, and 30 mcg/kg day 1 only of weeks 6, 9, 18, 30, 42, 54, and 66 of initial treatment), vincristine (0.05 mg/kg, IV, day 1 only of weeks 6, 9, 28, 30, 42, 54, and 66, and 0.05 mg/kg, IV, once daily on days 1 and 5 in weeks 12, 24, 36, 48. 60), and doxorubicin (40 mg/m², IV, on day CT of the chest demonstrated multiple small focal lesions in 1 of weeks 6 and 9, and 60 mg/m², IV, on day 1 of weeks 18, 30, both lungs. There were no signs of local recurrence or residual 42, 54, and 66) were delivered. disease in the abdomen.

One year following the initial surgery, a routine follow-up The patient is currently alive 21 months after initial treatment.

UroToday International Journal case report UIJ Teratoid Wilms Tumor in a Child: A Case Report Figure 3. Left pulmonary nodule. Figure 4. Section from the primary tumor of the kidney http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f3 showing primitive blue round cells of Wilms tumor. Few tubules are seen showing hyaline casts (X 10, H & E stain). http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f4

He’s had repeated hospital admissions due to febrile neutropenia with chest infections. There has been no cytoreductive response on the metastatic nodules in the lungs so far. There’s been no rise to new metastatic lesions at other sites so far. Currently, a Figure 5. Squamous component of the tumor (X 20, H & regimen of chemotherapy is being given every 3 weeks, for a E stain). planned total of 6 courses. It is comprised of ifosfamide (1200 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f5 mg/m², IV, once daily for 5 days), carboplatin (450 mg/m², IV, day 1 only), and etoposide (100 mg/m², IV, once daily for 5 days).

Discussion

Teratoid Wilms is a rare histopathological variant of Wilms tumor, which is characterized by a predominance of heterologous components. A refined definition of teratoid Wilms was introduced by Fernandes et al. in 1988, proposing that the term be used to illustrate versus identify Wilms tumors with a heterologous component of more than 50% [4]. Searching PubMed, we found only 27 cases have been reported.

Teratoid Wilms has had clinical features similar to those of classical Wilms. It affects both sexes, with a mean age of 2.5 years. Abdominal masses and abdominal pain are the usual signs and symptoms [3,5]. This tumor has also been found to have diverse features, such as bilaterality, a tendency to extend into the collecting system, and association with nephroblastomatosis [6]. Park et al. [6] described the CT features of teratoid Wilms: It usually appears as a cystic renal mass with

UroToday International Journal case report UIJ Teratoid Wilms Tumor in a Child: A Case Report Figure 6. Section from the metastatic tumor to the lung Figure 7. Blastema cells showing positive nuclear staining showing sheets of primitive round cells invading the lung for WT-1 immunostaining (X 20). parenchyma (X 10, H & E stain). http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f7 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08f6

tumors less than 550 grams, and have a favorable histology. Those with recurrent Wilms tumors may be treated with multifocal, solid components containing fatty elements and aggressive chemotherapy, such as the ICE regimen (ifosfamide, occasional calcifications. carboplatin, and etoposide) or other regimens studied in clinical trials [11]. No specific treatment strategy has been Teratoid Wilms tumor and renal teratoma have been proposed to those with teratoid Wilms. Our patient, as well as hisologically similar. Beckwith proposed criteria to differentiate 2 other patients who had disease progression, received the ICE the 2 from each other. He stated that renal teratoids should be regimen, with mortality being the end result of the latter 2 [3]. intrarenal and show attempts of heterotopic organ formation [7]. Cytogenic analysis for the deletion of the short arm of Taking into consideration the diverse biological behavior chromosome 11 has been helpful in complicated cases [2]. of teratoid Wilms tumors, with most of them demonstrating a nonaggressive, nonmetastatic behavior, whereas some Although teratoid Wilms has been described as a nonaggressive, variants—including our case—exhibit an aggressive metastatic nonmetastatic tumor with a favorable prognosis [1-3,5], a total behavior, a question is raised of whether or not the later of 4 cases of metastases have been reported, including our case variant is truly teratoid Wilms or a different entity. Probably [3,10]. This rare variant of Wilms has been portrayed as chemo- a better description of the clinical, imaging, histopathological, resistant by many [1,2,10,9]. Neoadjuvant chemotherapy has immunohistochemical, and genetic characteristics of these been unable to produce a cytoreductive response in most tumors might help distinguish aggressive from nonaggressive cases [10,9]. This may be attributed to the well differentiated variants to predict prognosis. nature of the teratomatous elements in these cases [6,2]. In our patient, although downsizing could be achieved in the single Summary pulmonary metastasis, no size reduction was observed in the primary tumor with neoadjuvant chemotherapy. We present a rare, aggressive variant of teratoid Wilms tumor with metastasis. Disease progression was evident, even after The American Cancer Society guidelines for the treatment of neoadjuvant chemotherapy, radical nephrectomy, pulmonary Wilms tumor advise surgery, followed by chemotherapy with metastatectomy, and adujuvant chemoradiotherapy. Although actinomycin-D (dactinomycin) and vincristine for all stages, with teratoid Wilms has been described as a nonaggressive, the exception of those who are less than 2 years of age, have nonmetastatic tumor with a favorable prognosis, it can present

UroToday International Journal case report UIJ Teratoid Wilms Tumor in a Child: A Case Report with more aggressive forms, and with a tendency for metastasis. 10. Sultan I, Ajlouni F, Al-Jumaily U, Al-Ashhab M, Hashem Further investigations are needed to predict tumor behavior H, Ghandour K, et al. Distinct features of teratoid Wilms and designate treatment protocol for aggressive tumors. tumor. J Pediatr Surg. 2010;45(10):e13-19. PubMed ; CrossRef Acknowledgements 11. American Cancer Society. Wilms’ tumor treatmentby The authors gratefully acknowledge Professor Taha A Abdel- type and stage of Wilms’ tumor. http://www.cancer. Meguid, Professor of Urology, King Abdulaziz University, org/Cancer/WilmsTumor/DetailedGuide/wilms-tumor- Jeddah, Saudi Arabia, for his support. treating-by-stage. Published 2008. Accessed June 22, 2011.

References

1. Variend S, Spicer RD, Mackinnon AE. Teratoid Wilms’ tumor. Cancer. 1984;53(9):1936-1942. PubMed ; CrossRef

2. Gupta R, Sharma A, Arora R, Dinda AK. Stroma- predominant Wilms tumor with teratoid features: report of a rare case and review of the literature. Pediatr Surg Int. 2009;25(3):293-295. PubMed ; CrossRef

3. Köksal Y, Varan A, Akyüz C, Kale G, Büyükpamukçu N, Büyükpamukçu M. Teratoid Wilms in a child. Pediatr Int. 2007;49(3):414-417. PubMed

4. Fernandes ET, Parham DM, Ribeiro RC, Douglass EC, Kumar AP, Wilimas J. Teratoid Wilms’ tumor: the St Jude experience. J Pediatr Surg. 1988;23(12):1131-1134. PubMed ; CrossRef

5. Song JS, Kim IK, Kim YM, Khang SK, Kim KR, Lee Y. Extrarenal teratoid Wilms’ tumor: two cases in unusual locations, one associated with elevated serum AFP. Pathol Int. 2010;60(1):35-41. PubMed ; CrossRef

6. Park CM, Kim WS, Cheon JE, et al. Teratoid Wilms tumor in childhood: CT and ultrasonographic appearances. Abdom Imaging. 2003;28(3):440-443. PubMed ; CrossRef

7. Beckwith JB. Wilms’ tumor and other renal tumors of childhood. Hum Pathol. 1983;14(6):481-492. PubMed ; CrossRef

8. Chowhan AK, Reddy MK, Javvadi V, Kannan T. Extrarenal teratoid Wilms’ tumour. Singapore Med J. 2011;52(6):e134- 137. PubMed

9. Myers JB, Dall’Era J, Odom LF, McGavran L, Lovell MA, Furness P III. Teratoid Wilms’ tumor, an important variant of nephroblastoma. J Pediatr Urol. 2007;3(4):282-286. PubMed ; CrossRef

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.08 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 5 - February 2012 Treatment of Post, High-Intensity-Focused Ultrasound Urethral Stricture with Novel Long-term Stent

Omri Nativ, Sarel Halachmi, Boaz Moskovitz, Ofer Nativ Department of Urology, Bnei-Zion Medical Center, Haifa, Israel Submitted November 4, 2011 - Accepted for Publication December 13, 2011

ABSTRACT

Urethral strictures (US) can be recurrent chronic illnesses leading to severe side effects and poor quality of life. Several options to treat US exist, including repeated dilatations, stents, and open surgery. A urethral stent is a good, minimally invasive option but has major limitations, such as stent migration, mucosal growth, and incontinence, especially for bladder-neck strictures. Herein, we describe a new stent that, due to its design, may solve some of the above-mentioned problems, enabling long-term use and safe removal.

Case Report of the urethra at the level of the prostatic urethra/bladder-neck area. The patient was referred for an Allium round posterior A 66-year-old presented to us who, 3 years earlier, had undergone urethral stent (RPS) placement. high-intensity-focused ultrasound (HIFU) treatment for organ- confined (Gleason score 3+4) prostate cancer. Approximately Description of the Allium RPS Stent 3 months after the procedure, he presented to his local urologist with progressive obstructive voiding symptoms that The Allium RPS system is indicated for the management of were managed endoscopically via visual internal urethrotomy, bladder outlet obstruction in adult males. The stent, presented followed by a transurethral resection of stenotic scar tissue. in Figure 2 and Figure 3, is a large-caliber, long-term, fully Afterwards, he underwent repeated endoscopic treatment covered stent made of a self-expandable Nitinol skeleton for restenosis every 10 to 12 weeks. A typical pre- and post- covered with a thin membrane of biocompatible and biostable treatment endoscopic view is shown in Figure 1. Upon arrival at copolymer. The entire skeleton of the RPS is made of a single our medical center, the patient underwent a urinary ultrasound Nitinol wire. The copolymer covers the entire stent body and its that revealed a normal upper urinary tract, small prostate, and anchor to prevent intraluminal tissue ingrowth. It has a single 240 ml of post-void residual urinary volume. Uroflowmetry length of 40 mm, a 45 Fr round cross-section, and is composed demonstrated an obstructive pattern with maximal urinary of 3 segments: body (40 mm), anchor (14 mm), and trans- flow of 5.6 ml/sec. A cystoscopy demonstrated a tiny opening sphincteric wire, which connects the body to the anchor.

KEYWORDS: High-intensity-focused ultrasound; Urethral stricture; Long-term urethral stent CORRESPONDENCE: Sarel Halachmi, MD, Department of Urology, Bnai-Zion Medical Center, Haifa, Isreal (Sarel.Halachmi@b-zion. org.il). CITATION: UroToday Int J. 2012 Feb;5(1):art 92. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10

UroToday International Journal case report UIJ Treatment of Post, High-intensity-Focused Ultrasound Urethral Stricture with Novel Long-term Stent Figure 1. Typical endoscopic view of the bladder neck Figure 2. Allium round posterior stent (RPS) demonstrating area of the case presented before and after transurethral body, trans-sphincter wire, and anchor. resection. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10f2 http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10f1

Stent Insertion

The procedure was done under spinal anesthesia with the patient in the dorsal lithotomy position. Initially, a retrograde urethrography was performed to evaluate the length of the structure and to mark the urethral sphincter’s exact location. This was followed by a cold-knife visual internal urethrotomy at the 5, 7, and 12 o’clock positions. After dilating the occluded prostatic urethra and bladder neck, the RPS was inserted using a special delivery system (Figure 4), which was done under fluoroscopy. Once located in the target area, the delivery system Figure 3. Allium round posterior stent (RPS) demonstrating was gradually removed from the urethra and, simultaneously, body, trans-sphincter wire, and anchor. the stent was released, leaving the body in the prostatic area http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10f3 and the anchor in the bulbar segment. To verify the stent’s patency, a second urethrography was performed (Figure 5), and at the end of the procedure, no catheter was left.

Follow-up

Postoperatively, the patient reported mild perineal discomfort with few episodes of urge incontinence, but no bleeding. After 2 weeks, the patient was fully continent for the next 12 months. One episode of urinary tract infection occurred 4 months after the stent insertion, which was controlled by a short course of oral antibiotics. At 1 year, and under local anesthesia, the RPS stent was removed endoscopically by simply pulling its anchor end, situated in the bulbar urethra, using standard biopsy forceps. Now, 8 months after stent removal, the patient voids spontaneously, emptying his bladder adequately with complete urinary control.

UroToday International Journal case report UIJ Treatment of Post, High-intensity-Focused Ultrasound Urethral Stricture with Novel Long-term Stent Discussion Figure 5. Showing the passage of contrast material via the stent. In recent years, a number of ablative therapies have been http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10f5 introduced for the management of localized prostate cancer, including cryosurgery, high-intensity-focused ultrasound (HIFU), radio frequency ablations, and photodynamic therapy, which are in various stages of evolution, evaluation, and clinical implication. HIFU treatment relies on the physical properties of ultrasound, which allows it to be brought into small focus at the target tissue. When the energy density at the focus is sufficiently high, thermal tissue damage occurs through coagulative necrosis [1]. Despite being a minimally invasive procedure, HIFU treatment is associated with morbidity. The most common complications after HIFU treatment are stress urinary incontinence, urinary tract infection, urethral/bladder neck stenosis or strictures, and erectile dysfunction. In a recent literature review performed by the French association of urology, the rate of urethral stricture reaches up to 31% [2].

Figure 4. Showing the expanded stent located at the prostatic urethra. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10f4

With similar results (30.2%), the intervention rate for stricture, or retained necrotic-tissue removal, was described by Ahmed HU et al. who summarized the first 172 men treated in the UK. About half of the strictures are managed by urethral dilation on local anesthesia, while the other half require anesthesia and bladder-neck incision and/or resection [3]. The HIFU device enables transformation of the energy delivered into heat reaching between 56°C up to 90°C. Such temperatures can cause urethral strictures due to protein denaturation. Some of them may involve the periurethral tissue, resulting in extensive fibrosis giving rise to resistant urethral stricture [4]. Most often, such strictures are initially managed either by balloon dilation or visual internal urethrotomy. Unfortunately, for some of the patients, early treatment failure is observed, and after the third endoscopic treatment, the success rate is extremely low [5]. Alternative endoscopic options for the management of stenotic bladder neck areas include endoscopic resection using either cold-knife or laser energy, combined with steroid or mitomycine C injection to inhibit scar regrowth [6,7]. The transurethral resection of scar tissue at the bladder neck provides a modest chance of success in treating recurrent stenosis. After endoscopic technique failure, a patient may be offered an open surgical reconstruction of the scar tissue. This treatment

UroToday International Journal case report UIJ Treatment of Post, High-intensity-Focused Ultrasound Urethral Stricture with Novel Long-term Stent option is technically demanding and would typically leave the 3 Ahmed HU, Zacharakis E, Dudderidge T, Armitage JN, patient incontinent. A completely different approach is the use Scott R, Calleary J, et al. High-Intensity-Focused Ultrasound of an intraurethral stent, which may be either permanent or in the treatment of primary prostate cancer: the first UK temporary. Elliot SP et al. reported their experience with 10 series. Br J Cancer. 2009;101(1):19-26. PubMed ; CrossRef cases, using the UroLume permanent stent. Unfortunately, this stent, if placed near the trigon, might cause urinary irritative 4 Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters symptoms, can be occluded by calcification or by scar tissue, CA. Campbell-Walsh Urology. 9th ed. Philadelphia, Pa: and, once inserted, the endoprosthesis is extremely difficult to Saunders Elsevier; 2007:1023-1054. remove, requiring an open surgical approach [8]. Henderson et al. described their experience with the Spanner temporary 5 Heyns CF, Steenkamp JW, De Kock ML, Whitaker P. urethral stent to relieve bladder outflow obstruction after Treatment of male urethral strictures: is repeated dilation prostate brachytherapy [9]. Although they were not treating or internal urethrotomy useful? J Urol. 1998;160(2):356- resistant strictures, and no prior endoscopic treatment was 358. PubMed ; CrossRef performed, they reported early (after 7 days) stent removal due to severe discomfort, while the remaining 60% were able to 6 Vanni AJ, Zinman LN, Buckley JC. Radial Urethrotomy and hold the stent for the planned 30 days. Intra-lesion Mitomycin C for the Management of Recurrent Bladder Neck Contractures. J Urol. 2011;186(1):156-160. In the case presented, we describe successful management PubMed ; CrossRef of post-HIFU, severe bladder-neck and prostatic urethral strictures using a new temporary urethral stent called the 7 Eltahawy E, Gur U, Virasoro R, Schlossberg SM, Jordan GH. Allium RPS. It is a temporary long-term and temporary self- Management of recurrent anastomotic stenosis following retaining intraurethral stent. Insertion of the stent is simple, radical prostatectomy using Holmium laser and Steroid and its positioning is under fluoroscopy while the removal can injection. BJU Int. 2008;102(7):796-798. PubMed ; CrossRef be done as an outpatient procedure under local anesthesia. Being covered by a thin copolymer, intraluminal ingrowth 8 Elliott SP, McAninch JW, Chi T, Doyle SM, Master VA. was prevented, allowing the stenotic area to remain open Management of severe urethral complications of prostate for the duration of 1 year in which no bladder discomfort or cancer therapy. J Urol. 2006;176(6 pt 1):2508-2513. PubMed incontinence were reported. During 7 months of post-stent ; CrossRef removal follow-up, no outflow obstruction developed and the patient is able to completely empty the bladder. This favorable 9 Henderson A, Laing RW, Langley SE. A Spanner in the outcome may be related to an extended duration (1 year) of the works- the use of a new temporary urethral stent to relieve stent that enabled bladder neck remodeling and stabilization bladder outflow obstruction after prostate brachytherapy. of the periurethral scar tissue. Finally, this minimally invasive Brachytherapy. 2002;1(4):211-218. PubMed ; CrossRef treatment alternative is more efficient than current endoscopic treatments, is safe, tolerable by the patient, and more cost- effective.

References

1. Illing RO, Leslie TA, Kennedy JE, Calleary JG, Ogden CW, Emberton M. Visually directed HIFU for organ confined prostate cancer – a proposed standard for the conduct of therapy. BJU Int. 2006;98(6):1187-1192. PubMed ; CrossRef

2 Rebillard X, Soulié M, Chartier-Kastler E, Davin JL, Mignard JP, Moreau JL, Coulange C, et al. High-intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology. BJU Int. 2008;101(10):1205-1213. PubMed ; CrossRef

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 5 / Iss 1 / February / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.10 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ® UIJUroToday International Journal www.urotodayinternationaljournal.com Volume 4 - December 2011 Ureteral Diverticulum in Adults: Diagnostic Problems and Therapeutic Implications

Sallami Satáa, Sami Ben Rhouma, Ali Horchani Department of Urology, La Rabta Hospital-University, Tunis, Tunisia Submitted September 1, 2011 - Accepted for Publication October 4, 2011

ABSTRACT Ureteral diverticulum is a rare anomaly and often gives rise to urinary complications. We report a case of a woman with bifid renal pelvis. She had a stone in the lower pelvis with cystic dilation of the upper ureter.

Introduction film (Figure 1) and renal ultrasonography showed a stone on the right renal pelvis. On intravenous pyelography, the left True ureteral diverticulum is a rare anomaly and often gives rise kidney, pelvicalyceal system, and the bladder looked normal. to urinary complications [1].

The right kidney had a duplex system. The lower pelvis contained Its etiology remains unknown, although many theories have a stone of 3 cm in size with mild hydronephrosis, and the ureter been proposed. It may be congenital or acquired [2]. Congenital of the lower pelvis showed an outpouching (Figure 2). diverticula of the ureter are exceptional and only a few cases were reported in the literature. The patient underwent a surgical diverticular resection

Herein we present a case with a view of surgical treatment and with removal of the pelvic stone, and an end-to-end ureter long-term results. anastomosis with the insertion of a double J catheter.

CASE REPORT The pathological study concluded true ureteral diverticulum, with all the layers of a ureteral wall and with no sign of A 36-year-old woman, with no significant medical history, malignancy. The recovery period was uneventful. The double presented for chronic right lumbar pain. Her physical J catheter was removed 4 weeks later. By the 26-month examination was unremarkable. The urinalysis was normal and follow-up, the pain completely disappeared and radiological so were the blood-count cells and plasma creatinine. The KUB investigations didn’t reveal any anomaly.

KEYWORDS: Diverticulum; Ureter; Abnormalities; Stone CORRESPONDENCE: Sallami Satáa, MD, Department of Urology, La Rabta Hospital-University, Tunis, Tunisia (sataa_sallami@ yahoo.fr). CITATION: UroToday Int J. 2011 Dec;4(6):art 86. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.04

©2012 Digital Science Press, Inc. http://www.urotodayinternationaljournal.com UIJ / Vol 4 / Iss 6 / December / http://dx.doi.org/10.3834/uij.1944-5784.2012.02.04 ISSN 1944-5792 (print), ISSN 1944-5784 (online) ®

UroToday International Journal case study UIJ Ureteral Diverticulum in Adults: Diagnostic Problems and Therapeutic Implications Figure 1. KUB film: A right renal stone. Figure 2. IVP: A lower pelvis stone with mild hydronephrosis http://dx.doi.org/10.3834/uij.1944-5784.2012.02.04f1 and an outpouching of the corresponding proximal ureter (see arrow). http://dx.doi.org/10.3834/uij.1944-5784.2012.02.04f2

DISCUSSION diverticular formation or, at least, in leading to its discovery [5]. Lindeman, in 1895 [6], reported that obstructing a rabbit Duplicated and bifid ureters constitute the most common ureter might produce true diverticula, which supports this ureteral malformations, but ureteral diverticulosis is an theory. Previous reports have described a positive association uncommon urinary abnormality [1,3]. Their association on the of vesicoureteral reflex, urolithiasis, fibroepithelial polyps, same side is possible, but it remains extremely rare [1]. and trauma with diverticula [2]. The most plausible view is considering the diverticulum as a secondary compensatory In 1808, Pepere described the first case of ureteral diverticula structure following a congenital stricture that formed either in found at autopsy [3]. Their etiology and their clinical significance utero or shortly after [3]. are still debated. Barrett and Malek [4], through a series of 12 patients with ureteral diverticulum, showed that associated Although nephritic colic, hematuria, and upper urinary tract renal or ureteral diseases may potentiate the development infections may be the presenting symptoms, ureteral diverticula of a diverticulum. Infection has been implicated in causing are usually asymptomatic [7], as in our case. Our patient

UroToday International Journal case study UIJ Ureteral Diverticulum in Adults: Diagnostic Problems and Therapeutic Implications Figure 3. By open surgery, we performed a diverticular Figure 4. Three different layers of the ureteral resection (diverticulectomy) with removal of the pelvic diverticulum after excision. stone, and end-to-end ureter anastomosis with insertion http://dx.doi.org/10.3834/uij.1944-5784.2012.02.04f4 of a double J catheter. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.04f3

remained asymptomatic until adult age. Actually, this anomaly complications ensue. Infection is the most common complication, is accidentally discovered via radiological investigations in but several cases of stone formation in a diverticulum have patients with lumbar pain or renal colic more and more. They been reported, as in our case [5], and other cases that include are occasionally detected during urography or retrograde ureteral strictures. A case of transitional-cell carcinoma in a pyelography, they appear as small specula or as a saccade wall diverticulum of the lower ureter was described [9]. outpouching, they are singular or more often in multiples, and they are mostly limited to the upper third of the ureter (5). The principal aim of treatment is to release the obstruction of the collecting system and the creation of a patent ureter Gray and Skandalakis had classified the diverticula of the ureter with ureteroscopic maneuvers or open surgery. A nephrectomy into 3 categories: 1) abortive ureteral duplications (blind- is rarely necessary and should only be applied to infected ending bifid ureters), 2) true congenital diverticula containing and nonfunctioning kidneys [2,4]. Our patient underwent all tissue layers of the normal ureter, and 3) acquired diverticula a diverticular resection with extraction of the stone by open representing mucosal herniations [8]. Congenital diverticula surgery. In all cases, operated or nonoperated patients, possess the histological layers of the ureter (mucosa, muscularis, the radiological follow-up is mandatory to detect later and adventitia), and they connect with the other ureter complications, such as secondary ureteral stenosis. at an acute angle. Through these structural features, they are distinguished from acquired diverticula (post traumatic CONCLUSION or infective), which have no ureteric wall proper [1]. The histopathologic diagnosis in our case revealed these different Ureteral diverticulum is a very rare urinary abnormality layers, which are typically seen in congenital cases. associated with an increased risk of local complications. Diagnosis is made during radiological investigations, especially When diagnosed, treatment of the diverticulum depends on the intravenous pyelogram. The treatment, if indicated, is the clinical presentations [2]. Treatment is indicated if the surgical. diverticulum is thought to be the cause of symptoms or if

UroToday International Journal case study UIJ Ureteral Diverticulum in Adults: Diagnostic Problems and Therapeutic Implications References

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