Firouz Daneshgari

Complications of Mid Urethral Slings: Important Outcomes for Future Clinical Trials

PURPOSE Mid urethral slings are becoming the first line surgical treatment for stress urinary incontinence in women. We reviewed the complications of mid urethral sling placement and their potential pathophysiology. MATERIALS AND METHODS We conducted a literature search on MEDLINE from 1995 to 2007 using the key words sling, complications, mid-urethral slings, transvaginal tape, transobturator tape, trials, pathophysiology and complications. The Cochrane database was also searched. The results were summarized according to the type of mid urethral slings reported. RESULTS There were 928 MEDLINE citations for sling and complications, 279 for sling and complications and bladder, and 68 for sling and complications and voiding dysfunction. The reported complication rates ranged from 4.3% to 75.1% for retropubic and 10.5% to 31.3% for transobturator mid urethral slings. Complications included bladder perforation, hemorrhage, bowel injury, vaginal extrusion, de novo urgency and urge incontinence, urinary tract infections and voiding dysfunction. Retropubic mid urethral slings led to a higher occurrence of complications such as bladder perforation and hematoma. In addition, the retropubic approach resulted in serious complications such as bowel injury, major vascular injury and death. Groin pain was more common after the transobturator approach. Experimental studies indicated that the potential mechanisms for sling complications may include vaginal dissection, denervation injury and bladder remodeling. CONCLUSIONS Mid urethral slings result in bothersome complications which should not be minimized. Awareness of these complications should encourage improvements in patient counseling as well as further investigation of the underlying mechanisms. Decreasing complications should be considered an important outcome for future clinical studies of mid urethral slings.

Diabetic Bladder Dysfunction: Current Translational Knowledge

PURPOSE Diabetes mellitus, a metabolic disorder caused by an absolute or relative deficiency of insulin, is a debilitating and costly disease with multiple serious complications. Lower urinary tract complications are among the most common complications of diabetes mellitus. The most common, bothersome lower urinary tract complication of diabetes mellitus is diabetic cystopathy or diabetic bladder dysfunction. We reviewed the current translational knowledge of diabetic bladder dysfunction. MATERIALS AND METHODS We performed a search of the English literature through PubMed. The key words used were diabetes and bladder dysfunction or cystopathy. Our data and perspective are provided for consideration of the future direction of research. RESULTS Despite traditional recognition of diabetic bladder dysfunction as a voiding problem characterized by poor emptying and overflow incontinence, recent clinical and experimental evidence indicate storage problems such as urgency and urge incontinence in diabetes mellitus cases. Recent experimental evidence from studies of diabetic bladder dysfunction in small animal models of diabetes mellitus show a temporal effect on diabetic bladder dysfunction. Early phase diabetes mellitus causes compensated bladder function and the late phase causes decompensated bladder function. The temporal theory could plausibly provide the scientific road map to correlate clinical and experimental findings, and identify the role of mechanisms such as polyuria, hyperglycemia, oxidative stress, autonomic neuropathy and decompensation of the bladder contractile apparatus in the creation of clinical and experimental manifestations of diabetic bladder dysfunction. CONCLUSIONS Diabetic bladder dysfunction includes time dependent manifestations of storage and emptying problems. Identifying mechanistic pathways would lead to the identification of therapeutic intervention.

Robotic abdominal sacrocolpopexy/sacrouteropexy repair of advanced female pelvic organ prolaspe (POP): utilizing POP‐quantification‐based staging and outcomes

Associate Editor

Animal Models of Female Stress Urinary Incontinence

PURPOSE Urinary incontinence affects 40% of women in the United States and stress urinary incontinence accounts for a large portion of affected patients. As defined by the International Continence Society, stress urinary incontinence is the involuntary leakage of urine upon effort, exertion, sneezing or coughing. Since the ultimate success of long-term management for any condition is based on an understanding of its pathophysiology, and because the pathophysiology of stress urinary incontinence is incompletely defined, animal models have recently been developed to better understand stress urinary incontinence and develop novel treatment alternatives. MATERIALS AND METHODS Several animal models for urethral dysfunction have emerged in the last few years, including those based on pathophysiological theories of urethral sphincter dysfunction that were designed to simulate maternal birth trauma. Other models have focused on the creation of a durable model of dysfunction for investigating novel treatments. RESULTS Since animals cannot express intent, these animal models have focused on measuring decreased urethral resistance. The most widely used methods are the sneeze test, the tilt table technique and the leak point pressure test. Newer techniques include abdominal leak point pressure, urethral pressure measurement and retrograde urethral perfusion pressure. In addition to the advantages and disadvantages of each technique, all methods measure the composite contribution to urethral resistance from smooth and striated muscle, urethral closure and connective tissue, although none measures intent. CONCLUSIONS We critically reviewed the different models of stress urinary incontinence and urethral dysfunction as well as the different methods of measuring urethral resistance.

COMPUTER MODELING OF PROSTATE BIOPSY: TUMOR SIZE AND LOCATION-NOT CLINICAL SIGNIFICANCE-DETERMINE CANCER DETECTION

PURPOSE Sampling error is an inherent problem of prostate biopsy, and the determination of clinical significance based on biopsy results is problematic. We quantify the dimensions of these problems by computer simulation. MATERIALS AND METHODS We constructed 3-dimensional solid computer models of 59 autopsy prostates containing clinically undetected prostate cancer, and performed simulations of the standard prostate biopsy method. RESULTS Biopsy simulation detected 19 tumors from the 59 prostates, the majority of which were in the most accessible portion of the prostate, the posterior peripheral zone. Using 0.5 cc or greater tumor volume or less than 0.5 cc and Gleason sum 7 or greater as criteria of significance, the model detected 58% (11 of 19) significant tumors and 20% (8 of 40) insignificant tumors. With 0.25 cc or greater tumor volume or less than 0.25 cc and Gleason sum 7 or greater as criteria 15 of 29 significant (52%) and 4 of 30 insignificant (13%) tumors were detected. Among significant tumors defined by either volume criterion there was a statistical difference between detected and undetected tumors in terms of mean tumor volume and mean ratio of tumor volume-to-prostate volume. Among insignificant tumors defined by either criterion there was no such difference. CONCLUSIONS As much as 20 to 40% of currently detected prostate cancer may be histologically insignificant, as 4 of 19 cancers were detected when 0.25 cc was used as volume determinant of clinical significance and 8 of 19 were detected when 0.5 cc volume was used. These tumors are detected randomly. On the other hand, perhaps only one-half to three-fourths of clinically significant prostate cancers are being detected, and then only because the volume and anatomic location make them hard to miss.

Endocrine therapy of advanced carcinoma of the prostate

Increasing evidence suggests that growth of the prostatic tissue is regulated by a network of hormones and growth factors, in which androgens play the prominent role. Hormonal manipulation remains the core of treatment for locally advanced and metastatic prostate cancer. Achievement of a complete androgen blockade, by surgical or medical means or a combination of both, offers superior results in palliative management of advanced disease. Management of hormonal refractory cancer, however, remains a challenge to clinicians.

Animal models and their use in understanding lower urinary tract dysfunction

This review will highlight appropriate animal models for the study of a number of disorders involving changes to lower urinary tract function. A major hurdle to the development of animal models for human lower urinary tract disorders is that the clinical pathophysiology of the latter mostly remain idiopathic. Acute injury/inflammation of otherwise healthy animals has often been used to study effects on a target tissue/organ. However, these “acute” models may not adequately address the characteristics of “chronic” visceral disorders. In addition, the relevance of observed changes following acute injury/inflammation, in terms of possible therapeutic targets, may not reflect that which occurs in the human condition. We have therefore emphasized the situations when animal models are required to investigate lower urinary tract disorders and what they should set out to achieve. In particular we have discussed the merits and disadvantages of a number of paradigms that set out to investigate specific lower urinary tract disorders or situations associated with these conditions. These include animal models of overactive bladder, stress urinary incontinence, ageing and congenital defects of the urinary tract and bladder pain syndrome. Neurourol. Urodynam. 29:603–608, 2010. Copyright

External Urethral Sphincter Activity in Diabetic Rats

To examine the temporal effects of diabetes on the bladder and the external urethral sphincter (EUS) activity in rats.

Lower urinary tract phenotype of experimental autoimmune cystitis in mouse: a potential animal model for interstitial cystitis.

To examine bladder function in a newly developed experimental autoimmune cystitis (EAC) model in female SWXJ strain mice, as a potential animal model for interstitial cystitis (IC).

Lower urogenital tract anatomical and functional phenotype in lysyl oxidase like-1 knockout mice resembles female pelvic floor dysfunction in humans

Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.