Robot-assisted laparoscopic sacrocolpopexy with autologous fascia lata: technique and initial outcomes.

INTRODUCTION AND HYPOTHESIS: Pelvic reconstructive surgery is increasingly being performed with autologous grafts to avoid complications of synthetic mesh and improve the durability of a native tissue repair. Autologous fascia lata (AFL) provides a reliable source of robust connective tissue to improve surgical outcomes. We present our technique and initial experience with performing robotic sacrocolpopexy (RSC) augmented with AFL. METHODS: A retrospective review was conducted of patients who underwent RSC with AFL between January 2015 and November 2017. Outcomes evaluated include recurrence of prolapse on physical examination, prolapse symptoms, urinary incontinence, patient satisfaction based on the Patient Global Impression of Improvement (PGI-I) and complications. RESULTS: Twelve patients were identified with a median age of 68 years (range, 46-77 years) at the time of RSC with AFL. Eleven patients had a history of prior sling and/or vaginal mesh. The median operative time was 225 min (177-302 min). There were no intra- or postoperative complications. After a median follow-up of 14.7 months (5.7 to 39 months), the median PGI-I response was 2 (range, 1-3, very much to a little better). No recurrent or persistent apical prolapse was observed. Three patients (25%) reported recurrence of sensation of a vaginal bulge, which were all due to anterior vaginal wall prolapse. CONCLUSIONS: RSC can be performed with AFL and should be considered in patients with a history of mesh complications. Overall patient satisfaction was high. While these short-term outcomes are encouraging, further studies are needed to assess long-term durability of anatomic results.

S-nitrosylation of endothelial nitric oxide synthase impacts erectile function.

Neuronal and endothelial nitric oxide synthases (nNOS and eNOS respectively) play major roles in generating the nitric oxide bioactivity necessary for erectile function. S-nitrosylation has been shown to regulate NOS activity. The presence of S-nitrosylated NOS in the penis and the impact of NOS S-nitrosylation/denitrosylation on erectile function were examined. S-nitrosylated forms of NOS were identified by biotin-switch assay followed by western blot analysis. Erectile function in S-nitrosoglutathione reductase deficient (GSNO+/-) and null (GSNO-/-) mice were assessed by continuous cavernous nerve electrical stimulation (CCNES). Glutathione ethyl ester (GSHee) was used to manipulate S-nitrosylated NOS levels. Immunohistological and immunofluorescence analyses were used to identify the location of eNOS and GSNO-R in corporal tissue. eNOS and nNOS were S-nitrosylated in unstimulated penises of the mice. CCNES resulted in a time-dependent increase in eNOS S-nitrosylation with peak eNOS S-nitrosylation observed during detumescence. S-nitrosylated nNOS levels were unchanged. Intracorporal injection of GSHee reduced S-nitrosylated eNOS levels, enhancing time to maximum intracorporal pressure (ICP). eNOS and GSNO-R co-localize to the endothelium of the corpus cavernosum in the mouse and the human. ICP measurements obtained during CCNES demonstrate GSNO-R+/- and GSNO-R-/- animals cannot maintain an elevated ICP. Results suggest eNOS S-nitrosylation/denitrosylation is an important mechanism regulating eNOS activity during erectile function. GSNO-R is a key enzyme involved in the eNOS denitrosylation. The increase in eNOS S-nitrosylation (inactivation) observed with tumescence may begin a cycle leading to detumescence. Clinically this may indicate that alterations in the balance of S-nitrosylation/denitrosylation either directly or indirectly contribute to erectile dysfunction.

Suprameatal urethrolysis with Martius flap for refractory bladder outflow obstruction following stress incontinence surgery in females.

AIMS: To present our technique of suprameatal urethrolysis with Martius flap (SMUM) and outcomes of this procedure for refractory female bladder outflow obstruction (BOO). METHODS: A retrospective chart review was performed to identify female patients who underwent SMUM between January 2010 and August 2016 after failed transvaginal urethrolysis (TVU) for BOO due to prior stress urinary incontinence (SUI) surgery. The primary outcome measure was surgical success defined as patient ability to void volitionally without need for catheterization or additional surgery for BOO. Secondary outcomes assessed included perioperative outcomes, intraoperative and 30-day complications, change in post-void residual volume (PVR), resolution of urge urinary incontinence (UUI), incidence of recurrent SUI, and treatment for any urinary incontinence. RESULTS: Eleven patients were identified. After a median follow-up of 10.8 months (range 3.1-20.1), the procedure was successful in nine patients (82%). Postoperative median PVR was 29 cc (range 0-425) and median change in PVR was a 280 cc (range 29-1050) decrease (P < 0.01). Among the seven patients who required catheterization preoperatively, five patients (71%) recovered volitional voiding. Two patients (18%) continued to require indwelling or intermittent catheterization and underwent additional surgery for BOO. SUI recurred in one patient (9%). UUI persisted in all four patients who reported this preoperatively. CONCLUSIONS: SMUM is successful in improving or relieving refractory BOO in this challenging patient population. After TVU, we believe that Martius flap interposition is critical to preventing recurrent fixation of the urethra to the pubic bones and thus achieving improved voiding.

Robotic Sacrocolpopexy-Is It the Treatment of Choice for Advanced Apical Pelvic Organ Prolapse?

PURPOSE OF REVIEW: Pelvic organ prolapse (POP) is a highly prevalent condition among women that, although non-life threatening, can significantly impact daily activities and quality of life (QOL). Sacrocolpopexy (SC) has been touted by many as the "gold standard," citing superior anatomic success rates compared to transvaginal approaches for apical prolapse repair. In line with current trends throughout the surgical field, robotic-assisted laparoscopic sacrocolpopexy (RSC) has rapidly gained popularity. This review will present the most contemporary evidence examining RSC and discuss whether it has met criteria to qualify as the "treatment of choice" for advanced apical vaginal prolapse. RECENT FINDINGS: Recent findings support the superior durability of SC for apical prolapse repair compared to native tissue vaginal approaches. Recent evidence demonstrates that anatomic outcomes of minimally invasive sacrocolpopexy, including RSC, are no different than those of traditional ASC. Low quality evidence suggests lower rates of dyspareunia with SC compared to vaginal repairs. RSC may be cost-effective when compared to ASC. When compared to LSC, however, RSC is more expensive and associated with longer operating times. RSC is an excellent option for many women who desire the most durable option for definitive repair of advanced apical POP.

Complete Excision of Sacrocolpopexy Mesh With Autologous Fascia Sacrocolpopexy.

OBJECTIVE: To evaluate the safety and short-term efficacy of complete sacrocolpopexy mesh excision with concomitant autologous fascia sacrocolpopexy. METHODS: A retrospective cohort study of patients undergoing complete sacrocolpopexy mesh excision and concomitant autologous fascia sacrocolpopexy from March 2013 to September 2016 was conducted. The primary objective was assessment of perioperative outcomes including complications within 60 days of surgery. The secondary outcome measure was surgical success defined as no need for retreatment by either surgery for apical prolapse or pessary. RESULTS: Nineteen patients were identified. Median patient age was 56 years old (range 35-78). Median time from mesh placement to surgical excision was 4.5 years (0-13). Indications for mesh excision included refractory pelvic pain in 18 patients (95%), symptomatic mesh exposure in 8 patients (42%), and bilateral ureteral obstruction with ureterovaginal fistula in 1 patient (5%). Median operative time, estimated blood loss, and length of hospital stay were 228 minutes (133-362), 200 mL (50-1000), and 5 days (2-9), respectively. The rate of minor and major complications within 60 days was 36.8% and 5.3%, respectively. There were no cases of bladder or bowel injury. At a median follow-up of 9.9 months (2.4-39) no patient required secondary surgery for apical vaginal prolapse or retreatment with pessary. CONCLUSION: Complete sacrocolpopexy mesh excision with concomitant autologous fascia sacrocolpopexy can be accomplished safely with a low rate of major complications. These are short-term findings and longer follow-up of anatomic and functional outcomes is needed.

Comparison of Times to Ureteral Efflux after Administration of Sodium Fluorescein and Phenazopyridine.

PURPOSE: There is currently a national shortage of indigo carmine. In efforts to identify the most efficient aid for visualizing ureteral efflux intraoperatively we investigated the time to excretion of phenazopyridine vs a newly identified alternative, sodium fluorescein. MATERIALS AND METHODS: We analyzed prospectively collected data on a cohort of women who underwent pelvic reconstructive surgery in 2015. Per provider preference patterns a number of patients were administered 200 mg phenazopyridine orally with a sip of water 1 hour prior to the start of operative time. Other patients were given 0.5 ml 10% sodium fluorescein intravenously in the operating room. In all cases time was measured between the administration of the agent and the visualization of color changes consistent with agent efflux in an indwelling catheter, which was placed at the start of the operation. Differences in excretion times between the groups were compared with the Wilcoxon rank sum test. RESULTS: Seven women received phenazopyridine and 5 received sodium fluorescein. Mean excretion time was significantly longer in the phenazopyridine group compared to the sodium fluorescein group (81.9 vs 5.1 minutes, p = 0.0057). Median excretion time for phenazopyridine was 70 minutes (range 59 to 127) and for sodium fluorescein it was 5 minutes (range 3 to 9). CONCLUSIONS: Sodium fluorescein is excreted significantly faster in the operating room compared to phenazopyridine. Depending on the cost of these agents at an institution, in addition to the desire to decrease operative time, this may impact practice patterns and agent selection.

The role of regulatory proteins and S-nitrosylation of endothelial nitric oxide synthase in the human clitoris: implications for female sexual function.

INTRODUCTION: During female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown. AIM: To identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow. METHODS: Immunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES). MAIN OUTCOME MEASURES: Localization of eNOS regulatory proteins and clitoral blood flow. RESULTS: eNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow. CONCLUSIONS: Several key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.

Differential expression and tumor necrosis factor-mediated regulation of TNFRSF11b/osteoprotegerin production by human melanomas.

Tumors escape host immune responses, in part, through the release of immunomodulatory factors and decoy receptors into their microenvironment. Several cancers express surface-bound and soluble members of the tumor necrosis factor (TNF) receptor superfamily, including TNFRSF11b/osteoprotegerin (OPG). In its physiologic role, OPG regulates bone remodeling through competition for osteoclast-activating cytokines and protects newly forming bone from T cell-mediated apoptosis. In multiple tumor types, OPG production is associated with an aggressive phenotype and increased metastasis to bone, but no study has examined OPG production in human metastatic melanoma. We demonstrate that a significant proportion of human metastatic melanomas constitutively produces OPG through a mechanism governed by membrane-bound TNF-α signaling through TNF receptor 1 (TNFR1). These observations both define a specific mechanism that regulates melanoma production of OPG and establish a new molecular target for the therapeutic regulation of OPG.

Psychosocial comorbidities and obesity are associated with lower urinary tract symptoms in children with voiding dysfunction.

PURPOSE: There is emerging awareness of comorbid psychosocial characteristics in children with lower urinary tract dysfunction. To explore the prevalence of these comorbidities and their relationship to lower urinary tract symptoms, we examined the psychosocial comorbidities and body mass index of children with lower urinary tract dysfunction. MATERIALS AND METHODS: We prospectively collected data on all new patients 6 to 17 years old with nonneurogenic lower urinary tract dysfunction who presented to a single nurse practitioner in 2011. Parents completed a 21-question lower urinary tract symptom score based on a validated questionnaire and a psychosocial questionnaire that screened for stressful life events and psychological diagnoses. We examined the correlation of body mass index percentile and psychosocial comorbidities with lower urinary tract symptom score. RESULTS: Of the 358 patients 28.5% were obese, 31.8% had a recent life stressor and 22.9% had a comorbid psychiatric disorder. Younger age correlated with a higher lower urinary tract symptom score (r = -0.34, p <0.0001). Children with a recent life stressor (p = 0.049), psychiatric disorder (p = 0.0026) or the 2 comorbidities (p = 0.039) had a significantly higher lower urinary tract symptom score than children without comorbidities. Underweight and obese children had a significantly higher lower urinary tract symptom score than healthy weight and overweight children (p = 0.009). CONCLUSIONS: Almost a third of the patients in our study were obese. More than 40% of the children had a psychiatric disorder and/or recent life stressor. Younger age, an underweight or obese body mass index and a recent stressful life event or psychiatric disorder correlated with a higher lower urinary tract symptom score. This study supports previous recommendations to screen for psychosocial comorbidities and obesity during the evaluation of pediatric lower urinary tract dysfunction.

Pediatric robotic extravesical ureteral reimplantation: comparison with open surgery.

PURPOSE: Robotic assisted laparoscopic extravesical ureteral reimplantation is becoming more widely used as an alternative to open reimplantation. To date, no direct comparison to the open approach in a similar cohort exists. We review a single surgeon experience and compare the outcomes of robotic assisted laparoscopic extravesical ureteral reimplantation and open ureteral reimplantation in children with vesicoureteral reflux. MATERIALS AND METHODS: We retrospectively reviewed the charts of 25 pediatric patients (mean age 69 months, range 3 to 144) who underwent robotic assisted laparoscopic extravesical ureteral reimplantation for unilateral or bilateral vesicoureteral reflux between February 2006 and December 2009. A total of 25 patients undergoing open cross-trigonal ureteral reimplantation (mean age 50 months, range 8 to 110) during the same period were used for comparison. All cases were performed by a single surgeon. RESULTS: There were no conversions or intraoperative complications. There was no correlation between age or weight and operative time, length of stay or total analgesia used. Mean operative time was 12% longer in the robotic group vs controls (p <0.05). Mean length of stay (33 vs 53 hours) and pain medication usage were significantly less in the robotic group (p <0.001). Time to first oral intake was not significantly different. There were 3 episodes of transient urinary retention in the robotic group, all in patients undergoing bilateral reimplantation. The overall success rate, defined as no radiographic or clinical evidence of residual reflux, was 97% for robotic assisted laparoscopy after a mean followup of 16 months, compared to 100% for open reimplantation. CONCLUSIONS: Robotic assisted laparoscopic extravesical ureteral reimplantation appears to be a safe and efficacious option for repair of vesicoureteral reflux. This early series shows success rates similar to the open approach. We observed decreased length of stay and use of postoperative narcotics. These findings may serve to justify further exploration of this technology and to provide data for design of a prospective trial, although the relative value of specific reductions in morbidity will need to be defined.

Defective human leukocyte antigen class I-associated antigen presentation caused by a novel beta2-microglobulin loss-of-function in melanoma cells.

The major histocompatibility complex class I molecules consist of three subunits, the 45-kDa heavy chain, the 12-kDa beta(2)-microglobulin (beta(2)m), and an approximately 8-9-residue antigenic peptide. Without beta(2)m, the major histocompatibility complex class I molecules cannot assemble, thereby abolishing their transport to the cell membrane and the subsequent recognition by antigen-specific T cells. Here we report a case of defective antigen presentation caused by the expression of a beta(2)m with a Cys-to-Trp substitution at position 25 (beta(2)m(C25W)). This substitution causes misfolding and degradation of beta(2)m(C25W) but does not result in complete lack of human leukocyte antigen (HLA) class I molecule expression on the surface of melanoma VMM5B cells. Despite HLA class I expression, VMM5B cells are not recognized by HLA class I-restricted, melanoma antigen-specific cytotoxic T lymphocytes even following loading with exogenous peptides or transduction with melanoma antigen-expressing viruses. Lysis of VMM5B cells is restored only following reconstitution with exogenous or endogenous wild-type beta(2)m protein. Together, our results indicate impairment of antigenic peptide presentation because of a dysfunctional beta(2)m and provide a mechanism for the lack of close association between HLA class I expression and susceptibility of tumor cells to cytotoxic T lymphocytes-mediated lysis in malignant diseases.