Issue 4: August 2009

UIJ Volume 2 Issue 4 August 2009

Letter from the Editor - August 2009

Dear Colleagues,

Progress in urology, like in any medical field, is dependent on a continuous accumulation of new knowledge. Every piece of new information, from brief case studies to large clinical trials, adds to our knowledge base and helps the profession grow. The editorial team of UroToday International Journal is grateful to the authors who shared their work in this issue and to the reviewers who ensured its scholarship.

Clinical trials of medications are among the most essential types of research, because they help to dictate treatment standards. Olshansky and his colleagues (Validation of the Differential Cardiovascular Effects of the Antimuscarinic Agents Darifenacin and Tolterodine in a Randomized, Placebo-Controlled, 3-Way Crossover Study) share the results of a well-designed investigation. They validated the results of a previous study showing that tolterodine caused an increase in heart rate (HR) and decrease in heart rate variability (HRV) in healthy older adults, whereas darifenacin did not. Both increased HR and decreased HRV have been associated with increased mortality rates in the general population, particularly in patients with cardiovascular morbidities. Because antimuscarinics are the recommended treatment of patients with the overactive bladder (OAB) syndrome, and these patients have a high prevalence of cardiovascular morbidity, a difference of 2-5 beats per minute in mean HR over 24 hours and a decrease in HRV may be of clinical importance. Physicians who prescribe antimuscarinics will be interested in these findings.

Review articles can provide useful updates on current clinical practice. Westerling’s review (Bladder Pain: Clinical Assessment and Treatment) provides thorough, practical information for any professional involved in the physiology, assessment, and pharmacological or nonpharmacological treatment of bladder pain. Patients with long-term bladder pain often have comorbidities and medications that can complicate management. They may benefit from a multi-disciplinary team approach. Westerling reminds us that quality of life may improve dramatically if these patients are seen by a pain specialist early in the treatment sequence, rather than waiting until the pain is out of control.

The August issue contains many other articles of interest, including: (1) the very timely topic of a gene expression test for prostate cancer, written by Guyon and colleagues; (2) the continuous bladder irrigation model developed by Norman and Connor that shows urethral outflow with and without the addition of suprapubic inflow, using suprapubic catheters of different size combinations; and (3) the use of bacillus Calmette-Guerin therapy with cauterization of 10 mm of the tumor margin in patients with bladder cancer−a management protocol that showed promising results for Falahatkar and colleagues. Finally, Al-Sameraaii and Bowkett remind us of dangers to our children that may reside in the most unlikely places, including their toys.

Kind regards,

K-E Andersson

Efficacy of Bacillus Calmette-Guerin (BCG) Therapy and Cauterization of the Tumor Versus BCG Therapy Without Cauterization for Superficial Bladder Cancer


INTRODUCTION: Bladder cancer recurrence occurs in 30-80% of cases after resection depending upon the grade, stage and number of tumors. The rate of recurrence for superficial bladder cancer is 70%. Cauterization is known to destroy malignant cells. Therefore, the authors studied the efficacy and tumor recurrence rate of bacillus Calmette-Guerin (BCG) therapy with cauterization of 10 mm of the tumor margin versus BCG therapy without cauterization.

METHODS: The authors reviewed files of 60 patients, including 30 patients with cauterization (group 1) and 30 patients without cauterization (group 2). Patients were referred from March 2006 to June 2008 with primary stage Ta, T1, and T2a, grade G1 to G3 transitional cell carcinoma (TCC) of the bladder. All patients were treated by transurethral resection of the tumor (TUR-BT). The 2 groups did not differ significantly in age and sex or in tumor grade, location, and size. Grade, stage, location and size of tumors with recurrence were compared.

RESULTS: There were no significant differences between the two groups in stage, location, and size of tumors. Tumors returned in 25 of the 60 patients (9 from group 1; 16 from group 2). The group difference in recurrence rate was not statistically significant (P = .06). The mean time of tumor recurrence was 21 months and 13 months in groups 1 and 2, respectively. Group 1 had a significant delay in tumor recurrence when compared with group 2 (P = .01). Most of the tumors that recurred were from patients with grade 1 and grade 2 tumors (5 patients in group 1; 15 in group 2). Four out of 5 patients with grade 3 tumors in group 1 and the only patient with a grade 3 tumor in group 2 had recurrence. The recurrence rate for low-grade tumors in group 1 was significantly less than in group 2 (P = .02).

CONCLUSIONS: Cauterization of the tumor margins combined with BCG therapy appears to be useful for reducing recurrence in patients with grade 1 and grade 2 bladder tumors. Cauterization also resulted in a longer period of time before recurrence.

KEYWORDS: Bladder tumor; Cauterization; BCG therapy, Bladder cancer recurrence

CORRESPONDENCE: Siavash Falahatkar M.D., Guilan University of Medical Sciences, Urology Research Center, Razi Hospital, Sardare Jangal Street, Rasht, Guilan 41448, Iran ().

CITATION: UroToday Int J 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.01



New Prognostic Factors in Fournier’s Gangrene: A 10-Year Experience


INTRODUCTION:Fournier's gangrene is a rapidly progressing infection of the male genitalia, including the anal and perianal region and usually extending to the abdominal wall. The objective of the present investigation was to study the epidemiologic and clinical reports of patients with Fournier’s gangrene in order to evaluate the prognostic factors of the disease.

METHODS: The patients were referred to Ghaem hospital from 1998-2008. Their files were reviewed for: (1) laboratory parameters of urea, creatinine (Cr), hematocrit (Hct), white blood cell (WBC), albumin (Alb), sodium (Na), Calcium (Ca), and potassium (K); (2) probable risk factors (eg, diabetes); (3) ulcer microbiology; and (4) the extent of the gangrene.

RESULTS: There were 71 patients with a mean age of 60.9 years (SD = 17.02). The time between onset of symptoms and referral to a health care unit was 6.7 days (SD = 5.25). The source of infection was the skin in 25 patients (35%), urogenital in 34 patients (48%), and rectal in 12 patients (17%). The anorectal source was responsible for 11 out of 16 deaths. Diabetes was a predisposing factor in 39.4%.

The patients were divided in 2 groups: the survival group (n = 55) and the mortality group (n = 16). The survival group had a significantly higher socioeconomic status, shorter mean time between the onset of the illness and referral to a health clinic, lower percentage of gangrene involvement, fewer required debridements, and higher mean Alb and Ca and lower mean urea laboratory values (P < .05). There were no other significant between-group differences for the remaining variables.

CONCLUSION: The authors compared the data in the present study with data from the Laor Fournier's Gangrene Severity Index. None of the conventional indices (temperature, heart rate, respiratory rate, Hct, Cr, WBC, Na, K) were found to be significantly different when the mortality and survival group were compared in the present study. The authors recommend new prognostic criteria for Fournier’s gangrene: (1) time between onset of the symptoms and referral to the hospital; (2) source of infection; (3) extent of the gangrene; (4) laboratory results of Alb, urea, and Ca; and (5) the number of required debridements.

KEYWORDS: Fournier's gangrene; Laor Fournier's gangrene severity index; Prognosis; Risk factors

CORRESPONDENCE: Mahmood Molaei, M.D., Department of Urology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran ().

CITATION: Urotoday Int J. 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.02



Validation of the Differential Cardiovascular Effects of the Antimuscarinic Agents Darifenacin and Tolterodine in a Randomized, Placebo-Controlled, 3-Way Crossover Study


INTRODUCTION:Previous studies have demonstrated that antimuscarinics used for the treatment of overactive bladder (OAB), such as tolterodine and darifenacin, exert differential effects on heart rate (HR) and HR variability (HRV). OAB is a chronic symptomatic condition of high prevalence in older patients with cardiovascular (CV) comorbidities. Physicians prescribing these medications should take into consideration their specific effects on the parasympathetic control of the heart.

OBJECTIVE: The primary objective was to detect if there was a difference between tolterodine and darifenacin in change from baseline in mean HR over 24 hours during once-daily administration of these compounds in healthy participants. The protocol was designed to confirm results from a previous study.

METHODS:This was a 3-way crossover, placebo-controlled, double-blind study in healthy participants of similar age to OAB patients (≥ 50 years). Participants were randomized to one of 6 possible treatment sequences and consecutively received once-daily tolterodine 4 mg, darifenacin 15 mg, and matched placebo for at least 7 days in separate treatment periods. Electrocardiogram monitoring (Holter) for 24 hours was used to assess changes in mean HR and HRV between treatment arms

RESULTS: Tolterodine but not darifenacin significantly increased mean HR over 24 hours compared with darifenacin (2.24 beats per minute [bpm], P = .0004) and placebo (1.84 bpm, P = .0037). In contrast, darifenacin did not significantly alter HR compared with placebo (–0.40, P = .5219). Overall, HRV over 24 hours decreased with tolterodine but not with darifenacin or placebo.

CONCLUSION: Tolterodine increased HR and reduced HRV compared with darifenacin and placebo in healthy participants aged ≥ 50 years. Because increased HR and decreased HRV are associated with increased CV risk and patients with OAB often have CV comorbidities, careful selection of antimuscarinic treatment for OAB patients may be warranted.

KEYWORDS: Antimuscarinic; Cardiovascular effects; M3 selectivity

CORRESPONDENCE: Brian Olshansky, MD, Professor of Medicine, University of Iowa Hospitals, 4426a JCP, 200 Hawkins Drive, Iowa City, Iowa 52242, USA ().

CITATION: Urotoday Int J. 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.07



Neuropathic Symptoms After Surgery Using Transobturator Tape for Stress Incontinence


A 40-year-old female patient with frequency of micturition and stress incontinence had surgery using transobturator tape (TOT). The surgical procedure was uncomplicated but the patient developed symptoms of groin pain, loss of sensations in the legs, and inability to stand or bear weight 48 hours postoperatively. Neurological assessment did not reveal any motor loss, although reduced sensations in the right thigh persisted for a few days. Pelvic collection, mesh infection, and exposure were excluded. Physiotherapy and analgesia were administered and her symptoms diminished. No residual symptoms were present at 4 and 8-week follow-up evaluations.

KEYWORDS: Transobturator; Groin pain; Neuropathy; Obturator nerve damage

CORRESPONDENCE: Dr. Asma Farrukh MRCOG, Derby Hospitals, Department of Obstetrics and Gynaecology, Uttoxeter Road, Derby, DE223NE, United Kingdom ().

CITATION: Urotoday Int J. 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.05



Does the Addition of Extra Inflow From a Suprapubic Catheter Improve Continuous Bladder Irrigation Through a 3-Way Transurethral Catheter?


INTRODUCTION: Continuous bladder irrigation (CBI) is often used to help manage hematuria and might be optimized by adding suprapubic inflow to increase urethral outflow. The objective of the present investigation was to develop an experimental model that would reliably measure urethral outflow through a 3-way transurethral catheter (UC) with and without the addition of suprapubic inflow using a variety of suprapubic catheters (SC) of different size combinations (Bard).

METHODS: A 1 L intravenous bag (Hospira Inc; Lake Forest, IL) was modified by inserting a 3-way UC into its outflow spigot and a 2-way SC into the front of the bag. The urethral outflows for each size of UC were measured in various combinations of 18F, 20F, 22F, and 24F 3-way UC with and without added inflows from 12F, 14F, and 16F 2-way SC. Water was used as the irrigant for both the urethral and suprapubic catheters and was drained by gravity from 3 L bags from a height of 140 cm. Urethral outflow was measured with a Dantec Urodyn 1000 uroflowmeter. Each run was done 5 times using outflows of at least 150 cc over at least 75 seconds. Means were compared by paired t test.

RESULTS: Three-way 18F, 20F, and 22F UC showed no significant or minimal improvement in outflows by adding 12F, 14F, or 16F suprapubic inflows. None of these 3-way catheters were able to handle the extra inflow from a 16F suprapubic catheter and the "bladder" became overly distended (OD). Three-way 24F UC showed maximal improvement in outflow when combined with 14F or 16F suprapubic inflows; OD was not a problem.

CONCLUSION: Additional inflow from a 14F or 16F SC will maximally increase urethral outflow by at least 3.6 cc/second only when combined with a 24F 3-way UC.

KEYWORDS: Continuous bladder irrigation; Transurethral catheter; Suprapubic catheter; Three-way catheter; Hematuria.

CORRESPONDENCE: Dr. Richard W Norman, Suite 620, 5991 Spring Garden Road, Halifax, Nova Scotia, B3H 1Y6, CANADA ()

CITATION: UroToday Int J 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.09



Bladder Pain: Clinical Assessment and Treatment


INTRODUCTION: Bladder pain may arise due to infection, inflammation, trauma, cancer, or unknown reasons. Bladder pain may be acute, long term and/or associated with other symptoms and syndromes. The treatment of bladder pain must consider both the pain and the function of the bladder.

METHODS: The definition, physiology, assessment, pharmacological treatment, and nonpharmacological treatment of bladder pain are reviewed and discussed. Three cases of complex bladder pain are presented.

RESULTS: Bladder pain is a symptom, not a disease. There is no single therapy that is helpful for all patients. Multimodal pain therapy that is tailored to the patient's present situation, genetics, ongoing treatment, and previous treatment(s) may reduce pain and improve quality of life.

CONCLUSION: Multidisciplinary evaluation and referral to a pain specialist should be considered for patients with complicated bladder pain with or without associated long-term pain problems. Patients with complex bladder pain may benefit from a consultation and second opinion from a pain specialist early in the course of the workup and not as a last measure when everything else has failed. Multidisciplinary pain teams with pain specialists should be part of the network available for clinicians who provide care for patients with complex pain problems.

KEYWORDS: Bladder pain; Assessment of pain; TENS; Pharmacology; Analgesia

CORRESPONDENCE: Dagmar Westerling, M.D. Ph.D., Acute Pain Unit, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem NC, 27157, USA ().

CITATION: UroToday Int J 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.03



Pilot Study on the Comparative Assessment of Maximum Bladder Capacity for the Diagnosis of Interstitial Cystitis: NaCl 0.9% Versus 0.2M KCl


INTRODUCTION: A deficiency in the glycosaminoglycan (GAG) layer alters bladder urothelial permeability, mainly to potassium ions, in patients with interstitial cystistis (IC). The potassium sensitivity test (PST) causes bladder discomfort after instillation of a 0.2 molar potassium chloride solution (0.2 M KCl). The objective of the present study was to assess maximum bladder capacity (Cmax) using a 0.2 M KCl solution compared with 0.9% sodium chloride (NaCl) in patients with IC, in order to achieve diagnosis.

METHODS: The authors studied 17 female patients diagnosed with IC, based on criteria from the National Institute of Diabetes and Digestive and Kidney Diseases. Patients completed the Pelvic Pain and Urgency/Frequency (PUF) questionnaire. Cystometry was performed first with a 0.9% NaCl solution, followed by 0.2M KCl soon after. The desire to void and Cmax were measured in both cystometries. After undergoing tests with each solution, the patients evaluated pain and urgency by using a visual numeric scale.

RESULTS: All patients presented a larger decrease in Cmax when using KCl, compared with NaCl. The median Cmax decrease was 32.8% (range, 7.69% - 57.8%). A decrease in Cmax > 30% was observed in 9 patients; the remaining 8 patients had a decrease < 30%. All patients reported greater discomfort with the use of 0.2M KCl solution. The visual numeric scale score for pain revealed a mean value of 2.41 for the NaCl solution and 4.52 for KCl, with 5 representing maximum pain. The average PUF score was 23.76 (range, 18-33). When the PUF score was compared between patients with a decrease in Cmax > 30% and < 30%, no statistically significant difference was found.

CONCLUSION: PST is a well-tolerated alternative when evaluating both the increased sensitivity to potassium and the diagnosis of IC, considering the reduction in Cmax. The PUF score has no direct correlation with the PST positivity.

KEYWORDS: Interstitial cystitis; Potassium sensitivity test; Cystometry; Urinary urgency; Nocturia; Painful bladder syndrome

CORRESPONDENCE: Arlon Breno da Silveira, Rua Amélia, 610. Recife/PE. CEP – 52011-050 Brazil ().

CITATION: Urotoday Int J. 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.08



A Case of Penile Trauma Caused by Magnets


The authors report a case of pediatric penile trauma that was caused by a magnet. No similar case has been recorded. The injury was self-inflicted, caused by 2 pieces of magnet placed on opposing sides of the penile shaft. This resulted in 2 circular scars extending to, but not through, Buck's fascia. An operative procedure to remove the 2 magnets was required. Long-term follow up showed no serious complications.

KEYWORDS: Penis; Penile trauma; Magnet

CORRESPONDENCE: Dr. Ahmed Al-Sameraaii, Department of Urology, The St. George Hospital, Gray Street, Kogarah 2217, NSW, Australia ().

CITATION: UroToday Int J 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.10



A Four-Gene Expression Signature for Prostate Cancer Cells Consisting of UAP1, PDLIM5, IMPDH2, and HSPD1


INTRODUCTION:The objective of the study was to develop a gene expression test that is highly associated with the presence of prostate cancer for use as an adjunct to the pathology examination of tissue.

METHODS: A gene expression database (U133A Affymetrix) was produced from 87 preparations of laser microdissected cells obtained from cancer (G3 and G4) and noncancer prostate tissues. The database was analyzed using univariate feature ranking and recursive feature elimination algorithms (support vector machine) to identify overexpressed genes that were associated with prostate cancer. RT-PCR assays were developed for the unique 4-gene set that was found to be reflective of prostate cancer. The gene expression data were used to construct a mathematical equation to classify tissues as cancer vs noncancer. The RT-PCR tests and the calculated gene expression score were validated in an independently collected set of formalin-fixed and fresh-frozen prostate tissues.

RESULTS: Analysis of the U133A gene expression database identified a group of 63 genes that were overexpressed in cancer and also gave an AUC (area under the curve) of > 0.84 for separating cancer vs noncancer. The gene discovery was validated with a database of 164 independently collected tissues reported in the Oncomine database. The 63 gene set was reduced to a subset of 4 complementary genes (UAP1, PDLIM5, IMPDH2, and HSPD1), using univariate feature ranking and recursive feature elimination (RFE) algorithms that gave an AUC = 0.94 for discrimination between cancer and noncancer prostate cells. Quantitative RT-PCR (reverse transcriptase polymerase chain reaction) assays were developed and validated. A mathematical formula based on the gene expression values of the 4 genes along with a housekeeping gene was developed for the classification of cancer vs noncancer tissues. In a blinded validation study of 71 independent prostate tissue samples that included both fresh prostate tissues and formalin fixed tissues, the 4-gene test gave a sensitivity of 90% with a specificity of 97% (the 95% confidence interval was 86% - 100%).

CONCLUSION: The 4-gene RT-PCR test can be used to detect Gleason grade 3 and grade 4 cancer cells in prostate tissue and may be useful as an adjunct test to the pathology examination of prostate tissue taken at biopsy or prostatectomy.

KEYWORDS: Prostate cancer detection; Support vector machine; Gene signature; UAP1, PDLIM5, IMPDH2, HSPD1, DNA microarray; RT-PCR assay

CORRESPONDENCE: Herbert A. Fritsche, PhD, Dept. Laboratory Medicine, MD Anderson Cancer Center, Houston, TX 77030 ().

CITATION: Urotoday Int J. 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.06



Seminal Improvement Following Microsurgical Subinguinal Varicocelectomy: Preoperative Sonographic Parameters of Success


INTRODUCTION: The aims of the study were to: (1) evaluate the use of color Doppler ultrasound to diagnose and grade varicocele, and (2) identify the ultrasonographic patient selection criteria for microsurgical subinguinal varicocelectomy that would result in the best seminal improvement.

METHODS: Participants were 94 infertile patients undergoing microsurgical subinguinal varicocelectomy. All patients were evaluated with a case history, physical examination, semen analysis, hormonal assay, and color Doppler scrotal ultrasound. Postoperative improvement indexes in sperm concentration, sperm motility and normal sperm morphology were calculated. Improvement index > 0.5 was considered a good outcome. Statistical analysis was done to show the relationship between microsurgical varicocelectomy outcome and testicular vein diameter at the lower testicular pole and the degree of reflux measured by color Doppler ultrasound.

RESULTS: Seminal improvement indexes > 0.5 were found for sperm concentration, motility, and morphology in 61.3%, 29.9% and 19.3% of cases, respectively. Patients with testicular vein diameter ≥ 2.5 mm at the lower pole of the testis had a significantly higher seminal improvement index in sperm concentration, motility, and morphology than those with a testicular vein diameter < 2.5 mm (P = .001, .001, .003, respectively). Patients with reflux detected by color Doppler ultrasound at the lower pole of the testis had a significantly higher seminal improvement index in sperm concentration, motility, and morphology than patients with reflux only in the supratesticular venous channels (P = .02, .013, .042, respectively).

CONCLUSION: Color Doppler ultrasound is an important method for accurate diagnosis and grading of varicocele and for prediction of the outcome of varicocelectomy. Microsurgical subinguinal varicocelectomy is recommended for patients with testicular vein diameter ≥ 2.5 mm, regardless of the grade of reflux at the inferior pole of the testis.

KEYWORDS: Color Doppler ultrasound; Varicocele; Microsurgical varicocelectomy; Seminal improvement.

CORRESPONDENCE: Hashem Hafez, M.D., Department of Urology, Faculty of Medicine, Suez Canal University, Ring Road, Ismailia 41115, Egypt ()

CITATION: UroToday Int J 2009 Aug;2(4). doi:10.3834/uij.1944-5784.2009.08.04.