Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review.

Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation.

Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome.

47, XXY or Klinefelter syndrome (KS), the most common chromosomal aberration in males, is characterized by either absolute or relative hypogonadism with frequent decline in serum testosterone (T) following the onset of puberty. Decreased T levels are the result of testicular dysfunction with decrease in size of Leydig cells, and loss of germs and Sertoli cells leading to tubular hyalinization. Increase in estradiol results from over-expression of aromatase CYP19. Deficient androgen production and observed varied response of end-organs to T leads to delayed progression of puberty with decreased facial/body hair, poor muscle development, osteoporosis, and gynecomastia. It is possible that hypogonadism and excessive estradiol production contribute to emotional and social immaturity, and specific learning disabilities in KS. Based on the authors' experience and literature review, early fertility preservation and hormonal supplementation may normalize pubertal development, prevent metabolic sequelae of hypogonadism, and have a positive effect on academic and social development. No randomized clinical trials are available studying the effects of T supplementation on reproductive or cognitive issues in KS. Aggressive T supplementation (topical gel) and selective use of aromatase inhibitors may be considered at the onset of puberty with careful follow-up and titration to reach age-specific high-normal physiologic serum values. The decision to institute hormonal therapy should be part of a multidisciplinary approach including physical, speech, behavioral, and occupational therapy. © 2013 Wiley Periodicals, Inc.

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer.

BACKGROUND: Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2-T4aN0-N2M0 bladder cancer. METHODS: In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum-based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin-based chemotherapy compared with carboplatin-based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin-based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01-112.2). CONCLUSION: In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum-based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin- or carboplatin-based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy.

Predictive value of microtubule associated proteins tau and stathmin in patients with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane therapy.

PURPOSE: After encouraging results from 2 clinical trials performed at our institution to test intravesical taxane based chemotherapy for bacillus Calmette-Guérin refractory, nonmuscle invasive bladder cancer we designed a study to identify molecular markers linked to the optimal response to such treatment modality. MATERIALS AND METHODS: Included in the institutional review board approved study were 32 patients with nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer who received intravesical taxane chemotherapy, that is docetaxel or nanoparticle albumin-bound paclitaxel. Immunophenotype analysis on tissue samples obtained before intravesical taxane therapy was done using a panel of molecular markers, including Ki-67, p53, and the microtubule associated proteins tau and stathmin. RESULTS: Increased total tau (cytoplasmic and nuclear) and stathmin expression before intravesical taxane therapy was significantly associated with decreased recurrence-free survival (p <0.0001 and 0.007, respectively). A tau positive phenotype was an independent prognostic factor for recurrence-free survival on multivariate analysis (HR 15.66, 95% CI 2.68-91.71, p = 0.002). Neither the proliferation index assessed by Ki-67 expression nor p53 status was significantly associated with recurrence-free survival. CONCLUSIONS: Assessment of tau and stathmin protein expression should be considered to select patients before intravesical taxane based chemotherapy for nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer since those who have tumors with low tau/stathmin protein expression show a better response to therapy.

Antibiotic patterns with inflatable penile prosthesis insertion.

INTRODUCTION: A clear set of guidelines has not been defined in the use of antibiotics in penile prosthesis implantation. Aim. We surveyed urologists throughout the United States to determine current practice patterns regarding antibiotic use in primary and revision penile prosthesis surgery. METHODS: Fifty-two Sexual Medicine Society of North America (SMS) member urologist and 164 non-SMS member urologist responses were obtained. MAIN OUTCOME MEASURES: The survey contained 10 questions regarding antibiotic selection for primary and revision inflatable penile prosthesis (IPP) implantation. RESULTS: One hundred percent of responders in both groups utilize intraoperative antibiotics, most commonly vancomycin and gentamicin in both groups. Of SMS members, 94% prescribed postoperative home oral antibiotics in contrast to 88% of non-SMS members (P = 0.3). Among SMS members, the most common antibiotic prescribed postoperatively was levofloxacin 500 mg daily while among non-SMS members, the most common antibiotic postoperatively was cephalexin 500 mg 2-4 times daily. Of SMS members, antibiotic irrigation intraoperatively occurred with 100% and with 92% of non-SMS members (P = 0.04). Thirty-seven percent SMS physicians and 15% non-SMS physicians made modifications of intraoperative and postoperative antibiotics for high-risk patients (P = 0.001). In the circumstance of revision of a clinically noninfected IPP, 23% SMS and 16% non-SMS member physicians utilized additional antibiotics/treatment (P = 0.3). Sixteen of those surveyed admitted that they had been approached by their institution about their antibiotic use and asked to change. In the past 5 years, 29% surveyed have changed their practice patterns in antibiotic use. CONCLUSIONS: There is significant difference between practice patterns of SMS and non-SMS urologists in terms of antibiotic irrigation usage, modifications for high-risk patients, and consensus about the importance of antibiotic use with Coloplast Titan implant (Coloplast, Minneapolis, MN, USA). A significant lack of uniformity exists among urologists performing prosthetic surgery with regard to antibiotic protocols. A standard set of guidelines may prove useful to implanters.

Evaluation of preoperative bioimpedance spectroscopy quantification of body composition on predicting postoperative outcomes following robotic assisted radical prostatectomy (RARP).

INTRODUCTION: Bioimpedance spectroscopy (BIS) is a novel, precise quantification of body composition (BC) using low electrical currents through tissue. Accurate BC quantification may better predict postoperative outcomes. We compared BIS-BC and body mass index (BMI) for correlation with post-surgical outcomes in robotic assisted radical prostatectomy (RARP) patients. MATERIALS AND METHODS: Preoperative BIS-BC and BMI analyses were conducted on men with biopsy-proven prostate cancer undergoing RARP. Height, weight, percentage and fat mass (PFM, FM), percentage and fat-free mass (PFFM, FFM), percentage and total body water (PTBW, TBW), and percentage and intracellular/extracellular water (PICW, PECW, ICW, ECW) were obtained using the ImpediMed SFB7 Device (San Diego, CA, USA). Preoperative PSA, biopsy and pathologic Gleason scores, prostate volume, percentage tumor volume, margin status, operative time, estimated blood loss (EBL) and pathologic stage were recorded. Spearman's rank correlation was estimated to evaluate the association between BIS-BC results, BMI, and post-surgical outcomes. RESULTS: Between April 2009 and August 2010, 63 men had been enrolled in this ongoing study. Fourteen were of normal weight (18.5 kg/m2-24.9 kg/m2), 33 were overweight (25 kg/m2-29.9 kg/m2) and 16 were obese (BMI ≥ 30 kg/m2). Mean age was 60.7 years, mean preoperative PSA was 7.4 ng/mL, and median Gleason was 7. BMI correlated with FFM (p = 0.002), FM (p = 0.01), and PTBW (p = 0.02). FM correlated with preoperative PSA (p = 0.01). PFFM (p = 0.03), PFM (p = 0.03) and PTBW (p = 0.04) correlated with % tumor volume. ICW (p = 0.01) and TBW (p = 0.009) correlated with EBL. BMI (p = 0.04), PECW (p = 0.04), FM (p = 0.05), and PICW (p = 0.03) correlated with pathologic tumor stage. CONCLUSIONS: BMI correlates with BIS-BC FFM, FM and PTBW. PFFM, PFM and PTBW correlated with % tumor volume. ICW and TBW correlated with EBL. BMI, PECW, FM, and PICW correlated with pathologic tumor stage. BIS-BC metrics may be helpful in predicting post-RARP outcomes. Further study is required to validate these predictions.

Persistent motor deficits predict long-term bladder dysfunction in children following acute transverse myelitis.

PURPOSE: We determined whether motor and bladder recovery are correlated in children with acute transverse myelitis. MATERIALS AND METHODS: From 1995 to 2004, 14 children (8 males and 6 females) with acute transverse myelitis were retrospectively evaluated to determine if there was a correlation between motor and bladder recovery following disease onset. RESULTS: During the acute phase of the disease, all patients experienced lower extremity motor deficit and bladder dysfunction. Full motor recovery was associated with full bladder recovery, and no motor recovery was related to no bladder recovery. Partial motor recovery was associated with either no or partial bladder recovery. CONCLUSIONS: Motor and bladder recovery were related in our patients with transverse myelitis. Children with no motor recovery did not experience bladder recovery. No significant bladder recovery was seen beyond 4 months in our patients.

Prevention, identification, and management of post-operative penile implant complications of infection, hematoma, and device malfunction.

Penile prosthesis implant surgery is an effective management approach for a number of urological conditions, including medication refractory erectile dysfunction (ED). Complications encountered post-operatively include infection, bleeding/hematoma, and device malfunction. Since the 1970s, modifications to these devices have reduced complication rates through improvement in antisepsis and design using antibiotic coatings, kink-resistant tubing, lock-out valves to prevent autoinflation, and modified reservoir shapes. Device survival and complication rates have been investigated predominately by retrospective database-derived studies. This review article focuses on the identification and management of post-operative complications following penile prosthetic and implant surgery. Etiology for ED, surgical technique, and prosthesis type are variable among studies. The most common post-operative complications of infection, bleeding, and device malfunction may be minimized by adherence to consistent technique and standard protocol. Novel antibiotic coatings and standard antibiotic regimen may reduce infection rates. Meticulous hemostasis and intraoperative testing of devices may further reduce need for revision surgery. Additional prospective studies with consistent reporting of outcomes and comparison of surgical approach and prosthesis type in patients with variable ED etiology would be beneficial.

Possible germ cell-Sertoli cell interactions are critical for establishing appropriate expression levels for the Sertoli cell-specific MicroRNA, miR-202-5p, in human testis.

BACKGROUND: To examine human microRNA expression in fertile men and subsequently to compare expression patterns of miRNAs in fertile and infertile men, specifically men with Sertoli Cell Only (SCO) histopathology. METHODS: Testicular tissues from men with azoospermia and SCO, as well as those of men with normal spermatogenesis, were analyzed. MicroRNA was isolated using the miRCURY™ RNA Purification Kit. A miRCURY LNA™ Universal RT system was used for detection of microRNA by quantitative real-time PCR. MicroRNA localization was performed by in situ hybridizations (ISH) on formalin-fixed paraffin embedded (FFPE) tissue utilizing miRCURY LNA™ microRNA ISH technology. Statistical analysis was performed by GenEx V5.0. RESULTS: MicroRNA expression was determined for 13 normal fertile men and 5 men with the confirmed diagnosis of diffuse SCO. MiR-202-5p expression was reduced by 17-fold (P < 0.00001) in tissue from SCO men compared to normal. MiR-34c-5p was reduced by 346-fold (P < 0.00001), miR-10b was reduced 18-fold (P < 0.00001), miR-191 was reduced 20-fold (P = 0.001) and miR-126 was reduced 40-fold (P < 0.00001)) in tissues from SCO compared to normal fertile men. Using ISH, miR-202-5p was localized to Sertoli cells of men with normal spermatogenesis, but not in the Sertoli cells of men with SCO. CONCLUSION: Number of miRNAs are differentially expressed in normal fertile men compared to men with SCO. MicroRNA-202-5p is localized to Sertoli cells and its expression dramatically differs between fertile men and men whose germ cells are depleted, suggesting a novel interaction for regulating microRNA expression between the somatic and germ cell components of the seminiferous epithelium.

OBJECTIFS: Evaluer l'expression des microARN chez des hommes féconds puis comparer les profils d'expression de ces miRNAs chez des hommes féconds et des inféconds qui présentent plus particulièrement un syndrome de Sertoli seules (SCO) à l'histologie testiculaire. MATÉRIEL ET MÉTHODES: Ont été analysés des tissues testiculaires d'hommes avec azoospermie et SCO ainsi que ceux d'hommes avec spermatogenèse normale. Les miRNAs ont été isolés avec la trousse de Purification miRCURY™ RNA. Le système miRCURY LNA™ Universal RT a été utilisé pour la détection quantitative de miARNs par PCR en temps réel. La localisation des miARNs a été réalisée par hybridation in situ (HIS) sur des tissus fixés au formol et inclus en paraffine en utilisant la technologie miRCURY LNA™ microRNA ISH. Les analyses statistiques ont été faites avec GenEx V5.0. RÉSULTATS: L'expression des microARNs a été faite chez 13 hommes féconds et 5 hommes avec un diagnostic confirmé de SCO diffus. L'expression de miR-202-5p est réduite d'un facteur 17 (P < 0.00001) dans le tissu des hommes SCO par rapport au tissu des hommes à spermatogenèse normale. L'expression de miR-34c-5p est réduite d'un facteur 346 (P < 0.00001), celle de miR-10b d'un facteur 18 (P < 0.00001), celle de miR-191 d'un facteur 20 (P = 0.001) et celle de miR-126 d'un facteur 40 (P < 0.00001) dans les tissus des hommes SCO comparés à ceux des hommes à spermatogenèse normale. MiR-202-5p a été localisé par HIS dans les cellules de Sertoli des hommes à spermatogenèse normale, mais pas dans les cellules de Sertoli des hommes SCO. CONCLUSIONS: Nombre de miARNs sont exprimés différentiellement chez les hommes féconds par rapport aux hommes SCO. MicroARN-202-5p est localisé dans les cellules de Sertoli et son expression diffère de façon marquée entre les hommes féconds et ceux dont les cellules germinales sont absentes; ceci suggère une nouvelle interaction ­ entre les cellules somatiques et germinales constitutives de l'épithélium séminifère ­ impliquée dans la régulation de l'expression des microARNs.

Genetic evaluation of male infertility.

Men with severe oligospermia (<5 million sperm/mL ejaculate fluid) or azoospermia should receive genetic testing to clarify etiology of male infertility prior to treatment. Categorization by obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is critical since genetic testing differs for the former with normal testicular function, testicular volume (~20 mL), and follicle-stimulating hormone (FSH) (1-8 IU/mL) when compared to the latter with small, soft testes and increased FSH. History and physician examination along with laboratory testing (following appropriate genetic counseling) is critical to accurate selection of genetic testing appropriate for azoospermia due to primary testicular failure as compared with congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be warranted depending on the clinical context of severe oligospermia or NOA. The results of genetic testing guide management options. The most recent techniques for genetic analysis, including sperm microRNA (miRNA) and epigenetics, are forming the foundation for future genetic diagnosis and therapeutic targets in male infertility.

Obstructive azoospermia.

Obstructive azoospermia accounts for 40% of azoospermia and results from obstruction of the excurrent ducts (due to many causes) at any location between the rete testis and the ejaculatory ducts. The diagnosis of obstructive azoospermia (OA) requires a stepwise approach to differentiate it from nonobstructive OA and to formulate management options. Localization of the site of obstruction relies on history, physical examination, and possibly laboratory, genetic, imaging tests, and intraoperative findings. The prospects for patients with OA are excellent given recent advances in microsurgical approaches and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Successful outcomes are increasingly likely after microsurgical reconstruction techniques, permitting non-IVF pregnancies for many couples. When reconstruction is not an option, microsurgical sperm retrieval provides excellent outcomes for patients in conjunction with IVF and ICSI.

Bulbocavernosus muscle area measurement: a novel method to assess androgenic activity.

Serum testosterone does not correlate with androgen tissue activity, and it is critical to optimize tools to evaluate such activity in males. Ultrasound measurement of bulbocavernosus muscle (BCM) was used to assess the relationship between the number of CAG repeats (CAGn) in the androgen receptor (AR) and the BCM size; the changes in the number of CAGn over age were also evaluated. Transperineal ultrasound measurement of the BCM was also performed. AR CAGn were determined by high performance liquid chromatography, and morning hormone levels were determined using immunoassays. Forty-eight men had CAG repeat analysis. Twenty-five were <30 years of age, mean 23.7 years (s.d. = 3.24) and 23 were >45 years of age, mean 53 years (s.d. = 5.58). The median CAGn was 21 (13-29). BCM area was greater when the number of CAGn were <18 as compared to the number of CAGn >24 (P = 0.04). There was a linear correlation between the number of CAGn and the BCM area R 2 = 16% (P = 0.01). In the 45 to 65-years-old group, a much stronger negative correlation (R 2 = 29%, P = 0.01) was noticed. In the 19 to 29-years-old group, no such correlation was found (R 2 = 4%, P = 0.36). In older men, the number of CAGn increased with age (R 2 = 32%, P = 0.01). The number of CAGn in the AR correlates with the area of the BCM. Ultrasound assessment of the BCM is an effective surrogate to evaluate end-organ activity of androgens. The number of CAGn may increase with age.

Ubiquitin Specific Protease 26 (USP26) expression analysis in human testicular and extragonadal tissues indicates diverse action of USP26 in cell differentiation and tumorigenesis.

Ubiquitin specific protease 26 (USP26), a deubiquitinating enzyme, is highly expressed early during murine spermatogenesis, in round spermatids, and at the blood-testis barrier. USP26 has also been recognized as a regulator of androgen receptor (AR) hormone-induced action involved in spermatogenesis and steroid production in in vitro studies. Prior mutation screening of USP26 demonstrated an association with human male infertility and low testosterone production, but protein localization and expression in the human testis has not been characterized previously. USP26 expression analysis of mRNA and protein was completed using murine and human testis tissue and human tissue arrays. USP26 and AR mRNA levels in human testis were quantitated using multiplex qRT-PCR. Immunofluorescence colocalization studies were performed with formalin-fixed/paraffin-embedded and frozen tissues using primary and secondary antibodies to detect USP26 and AR protein expression. Human microarray dot blots were used to identify protein expression in extra-gonadal tissues. For the first time, expression of USP26 and colocalization of USP26 with androgen receptor in human testis has been confirmed predominantly in Leydig cell nuclei, with less in Leydig cell cytoplasm, spermatogonia, primary spermatocytes, round spermatids, and Sertoli cells. USP26 likely affects regulatory proteins of early spermatogenesis, including androgen receptor with additional activity in round spermatids. This X-linked gene is not testis-specific, with USP26 mRNA and protein expression identified in multiple other human organ tissues (benign and malignant) including androgen-dependent tissues such as breast (myoepithelial cells and secretory luminal cells) and thyroid tissue (follicular cells). USP26/AR expression and interaction in spermatogenesis and androgen-dependent cancer warrants additional study and may prove useful in diagnosis and management of male infertility.

When to ask male adolescents to provide semen sample for fertility preservation?

BACKGROUND: Fertility preservation in adolescents undergoing sterilizing radiation and/or chemotherapy is the standard of care in oncology. The opportunity for patients to provide a semen sample by ejaculation is a critical issue in adolescent fertility preservation. METHODS: Fifty males with no medical or sexual developmental abnormalities were evaluated. The subjects were screened for evidence of orgasmic, erectile, and ejaculatory dysfunction. A detailed sexual development history was obtained under an Institutional Review Board (IRB)-approved protocol. RESULTS: Fifty males, aged 18-65 years (mean 39±16.03 years) volunteered to be part of this study. The mean reported age for the onset of puberty was 12.39 years (95% CI, 11.99-12.80 years), 13.59 years (95% CI, 13.05-14.12 years) for the first ejaculation, 12.56 years (95% CI, 11.80-13.32 years) for the start of masturbation, and 17.26 years (95% CI, 16.18-18.33 years) for the first experienced intercourse. Seventy-five percent of the cohort reached puberty by the age of 13.33, experienced masturbation by 14.5, first ejaculated by the age of 14.83, and had intercourse at age of 19.15 years. The first experienced ejaculation fell 1.5 years after the onset of puberty in 80% present of the cohort, and 84% starts masturbation 1.5 years after the onset of puberty. The mean response between the younger and the older subject was not statistical significance. CONCLUSIONS: It is appropriate to consider a request for semen specimens by masturbation from teenagers at one year and six months after the onset of puberty; the onset age of puberty plus 1.5 years is an important predictor of ejaculation and sample collection for cryopreservation.

Relative efficacy of perioperative gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management of locally advanced urothelial carcinoma of the bladder.

OBJECTIVE: To compare the outcomes of patients treated in the perioperative setting with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) versus gemcitabine and cisplatin (GC). Systemic cisplatin-based chemotherapy regimens are the mainstay of treatment for patients with advanced bladder cancer. GC has often been used interchangeably with MVAC in neoadjuvant or adjuvant settings for patients with locally advanced (cT2N0M0-cT4N2M0) bladder cancer without adequate evidence. METHODS: A total of 114 patients treated with systemic chemotherapy for Stage T2-T4N0-N2M0 urothelial cell carcinoma of the bladder were included in the present study. The survival times were estimated and compared using the Kaplan-Meier method and log-rank test, respectively. Univariate and multivariate Cox proportional hazards models were used to determine the statistical significance. RESULTS: Of the 114 patients included in the present study, 37 (32%) were treated with GC and 77 (68%) with MVAC. In the neoadjuvant group, no difference was found between the 2 chemotherapeutic regimens in terms of the pathologic complete response rate at either cystectomy or during cystoscopy (14 [31%] of 45 MVAC patients vs 4 [25%] of 16 GC patients; P=.645). On multivariate analysis, the choice of regimen was not an independent predictor of cancer-specific death (hazard ratio 1.3, 95% confidence interval 0.67-2.57; P=.421) or overall survival (hazard ratio 1.3, 95% confidence interval 0.76-2.24; P=.330). CONCLUSION: Despite the lack of data on the relative efficacy of GC versus MVAC in the neoadjuvant and adjuvant settings, these regimens have been used interchangeably. The present investigation did not find the choice of cisplatin-based regimen to be an independent predictor of survival. A trend was seen toward improved survival and a greater complete response rate in the MVAC group.

Management of prostate cancer in HIV-positive patients.

Improved medical therapy for HIV-positive patients has helped delay the progression of HIV to AIDS and reduce AIDS deaths. This dramatically prolonged survival has resulted in increased detection of non-AIDS-defining malignancies, such as prostate cancer, in people with HIV. Reported prostate cancer incidences in HIV-positive men compared with the general population vary in different studies; however, its incidence in the general population has generally increased over time, owing to the widespread use of PSA testing and increased life expectancy. In the highly active antiretroviral therapy (HAART) era, evidence indicates that PSA kinetics and prostate cancer behavior are similar in HIV-positive and HIV-negative patients. Current American Urological Association (AUA) guidelines recommend screening of all men aged >or=40 years with a life expectancy >10 years, and HIV-positive patients should be included in this recommendation. Treatment options for HIV-positive patients with prostate cancer should include all those offered to the general population. Long-term treatment outcomes in HIV-positive patients remain uncertain; however, early results suggest response rates similar to those in HIV-negative patients.

KTP/LBO laser vaporization of the prostate.

Laser-based treatments have emerged in the past 15 years as an alternative to transurethral resection of the prostate (TURP) for treatment of symptomatic benign prostatic hyperplasia. Increasing demand for a minimally invasive procedure to alleviate lower urinary tract symptoms with greater efficacy and fewer side effects has led to the introduction of various lasers. The excellent clinical outcomes, low morbidity, technical simplicity, and cost-effectiveness of GreenLight laser photoselective vaporization have made this technology a valid and efficacious clinical alternative to TURP.

The use of sacral neuromodulation for the treatment of non-obstructive urinary retention secondary to Guillain-Barré syndrome.

Guillain-Barré syndrome, an acute autoimmune polyneuropathy and demyelinating disease, is characterized by weakness, sensory loss, areflexia, pain, autonomic dysfunction, and occasionally, micturition disturbances including voiding difficulty, urinary retention, nocturnal urinary frequency, and urge incontinence. Typically, urinary dysfunction resolves simultaneously with other neurologic deficits. We report the case of a 20-year-old woman with Guillain-Barré syndrome and persistent urinary retention 18 months following initial diagnosis. This patient is the first described in the literature to undergo successful treatment with sacral neuromodulation. Immediately following neuromodulator placement, the patient voided spontaneously and has had no voiding dysfunction or postvoid residual after 5 months of follow-up.

Prostate volume and pathologic prostate cancer outcomes after radical prostatectomy.

OBJECTIVES: To more clearly elucidate the relationship between prostate volume (PV) and prostate cancer parameters. METHODS: The Urologic Oncology Database was reviewed. A total of 3460 patients had undergone radical prostatectomy from 1988 to 2006. Of these, 2600 with complete data were included in the study and were stratified by the PV: normal (0 to 40 cm(3)), moderate (40 to 80 cm(3)), or large (greater than 80 cm(3)). The prostate cancer variables were evaluated using analysis of variance. Regression models were used to determine the role of PV in Gleason sum discordance (greater than 1 unit) controlling for prostate-specific antigen level and clinical and pathologic stage. RESULTS: Of the 2600 patients, 1453 (55.2%) had a normal, 1035 (39.8%) a moderate, and 130 (5.0%) a large PV. Patients with a normal PV were more likely to have a Gleason sum greater than 6 at biopsy (46.2%) and radical retropubic prostatectomy (68.4%) compared with patients with a moderate (39.0% and 58.9%, respectively) or a large (41.5% and 57.7%, respectively) PV (P = 0.005 and P = 0.001, respectively). Patients with a normal PV had greater rates of extraprostatic extension (32.3%) and positive margins (28.2%) compared with those with a moderate (25.5% and 22.4%, respectively) or a large (23.3% and 20.3%, respectively) PV (P = 0.002 and P = 0.005, respectively). Of all 2600 patients, 55.9% had no change between the biopsy and pathologic Gleason sum, 255 (9.8%) were downgraded, and 890 (34.3%) were upgraded. Patients with a large PV had a greater rate of downgrading (16.2%) than those with a normal (8.7%) or moderate (10.5%) PV (P = 0.01). Patients upgraded had the greatest rate of pathologically advanced disease (35.3% with Stage T3 or greater, P <0.001). On multivariate regression analysis, PV (odds ratio 0.99, P = 0.005), prostate-specific antigen level (odds ratio 1.03, P <0.001), and age (odds ratio 1.03, P <0.001) were predictors of Gleason discordance +/-2. CONCLUSIONS: The results of our study have shown that patients with a large PV (greater than 80 cm(3)) are more likely to have a lower Gleason sum, locally confined and less-aggressive pathologic disease, and were more often downgraded.

Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease.

Dysregulated apoptosis of renal tubular epithelial cells (RTEC) is an important component of the pathogenesis of several renal diseases, including HIV-associated nephropathy (HIVAN), the most common cause of chronic kidney failure in HIV-infected patients. In HIVAN, RTEC become infected by HIV-1 in a focal distribution, and HIV-1 infection has been shown to induce apoptosis in vitro. In microarray studies that used a novel renal tubular epithelial cell line from a patient with HIVAN, it was found that the ubiquitin-like protein FAT10 is one of the most upregulated genes in HIV-infected cells. Previously, FAT10 was shown to induce apoptosis in murine fibroblasts. The expression of FAT10 in HIVAN and the ability of FAT10 to induce apoptosis in human RTEC therefore were studied. This study revealed that FAT10 expression is induced after infection of RTEC by HIV-1 and that expression of FAT10 induces apoptosis in RTEC in vitro. Moreover, it was found that inhibition of endogenous FAT10 expression abrogated HIV-induced apoptosis of RTEC. Immunohistochemical studies demonstrated increased FAT10 expression in a murine model of HIVAN, in HIVAN biopsy samples, and in autosomal dominant polycystic kidney disease, another renal disease that is characterized by cystic tubular enlargement and epithelial apoptosis. These results suggest a novel role for FAT10 in epithelial apoptosis, which is an important component of the pathogenesis of many renal diseases.