The Role of Testosterone Supplemental Therapy in Opioid-Induced Hypogonadism: A Retrospective Pilot Analysis.

Chronic opioid therapy for pain management is known to induce several endocrine changes. The authors examined the effect of testosterone supplemental therapy (TST) in patients with chronic, noncancer pain undergoing opioid therapy. It was hypothesized that treatment of opioid-induced hypogonadism (OIH) can reduce opioid requirements in patients suffering from chronic pain and approve their quality of life. Over 18 months period, patients with OIH were identified in a tertiary referral pain center, Numerical Rating Scale (NRS) pain scores and daily morphine equivalent dose (MED) were the primary outcomes measured. Data were collected and comparative analysis performed between men undergoing TST versus nontreatment group. Twenty-seven OIH patients (total testosterone <300 ng/dL) were identified during the study period. TST group consists of 11 patients, while non-TST group consists of 16 patients as control cohort. Mean patient age (55 and 54.4, p = .4) and basic metabolic index (28.5 and 31.9, p = .07) in TST and non-TST groups, respectively. Mean follow-up total testosterone (ng/dL) was significantly higher after TST compared with the non-TST group (497.5 vs. 242.4 ng/dL, p = .03). Median follow-up NRS was 0 and 2 in the TST and non-TST groups ( p = .02). Mean MED (mg) decreased by 21 mg in TST group and increased by 2.5 mg in non-TST group ( p < .05). This study reports that treatment of OIH with TST can reduce opioid requirements in men with chronic pain as quantified by MED. It also confirms previous reports on the potential effects of OIH and that TST is effective in correcting opioid-induced endocrine abnormalities.

Urologic outcomes of pediatric pelvic neuroblastoma presenting in acute urinary retention.

PURPOSE: To evaluate long-term urologic outcomes of patients with pelvic neuroblastoma (NB) presenting with urinary retention. METHODS: Five cases of pelvic NB presenting with urinary retention were identified between 1971 and 2011. Clinical presentation, treatment, survival and long-term voiding outcomes were analyzed. RESULTS: All five patients presented with acute urinary retention and pelvic outlet dysfunction including bladder perforation (20%), constipation (40%), or fecal incontinence (20%). The presenting age ranged from 7 days to 4 years with female to male ratio of 3:2. Two patients presented with bilateral hydronephrosis and three patients were stage 4 at presentation. All required debulking surgery, four patients required combined anterior and posterior approaches for tumor resection, with two patients requiring concurrent laminectomy. Adjuvant or neoadjuvant chemoradiation was used in four of five cases. Follow-up ranged from 2 to 41 years. Although the long-term oncological outcome is favorable, urologic outcomes of these patients ranged from normal bladder function to the need significant reconstructive procedures. CONCLUSION: Urologic outcomes are related to pelvic nerve and organ preservation during resection more than the severity of urinary symptoms at presentation.

Comparison of transrectal and transvaginal hybrid natural orifice transluminal endoscopic surgery partial nephrectomy in the porcine model.

OBJECTIVE: To compare the feasibility of porcine transrectal (TR) and transvaginal (TV) hybrid natural orifice transluminal endoscopic surgery (NOTES) partial nephrectomy (PN), as NOTES nephrectomy has recently been performed in the porcine model. MATERIALS AND METHODS: A total of 10 female pigs (weight 45 kg) underwent TR (n = 5) or TV (n = 5) NOTES PN. The pneumoperitoneum was created by a periumbilical 12-mm trocar, through which a laparoscope was advanced for intra-abdominal visualization. For TV-NOTES PN, a gastroscope was used to obtain TV peritoneal access. For TR-NOTES PN, a horizontal incision was made 2 cm above the dentate line, and a submucosal tunnel was created in the posterior rectal wall. The gastroscope was advanced through the submucosal tunnel and retroperitoneum to the kidney, and a peritoneal window was created. For both TR- and TV-NOTES PN, the gastroscope was exchanged for the SPIDER Surgical System. Flexible dissecting instruments and hook cautery introduced through the SPIDER Surgical System were used to mobilize the kidney. A harmonic scalpel introduced periumbilically was used to excise a portion of the lower pole. LAPRA-TY-secured sutured renorrhaphy was performed, followed by TR or TV specimen extraction. RESULTS: TR- and TV-NOTES PN was successfully performed in all 10 pigs. A comparison of TR- and TV-NOTES PN revealed no significant differences in the mean access time (29.2 vs 29.6 minutes, P = .944), operative time (196.0 vs 183.0 minutes, P = .631), and estimated blood loss (59.0 vs 54.0 mL, P = .861). Necropsy did not demonstrate abdominal injuries. CONCLUSION: We have demonstrated proof-of-principle for TR and TV-NOTES PN in swine, with comparable perioperative parameters. Preclinical survival studies are requisite to assess the potential of TR-NOTES as an alternative to TV-NOTES.

RENAL nephrometry score is associated with complications after renal cryoablation: a multicenter analysis.

OBJECTIVE: To analyze outcomes and complications of percutaneous (PRC) and laparoscopic renal cryoablation (LRC) using the radius, endophytic, nearness to collecting system, anterior/posterior, and location (RENAL) nephrometry system. METHODS: Retrospective multicenter analysis of 154 consecutive patients who underwent either ultrasound-guided LRC (n = 88) or computed tomography (CT)-guided PRC (n = 66) from March 2003 to December 2011. RENAL score and demographics were compared to postoperative complications (Clavien). Multivariable analysis was carried out for factors associated with development of postprocedure complications. RESULTS: Mean age was 68 years (94 men/60 women). Median follow-up was 34 months (range 23.6-45.6 months). Mean tumor size was 2.6 ± 1 cm. Mean RENAL score was 5.2 ± 1.4. Differences in (A)nterior/posterior component and (H)ilar domain of the RENAL scores were noted, with PRC favoring posterior tumors and hilar lesions compared to LRC (P < .001 and P = .044, respectively). There were 14.9% complications, all of which were low-grade (Clavien 1,2). There were no differences in complications between LRC and PRC (15.9% vs 13.6%, P = .82). Most common complication type was hemorrhagic in 9 of 154 patients (5.8%); significant increase in the hemorrhagic complication rate was noted for patients with "N" ("nearness") component score of 2 or 3 (5/36, or 13.9%), compared to patients with "N" score of 1 (4/115 or 3.5%, P = .033). multivariable analysis demonstrated that increasing RENAL score was associated with postprocedure complications (odds ratio [OR] = 1.37, P = .025). When separated into individual domains, multivariable analysis revealed that "N" score 3 was significantly associated with postoperative complications (OR 16.15, P = .027). CONCLUSION: Increasing RENAL score was associated development of postprocedure complications after renal cryotherapy. Further investigation is requisite to elucidate the role of RENAL nephrometry score in risk stratification prior to renal cryotherapy.

Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system.

BACKGROUND: CKS257 (Salmonella typhimurium SL1344 DeltaphoP/phoQDelta aroA Deltaasd DeltastrA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag. METHODS: HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10)CFU of CKS257 and were monitored for clinical events, shedding and immune responses. RESULTS: Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >or=5 x 10(8)CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay. CONCLUSIONS: Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development.

Safety and shedding of an attenuated strain of Listeria monocytogenes with a deletion of actA/plcB in adult volunteers: a dose escalation study of oral inoculation.

Listeria monocytogenes is an intracellular bacterial pathogen which causes bacteremia and has a tropism for the central nervous system and a propensity to cause maternofetal infection. L. monocytogenes has been shown to be an effective prophylactic and a therapeutic vaccine vector for viral and tumor antigens in animal models. L. monocytogenes mutants lacking the ActA protein, which is essential for intracellular movement, are attenuated but retain immunogenicity in mice. Given the pathogenic potential of L. monocytogenes, we created an attenuated mutant strain bearing double deletions in the actA and plcB virulence genes for an initial clinical safety study of a prototype L. monocytogenes vector in adults. Twenty healthy volunteers received single escalating oral doses (10(6) to 10(9) CFU, 4 volunteers per dose cohort) of this attenuated L. monocytogenes, designated LH1169. Volunteers were monitored in the hospital for 14 days with frequent clinical checks and daily blood and stool cultures, and they were monitored for six additional weeks as outpatients. There were no positive blood cultures and no fevers attributable to the investigational inoculation. Most volunteers shed vaccine bacteria for 4 days or less, without diarrhea. One volunteer had a late positive stool culture during outpatient follow-up. Three volunteers had abnormal liver function test results temporally associated with inoculation; one could be reasonably attributed to another cause. In the highest-dose cohort, humoral, mucosal, and cellular immune responses to the investigational organism were detected in individual volunteers. Attenuated L. monocytogenes can be studied in adult volunteers without serious long-term health sequelae.