The Journal of Urology - Articles in Press

3-Dimensional Elastic Registration System of Prostate Biopsy Location by Real-Time 3-Dimensional Transrectal Ultrasound Guidance With Magnetic Resonance/Transrectal Ultrasound Image Fusion - Corrected Proof

2012-01-23

Purpose: We determined the accuracy of the novel Urostation 3-dimensional transrectal ultrasound system (Koelis, La Tranche, France) for image based mapping biopsies in a prostate phantom. The system is capable of 1) registering the 3-dimensional location of each biopsy track in the 3-dimensional prostate volume data and 2) performing elastic image fusion of transrectal ultrasound with magnetic resonance imaging. Materials and Methods: We used 3 CIRS-053 prostate phantoms containing 3 hypoechoic lesions to perform ultrasound guided biopsy and 3 CIRS-066 phantoms (Computerized Imaging Reference Systems, Norfolk, Virginia) containing 3 isoechoic but magnetic resonance imaging visible lesions to perform magnetic resonance fusion guided biopsy. Three targeted biopsies were done per lesion. Each biopsy tract was injected with gadolinium based magnetic resonance contrast mixed with india ink. Phantoms were then subjected to 1 mm slice magnetic resonance imaging and serial step sectioning to assess the accuracy of targeted biopsy. Results: A total of 27 ultrasound guided biopsies were targeted into 9 hypoechoic lesions. All 27 biopsies (100%) successfully hit the target lesion. For hypoechoic lesions mean ± SD procedural targeting error was 1.52 ± 0.78 mm and system registration error was 0.83 mm, resulting in an overall error of 2.35 mm. Of the 27 magnetic resonance fusion biopsies 24 (84%) hit the lesion. For isoechoic lesions mean procedural targeting error was 2.09 ± 1.28 mm, resulting in an overall error of 2.92 mm. Conclusions: The novel, computer assisted, 3-dimensional transrectal ultrasound biopsy localization system achieved encouraging accuracy with less than 3 mm error for targeting hypoechoic and isoechoic lesions. The ability to register actual biopsy trajectory and perform elastic magnetic resonance/ultrasound image fusion is a significant advantage for future focal therapy application.

Association of Randall Plaque With Collagen Fibers and Membrane Vesicles - Corrected Proof

Saeed R. Khan, Douglas E. Rodriguez, Laurie B. Gower, Manoj Monga — 2012-01-23

Purpose: Idiopathic calcium oxalate kidney stones develop by calcium oxalate crystal deposition on Randall plaque. The mechanisms involved in Randall plaque formation are still unclear. We hypothesized that Randall plaque formation is similar to that of vascular calcification, involving components of extracellular matrix, including membrane bound vesicles and collagen fibers. To verify our hypothesis we critically examined renal papillary tissue from patients with stones. Materials and Methods: We performed 4 mm cold cup biopsy of renal papillae on 15 patients with idiopathic stones undergoing percutaneous nephrolithotomy. Tissue was immediately fixed and processed for analysis by various light and electron microscopic techniques. Results: Spherulitic calcium phosphate crystals, the hallmark of Randall plaque, were seen in all samples examined, including in interstitium and laminated basement membrane of tubular epithelium. Large crystalline deposits were composed of dark elongated strands mixed with spherulites. Strands showed banded patterns similar to collagen. Crystal deposits were surrounded by collagen fibers and membrane bound vesicles. Energy dispersive x-ray microanalysis and electron diffraction identified the crystals as hydroxyapatite. Few kidneys were examined and urinary data were not available on all patients. Conclusions: Results showed that crystals in Randall plaque are associated with collagen and membrane bound vesicles. Collagen fibers appeared calcified and vesicles contained crystals. Crystal deposition in renal papillae may have started with membrane vesicle induced nucleation and grown by the further addition of crystals at the periphery in a collagen framework.

A Novel Therapeutic Vaccine of Mouse GM-CSF Surface Modified MB49 Cells Against Metastatic Bladder Cancer - Corrected Proof

2012-01-23

Purpose: Immunotherapy is considered effective for muscle invasive bladder cancer mini metastasis. We developed what is to our knowledge a novel technology by which streptavidin tagged mouse GM-CSF was displayed on the surface of biotinylated bladder cancer cells to induce antitumor immunity. Materials and Methods: Mouse subcutaneous and lung metastasis bladder cancer models were established. Mice were injected subcutaneously with 1 × 106 mouse GM-CSF surface modified MB49 bladder cancer cells and monitored for tumor growth and survival. Immunohistochemical and flow cytometric assay were done to assess the proportion of T lymphocytes. The T-lymphocyte cytotoxicity assay was performed to assess MB49 specific cytotoxicity. On day 60 after MB49 implantation the vaccine cured mice were injected subcutaneously with MB49 or RM-1 cells in the left or right hind leg, respectively. They were monitored for survival and T-lymphocyte cytotoxicity. Results: Mouse GM-CSF surface modified vaccine significantly inhibited tumor growth in the subcutaneous model and extended survival in the lung model. More CD4 and CD8 T cells appeared at tumor sites and in peripheral blood in the vaccine treated group than in other control groups. Splenocytes from the vaccine treated group showed the most potent cytotoxicity on MB49 cells. Cured mice in the vaccine treated group resisted the second injection of MB49 bladder cancer cells but not the RM-1 prostate cancer cell challenge. Conclusions: Mouse GM-CSF surface modified MB49 bladder cancer cell vaccine induced specific antitumor immunity and was efficient for metastatic bladder cancer.

Composite Urinary Reservoir in Dogs: Histological Findings - Corrected Proof

2012-01-23

Purpose: This animal study was designed to investigate whether the composite urinary reservoir might lessen the premalignant histological alterations observed after bladder augmentation performed with a gastric segment or large bowel. Materials and Methods: Composite urinary reservoirs were created using gastric and colonic segments simultaneously in 8, 3-month-old female beagle dogs by augmenting half the native bladder. Two dogs with gastrocystoplasty and 2 with colocystoplasty served as controls. Biopsies were taken from the native bladder, and the gastric and colonic segments at augmentation, and endoscopically 4 and 8 months postoperatively. The dogs were sacrificed and open biopsied 12 months postoperatively. Tissue specimens were examined with routine hematoxylin and eosin, reaction and immunohistological staining for PCNA. Results: At the creation of composite reservoir and gastrocoloplasty or colocystoplasty all specimens showed normal histology. At 12 months postoperatively dysplasia was found in 1 gastric segment, 2 native bladders and 3 colonic segments in the composite reservoir group. There was a single carcinoma in situ in 1 gastric segment in the composite reservoir group. In the control groups 1 colonic segment and 1 native bladder dysplasia were detected at the end of 12-month followup. There was an in situ carcinoma in 1 gastric segment in the composite reservoir. Conclusions: A composite reservoir did not decrease premalignant changes in dogs during 12 months of followup. Laboratory investigations, molecular studies and longer followup are needed to approach the question of early malignant alterations after augmentation cystoplasty in animals and patients.

Effect of Chemical Stimulation of the Medial Frontal Lobe on the Micturition Reflex in Rats - Corrected Proof

2012-01-23

Purpose: We assessed the influence of the medial frontal lobe on micturition after chemical stimulation. We also examined the relation between the medial frontal lobe and the rostral pontine reticular formation, which has a strong inhibitory effect on micturition. Materials and Methods: A total of 35 female rats underwent continuous cystometry. Bladder activity changes were examined after physiological saline, glutamate, the glutamate receptor antagonist MK-801, noradrenaline or the adrenergic α-1 receptor antagonist naftopidil was injected in the medial frontal lobe. When glutamate was injected in the medial frontal lobe, MK-801 was also injected in the rostral pontine reticular formation. Results: Glutamate injection in the medial frontal lobe prolonged the interval between bladder contractions while injection of the glutamate antagonist MK-801 shortened the interval. Glutamate injection in the medial frontal lobe just after MK-801 injection in the ipsilateral rostral pontine reticular formation also prolonged the interval between bladder contractions. However, after prior injection of MK-801 in the bilateral rostral pontine reticular formation glutamate injection in the medial frontal lobe did not influence cystometric parameters. Noradrenaline injection in the medial frontal lobe shortened the interval between bladder contractions while injection of its antagonist naftopidil prolonged the interval. Conclusions: Medial frontal lobe neurons excited by glutamate inhibited the micturition reflex via activation of the rostral pontine reticular formation by glutamatergic projection while medial frontal lobe neurons excited by noradrenaline facilitated the micturition reflex. Thus, the medial frontal lobe may be an important integration center for the initiation of micturition and urine storage mechanisms.

Effects of Pseudomonas Aeruginosa Virulence Factor Pyocyanin on Human Urothelial Cell Function and Viability - Corrected Proof

2012-01-23

Purpose: We determined the effects of Pseudomonas aeruginosa virulence factor pyocyanin on human urothelial cell viability and function in vitro. Materials and Methods: RT4 urothelial cells were treated with pyocyanin (1 to 100 μM) for 24 hours. After exposure the treatment effects were measured according to certain end points, including changes in urothelial cell viability, reactive oxygen species formation, caspase-3 activity, basal and stimulated adenosine triphosphate release, SA-β-gal activity and detection of acidic vesicular organelles. Results: The 24-hour pyocyanin treatment resulted in a concentration dependent decrease in cell viability at concentrations of 25 μM or greater, and increases in reactive oxygen species formation and caspase-3 activity at 25 μM or greater. Basal adenosine triphosphate release was significantly decreased at all tested pyocyanin concentrations while stimulated adenosine triphosphate release was significantly inhibited at pyocyanin concentrations of 12.5 μM or greater with no significant stimulated release at 100 μM. Pyocyanin treated RT4 cells showed morphological characteristics associated with cellular senescence, including SA-β-gal expression. This effect was not evident at 100 μM pyocyanin and may have been due to apoptotic cell death, as indicated by increased caspase-3 activity. An increase in acridine orange stained vesicular-like organelles was observed in RT4 urothelial cells after pyocyanin treatment. Conclusions: Exposure to pyocyanin alters urothelial cell viability, reactive oxygen species production and caspase-3 activity. Treatment also results in cellular senescence, which may affect the ability of urothelium to repair during infection. The virulence factor depressed stimulated adenosine triphosphate release, which to our knowledge is a novel finding with implications for awareness of bladder filling in patients with P. aeruginosa urinary tract infection.

Effect of OnabotulinumtoxinA on Intramural Parasympathetic Ganglia: An Experimental Study in the Guinea Pig Bladder - Corrected Proof

Ana Coelho, Francisco Cruz, Célia D. Cruz, António Avelino — 2012-01-23

Purpose: We investigated whether onabotulinumtoxinA injected in the bladder would affect preganglionic parasympathetic nerve endings in intramural ganglia. Materials and Methods: Guinea pig bladders were injected with 5 U of botulinum toxin. At 24 hours bladders were collected and processed for immunohistochemistry using tyrosine hydroxylase, and intact and cleaved SNAP-25. To identify the different populations of affected fibers coursing the ganglia we performed double immunoreactions for cleaved SNAP-25 and VAChT, TH or CGRP. Results: VAChT immunoreactive fibers were identified in axons and varicosities of presynaptic to postganglionic parasympathetic neurons. Those fibers were also immunoreactive to SV2 and SNAP-25. The rare CGRP and TH immunoreactive fibers coursing in the ganglia did not express SV2 or SNAP-25. After onabotulinumtoxinA injection the cleaved form of SNAP-25 was abundantly expressed in parasympathetic fibers. Conclusions: Botulinum toxin injection in the bladder wall affects preganglionic parasympathetic nerve terminals. This could contribute to the strong effect of botulinum toxin on bladder smooth muscle activity.

Introducing a Large Animal Model to Create Urethral Stricture Similar to Human Stricture Disease: A Comparative Experimental Microscopic Study - Corrected Proof

2012-01-23

Purpose: In this tissue engineering study we investigated urethral stricture formation to evaluate different treatment modalities in the large animal model and validate the most current, comparable effect of human stricture development for successful human clinical application. Materials and Methods: In 12 male minipigs stricture formation was evaluated by urethrography 1, 8 and 12 weeks after stricture induction by ligation, urethrotomy or thermocoagulation. Normal human urethral and scar tissue of 6 patients was harvested and compared to animal specimens. The effect of urethral damage was investigated for microvessel density and collagen I:III ratio. Results: A week after urethrotomy urothelium covered the spongiosum tissue, showing minimal infiltration of lymphocytes and macrophages, and sporadic eosinophil granulocytes. However, increased connective tissue was observed with time as well as urethral luminal narrowing, vascular network loss (decreased microvessel density) and significantly increased collagen with a favorably revised collagen type I:III ratio. The 3 methods of stricture induction resulted in different stricture severity in the animal model (thermocoagulation >ligation >urethrotomy). Porcine urethral samples after thermocoagulation showed a significantly increased collagen I:III ratio (p <0.001), almost equal to that of human urethral stricture specimens. Conclusions: We successfully developed a large animal model in which to study urethral stricture formation by defined iatrogenic intervention. The established animal model advances investigation to evaluate new therapy modalities in a preclinical setting to treat urethral stricture and predict clinical outcome.

A Brief History of Rejuvenation Operations - Corrected Proof

Michael A. Kozminski, David A. Bloom — 2012-01-23

Purpose: We discuss the place in history of operative procedures for hormonal rejuvenation. Materials and Methods: The scientific and historical literature was reviewed. Results: In the early 20th century, building on the earlier work of Berthold and Brown-Séquard, Eugen Steinach developed a combination of vasectomy and vasoligature that became known as the Steinach operation. This procedure, along with testicular implantation popularized by Serge Voronoff, was an attempt to rejuvenate older and fatigued men around the world. The early experiments and results of Steinach, Voronoff and their followers were plagued by secrecy, subjectivity and sensationalism in an effort to produce the most scientific data. These rejuvenists used their results to outcompete one another. Ultimately the lack of verifiable outcome data and the chemical isolation of the “internal secretion” (testosterone) ended this era in surgery. Conclusions: Always a work in progress, the practice of medicine has been guided by human curiosity with trial, error and success. History records aberrant paths along the way and the rejuvenation movement was one such journey. While superseded by later knowledge, the efforts of the rejuvenists comprise an interesting chapter in the development of urology, endocrinology and transplant surgery.

Re: Hydrodissection of Neurovascular Bundles During Open Radical Prostatectomy Improves Postoperative Potency: M. I. Patel, D. Spernat and E. Lopez-CoronaJ Urol 2011; 186: 233–237 - Corrected Proof

Marizio Bellina, Mauro Mari, Alessandra Ambu, Francesco Mangione — 2012-01-23

The authors describe the use of a hydrodissection technique during radical retropubic prostatectomy to minimize surgical damage to neurovascular bundles and to obtain better restoration of postoperative potency. In this regard, we already presented our preliminary results with a hydrodissection technique for neurovascular bundle preservation during retropubic radical prostatectomy in 35 selected patients studied between January 2006 and March 2007. In our experience hydrodissection (especially when performed with loupe magnification) permits better recognition of the prostatic fascia and the thin “Aphrodite veil,” and improves neurovascular bundle preservation with minimal bleeding. In carefully selected patients we also performed radical retropubic prostatectomy with seminal vesicle preservation, obtaining further improvement of functional results without increasing oncologic risk. Further randomized studies are needed to investigate whether hydrodissection, even if anatomically intriguing, is really useful compared to the nerve sparing technique previously described by Walsh.

Re: Familial Testicular Torsion: J. Cubillos, J. S. Palmer, S. C. Friedman, J. Freyle, F. C. Lowe and L. S. PalmerJ Urol, suppl, 2011; 185: 2469–2472 - Corrected Proof

Alex Shteynshlyuger — 2012-01-23

The authors make an important contribution to the literature with a prospective study of the prevalence of familial testicular torsion among all patients with testicular torsion. The article certainly is an eye-opener.

Attenuation of Spermatogonial Stem Cell Activity in Cryptorchid Testes - Corrected Proof

2012-01-23

Purpose: To elucidate the mechanism of infertility caused by cryptorchidism we focused on early stage spermatogenesis and spermatogonial stem cell activity in undifferentiated spermatogonia in cryptorchid testes. Materials and Methods: Histological findings and expression patterns of the stem cell marker undifferentiated embryonic cell transcription factor 1 were examined in a unilateral cryptorchid rat model. We removed unilateral descended testis and contralateral descended testis from cryptorchid and normal rats (control), respectively, 18 days postcoitum to 144 days postpartum. Results: In descended testes gonocyte differentiation into early A spermatogonia occurred at 9 days postpartum. However, this transformation was altered in undescended testes. Furthermore, the undifferentiated embryonic cell transcription factor 1 negative early A spermatogonia-to-positive early A spermatogonia ratio was significantly higher in the undescended testis group (mean ± SD 0.69 ± 0.04) than in the control (0.46 ± 0.10, p = 0.037) and descended testis (0.44 ± 0.05, p = 0.022) groups, indicating decreased early A spermatogonia with spermatogonial stem cell activity in cryptorchid testes. Conclusions: In cryptorchid testes the differentiation from gonocytes into early A spermatogonia and the stem cell activity of early A spermatogonia were altered during the early stage of spermatogenesis, suggesting that the loss of spermatogonial stem cell activity in cryptorchid rats resulted in altered spermatogenesis, thus interfering with fertility.

Re: Epigenetic Regulation of Phosphatidylinositol 3,4,5-Triphosphate-Dependent Rac Exchanger 1 Gene Expression in Prostate Cancer Cells - Corrected Proof

Anthony Atala — 2012-01-23

C. Y. Wong, H. Wuriyanghan, Y. Xie, M. F. Lin, P. W. Abel and Y. Tu Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska

Re: Targeting the Regulation of Androgen Receptor Signaling by the Heat Shock Protein 90 Cochaperone FKBP52 in Prostate Cancer Cells - Corrected Proof

Anthony Atala — 2012-01-23

J. T. De Leon, A. Iwai, C. Feau, Y. Garcia, H. A. Balsiger, C. L. Storer, R. M. Suro, K. M. Garza, S. Lee, Y. S. Kim, Y. Chen, Y. M. Ning, D. L. Riggs, R. J. Fletterick, R. K. Guy, J. B. Trepel, L. M. Neckers and M. B. Cox

Re: IGFBP-3 is a Metastasis Suppression Gene in Prostate Cancer - Corrected Proof

Anthony Atala — 2012-01-23

H. H. Mehta, Q. Gao, C. Galet, V. Paharkova, J. Wan, J. Said, J. J. Sohn, G. Lawson, P. Cohen, L. J. Cobb and K. W. Lee Mattel Children's Hospital UCLA, Los Angeles, California

Re: Modified Hospital Elder Life Program: Effects on Abdominal Surgery Patients - Corrected Proof

Richard K. Babayan — 2012-01-23

C. C.-H. Chen, M.-T. Lin, Y.-W. Tien, C.-J. Yen, G.-H. Huang and S. K. Inouye Department of Nursing, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan

Re: Laparoendoscopic Single-Site (LESS) Surgery Versus Conventional Laparoscopic Surgery: Comparison of Surgical Port Performance in a Surgical Simulator With Novices - Corrected Proof

Jeffrey A. Cadeddu — 2012-01-23

B. Brown-Clerk, A. E. de Laveaga, C. A. LaGrange, L. M. Wirth, B. R. Lowndes and M. S. Hallbeck Department of Industrial and Management Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska

Re: A Randomized Prospective Study of Single-Port and Four-Port Approaches for Hysterectomy in Terms of Postoperative Pain - Corrected Proof

Jeffrey A. Cadeddu — 2012-01-23

Y. W. Jung, M. Lee, G. W. Yim, S. H. Lee, J. H. Paek, H. Y. Kwon, E. J. Nam, S. W. Kim and Y. T. Kim Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Korea

Re: What Can We Learn From Pediatric Urology Certification Logs? - Corrected Proof

Douglas A. Canning — 2012-01-23

B. A. Kogan and P. J. Feustel Division of Urology, Department of Surgery, Albany Medical College, Albany, New York

Re: Evaluation of the United States Pediatric Urology Workforce and Fellowships: A Series of Surveys Performed in 2006–2010 - Corrected Proof

Douglas A. Canning — 2012-01-23

D. A. Husmann, J. C. Routh, J. A. Hagerty, G. M. Cannon, P. Gomez, E. Y. Cheng and S. Skoog Department of Urology, Mayo Clinic, Rochester, Minnesota

Re: Does Better Quality of Care for Falls and Urinary Incontinence Result in Better Participant-Reported Outcomes? - Corrected Proof

Tomas L. Griebling — 2012-01-23

L. C. Min, D. B. Reuben, J. Adams, P. G. Shekelle, D. A. Ganz, C. P. Roth and N. S. Wenger Division of Geriatrics, University of Michigan Medical School, Ann Arbor, Michigan

Re: Prevalence and Effect on Health-Related Quality of Life of Overactive Bladder in Older Americans: Results From the Epidemiology of Lower Urinary Tract Symptoms Study - Corrected Proof

Tomas L. Griebling — 2012-01-23

C. C. Sexton, K. S. Coyne, C. Thompson, T. Bavendam, C. I. Chen and A. Markland Center for Health Outcomes Research, United BioSource Corp., Bethesda, Maryland

Re: Comparison of a New Length Measurement Technique for Inflatable Penile Prosthesis Implantation to Standard Techniques: Outcomes and Patient Satisfaction - Corrected Proof

Allen F. Morey — 2012-01-23

G. Henry, L. Houghton, D. Culkin, J. Otheguy, R. Shabsigh and D. A. Ohl Department of Urology, Regional Urology, Shreveport, Louisiana

Re: Penile Fracture: Long-Term Results of Surgical and Conservative Management - Corrected Proof

Allen F. Morey — 2012-01-23

W. M. Gamal, M. M. Osman, A. Hammady, M. Z. Aldahshoury, M. M. Hussein and M. Saleem Department of Urology, Sohag University, Sohag, Egypt

Re: Major Depression Drives Severity of American Urological Association Symptom Index - Corrected Proof

Steven A. Kaplan — 2012-01-23

T. V. Johnson, A. Abbasi, S. S. Ehrlich, R. S. Kleris, S. L. Chirumamilla, E. D. Schoenberg, A. Owen-Smith, C. L. Raison and V. A. Master Department of Urology, Emory University School of Medicine, Atlanta, Georgia

Re: Nocturic Episodes in Patients With Benign Prostatic Enlargement May Suggest the Presence of Obstructive Sleep Apnea - Corrected Proof

Steven A. Kaplan — 2012-01-23

H. Tandeter, S. Gendler, J. Dreiher and A. Tarasiuk Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Re: Increased Risk of Benign Prostatic Enlargement Among Patients With Liver Cirrhosis: A Nationwide Population-Based Study - Corrected Proof

Steven A. Kaplan — 2012-01-23

S. D. Chung and H. C. Lin Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, Ban Ciao and Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

Re: In Vitro Propagation of Human Prepubertal Spermatogonial Stem Cells - Corrected Proof