Efficacy of Repeat Midurethral Sling for Persistent or Recurrent Stress Urinary Incontinence: A Fellows Pelvic Research Network Study.

OBJECTIVE: The objective of this study is to compare quality of life and success rates of repeat midurethral slings (RMUS) using retropubic (RP) and transobturator (TO) routes. MATERIALS AND METHODS: Multicenter retrospective cohort with prospective follow-up of patients undergoing RMUS from 2003 to 2016. Prospective Urinary Distress Inventory (UDI-6) and Patient Global Impression of Improvement (PGI-I) were collected by phone. Primary outcome was success of repeat sling by approach (RP vs TO), defined as responses of no to UDI-6 number 3 and very much better or much better on PGI-I. RESULTS: A total of 122 patients prospectively completed UDI-6. Average ± SD time to failure after initial sling was 51.6 ± 56.1 months; mean follow-up after repeat sling was 30.7 months. Route of initial sling was RP 30.3%, TO 49.2%, and minisling 16.4%. Of the patients, 55.8% met our success definition following RMUS. About 71.3% were very much better or much better on PGI-I, and 30.3% reported stress urinary incontinence (SUI) on UDI-6. Of the RMUS, 73.8% were RP versus 26.2% TO.There was no difference in success between repeat RP and TO routes (53.3% versus 63.3%, P = 0.34), nor for individual components: PGI-I response of very much better or much better (68.9% vs 78.1%), UDI-6 total score (25.9 vs 22.7, P = 0.29), or SUI on UDI-6 number 3 (32.2% vs 25.0%, P = 0.45), although the predetermined sample size was not met. No predictors of success or failure of RMUS were identified. CONCLUSIONS: Majority of patients are very much better or much better after RMUS, although 30% still report bothersome SUI. No difference in success was observed between RP and TO RMUS.

Patients' Knowledge of and Attitude Toward Robotic Surgery for Pelvic Organ Prolapse.

OBJECTIVES: Robotic sacrocolpopexy for pelvic organ prolapse (POP) has increased, along with marketing and media coverage. It is unknown whether this exposure influences patients' opinions on POP repair. This study describes the preference for and knowledge of robotic surgery in women with POP. METHODS: We performed a cross-sectional survey of new patients presenting with POP at 7 academic sites. Subjects had no prior surgical counseling. A self-administered questionnaire was designed to investigate robotic surgery knowledge, preference, and exposure. Subjects expressed their preferred route of POP repair (robotic, vaginal, abdominal, laparoscopic, or no preference). Knowledge was determined by the number of correctly answered questions (range, 0-7). Perception of robotic surgery was compared with other surgical routes. RESULTS: One hundred seventy-six subjects were included. Most had no surgical preference (66.3%), whereas 27.3% preferred nonrobotic and 6.4% preferred robotic routes. The mean knowledge score was 2.3 (SD, 1.7). Women preferring robotic surgery were more likely to view it as faster than laparoscopic surgery (P < 0.001). These same subjects did not perceive any advantages for robotic surgery related to blood loss, pain, and organ injury (P > 0.05). Most reported no prior exposure to robotic surgery information (56.2%) or advertisements (65.2%). Those with prior exposure most frequently obtained information via the Internet and encountered hospital advertisements. CONCLUSIONS: The majority of women with POP reported no preference for robotic approach to POP surgery. Knowledge about robotic surgery was low, even among subjects who expressed preference. Comprehensive counseling may help patients make informed decisions even when surgical preferences exist.

Social networking and Internet use among pelvic floor patients: a multicenter survey.

BACKGROUND: Internet resources are becoming increasingly important for patients seeking medical knowledge. It is imperative to understand patient use and preferences for using the Internet and social networking websites to optimize patient education. OBJECTIVES: The purpose of this study was to evaluate social networking and Internet use among women with pelvic floor complaints to seek information for their conditions as well as describe the likelihood, preferences, and predictors of website usage. STUDY DESIGN: This was a cross-sectional, multicenter study of women presenting to clinical practices of 10 female pelvic medicine and reconstructive surgery fellowship programs across the United States, affiliated with the Fellows' Pelvic Research Network. New female patients presenting with pelvic floor complaints, including urinary incontinence, pelvic organ prolapse, and fecal incontinence were eligible. Participants completed a 24 item questionnaire designed by the authors to assess demographic information, general Internet use, preferences regarding social networking websites, referral patterns, and resources utilized to learn about their pelvic floor complaints. Internet use was quantified as high (≥4 times/wk), moderate (2-3 times/wk), or minimal (≤1 time/wk). Means were used for normally distributed data and medians for data not meeting this assumption. Fisher's exact and χ2 tests were used to evaluate the associations between variables and Internet use. RESULTS: A total of 282 surveys were analyzed. The majority of participants, 83.3%, were white. The mean age was 55.8 years old. Referrals to urogynecology practices were most frequently from obstetrician/gynecologists (39.9%) and primary care providers (27.8%). Subjects were well distributed geographically, with the largest representation from the South (38.0%). Almost one third (29.9%) were most bothered by prolapse complaints, 22.0% by urgency urinary incontinence, 20.9% by stress urinary incontinence, 14.9% by urgency/frequency symptoms, and 4.1% by fecal incontinence. The majority, 75.0%, described high Internet use, whereas 8.5% moderately and 4.8% minimally used the Internet. Women most often used the Internet for personal motivations including medical research (76.4%), and 42.6% reported Google to be their primary search engine. Despite this, only 4.9% primarily used the Internet to learn about their pelvic floor condition, more commonly consulting an obstetrician-gynecologist for this information (39.4%). The majority (74.1%) held a social networking account, and 45.9% visited these daily. Nearly half, 41.7%, expressed the desire to use social networking websites to learn about their condition. Women <65 years old were significantly more likely to have high Internet use (83.4% vs 68.8%, P = .018) and to desire using social networking websites to learn about their pelvic floor complaint (P = .008). The presenting complaint was not associated with Internet use (P = .905) or the desire to use social networking websites to learn about pelvic floor disorders (P = .201). CONCLUSION: Women presenting to urogynecology practices have high Internet use and a desire to learn about their conditions via social networking websites. Despite this, obstetrician-gynecologists remain a common resource for information. Nonetheless, urogynecology practices and national organizations would likely benefit from increasing their Internet resources for patient education in pelvic floor disorders, though patients should be made aware of available resources.

Transurethral use of a nephroscope significantly AIDS in the surgical management of an intrauterine device eroding into the bladder.

BACKGROUND: Intravesical migration of an intrauterine device (IUD) is a rare occurrence. The IUD becomes the nidus for calcification. Three approaches to remove the device include the use of open cystolithotomy, transurethral grasping forceps, or minimally invasive laparoscopy. CASE: A 50-year-old woman presented with vague abdominal pain and recurrent urinary tract infections. She was found to have an intravesical migration or malplacement of an IUD which was unretrievable 20 years ago and was encrusted with a calculus formation. We removed the foreign body through a transurethral approach aided by the use of a nephroscope which allowed for easy access of laparoscopic scissors and grasping forceps. CONCLUSIONS: The transurethral approach with the use of a nephroscope significantly aids in the removal of an IUD embedded into the bladder wall.

Prolapse of a single system large ureterocele containing multiple stones in a pregnant woman.

Periurethral masses are uncommon in adult women, with little guidance on initial management. We describe a case of a 29-year-old pregnant woman with a single-system ureterocele prolapse complicated by multiple calculi ranging from 1 to 2.5 cm.

Kinetics of tumor destruction by chimeric antigen receptor-modified T cells.

The use of chimeric antigen receptor (CAR)-modified T cells as a therapy for hematologic malignancies and solid tumors is becoming more widespread. However, the infusion of a T-cell product targeting a single tumor-associated antigen may lead to target antigen modulation under this selective pressure, with subsequent tumor immune escape. With the purpose of preventing this phenomenon, we have studied the impact of simultaneously targeting two distinct antigens present on tumor cells: namely mucin 1 and prostate stem cell antigen, both of which are expressed in a variety of solid tumors, including pancreatic and prostate cancer. When used individually, CAR T cells directed against either tumor antigen were able to kill target-expressing cancer cells, but tumor heterogeneity led to immune escape. As a combination therapy, we demonstrate superior antitumor effects using both CARs simultaneously, but this was nevertheless insufficient to achieve a complete response. To understand the mechanism of escape, we studied the kinetics of T-cell killing and found that the magnitude of tumor destruction depended not only on the presence of target antigens but also on the intensity of expression-a feature that could be altered by administering epigenetic modulators that upregulated target expression and enhanced CAR T-cell potency.

Comparison of transfusion requirements between open and robotic-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To determine whether robotic-assisted laparoscopic radical prostatectomy (RALP) is associated with a lower transfusion rate than radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: In this cohort study, we evaluated 1244 consecutive patients who underwent RALP (830) or RRP (414) between June 2003 and July 2006. Demographics, clinical characteristics, pathology, blood loss and transfusion data were collected prospectively. Groups were compared for baseline characteristics, blood loss, change in haematocrit and transfusion using univariate statistics, and an exploratory multivariate model was developed. RESULTS: RALP was associated with lower blood loss (median 100 vs 450 mL, P < 0.001) and a smaller change in haematocrit (median 7% vs 10%, P < 0.001) than RRP. Although both groups had low transfusion rates, the RALP group required fewer transfusions than the RRP group (0.8% vs 3.4%, P= 0.002). On univariate analysis, surgical approach (RRP vs RALP), estimated blood loss ≥500 mL and change in haematocrit ≥10% were the only the significant predictors of transfusion. In the exploratory multivariate model RALP was the only significant predictor of reduced need for transfusion, with an odds ratio of 0.23 (95% confidence interval 0.09-0.58; P= 0.002). CONCLUSIONS: This study shows that RALP is associated not only with less blood loss and a smaller decrease in haematocrit, but also a decreased need for transfusion.

Diverse mechanisms and consequences of immunoadoption of neuromediator systems.

Modern investigations of the mechanisms of both neuroregulation of immunity and neural effects of immune reactions have focused on identification of the mediators, their receptors, and signal transduction pathways in both systems. Less attention has been directed to delineation of the tissue context of neuroregulation of immunity that determines the principal sources of neuromediators, the physiological consequences of integration of neural and immune activities, and possible approaches to pharmacological manipulation. To illustrate these points, we describe here the corticotropin-releasing hormone (CRH) and vasoactive intestinal peptide (VIP) axes. When generated by the hypothalamus in response to inflammation or other stresses, CRH is immunosuppressive through its ability to increase levels of glucocorticoids and catecholamines. In contrast, CRH from peripheral nerves and immune accessory cells is immunostimulatory in tissue immune responses through direct effects on macrophages and lymphocytes. VIP released from several sets of nerves is immunosuppressive as a result of actions on macrophages and T cells in lymphoid organs, whereas VIP from immune cells in local tissue responses to antigen enhances development of some types of memory T cells and effector Th17 cells. Better understanding of how tissue context establishes the nature of neuroregulation of immunity will improve neuropharmacological and other neurotherapeutic approaches to immune diseases.

Effect of a large prostate gland on open and robotically assisted laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the outcomes based on gland size between robotically assisted radical prostatectomy (RALP) and open RP (RRP), as larger prostates might increase the difficulty of RP. PATIENTS AND METHODS: We reviewed 660 patients who had RALP and 340 who had RRP from May 2003 to August 2006; the patients were divided into two groups, with a prostate of >75 and or=75 g had fewer positive margins than smaller glands, regardless of surgical technique. There was also a significant decrease in positive margin rate in among prostates of >75 g in favour of RALP. Thus, RALP appears to be comparable with RRP for patients with large glands, and might reduce the positive margin rate.

A comparison of the incidence and location of positive surgical margins in robotic assisted laparoscopic radical prostatectomy and open retropubic radical prostatectomy.

PURPOSE: Surgical technique, patient characteristics and method of pathological review may influence surgical margin status. We evaluated the incidence and location of positive surgical margins in 200 sequential robotic assisted laparoscopic radical prostatectomy and 200 sequential open radical retropubic prostatectomy cases. MATERIALS AND METHODS: From July 2002 until December 2006 a total of 1,747 patients underwent radical prostatectomy at our institution (robotic assisted laparoscopic radical prostatectomy in 1,238, radical retropubic prostatectomy in 509). From these we selected the last 200 consecutive radical retropubic prostatectomies and 200 robotic assisted laparoscopic radical prostatectomies performed before August 2006. Preoperative clinical characteristics including age, clinical stage, prostate specific antigen and Gleason score were evaluated. Postoperatively pathological specimens were assessed for specimen weight, Gleason score, tumor volume, pathological stage and margin status. The incidence and location of positive surgical margins were compared between robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy. RESULTS: Patients undergoing robotic assisted laparoscopic radical prostatectomy compared to radical retropubic prostatectomy had more favorable tumor characteristics including lower prostate specific antigen, clinical stage and Gleason score. No statistically significant differences were found between groups for prostate volume or tumor volume. However, tumor volume as a percentage of prostate volume was higher among radical retropubic prostatectomy compared to robotic assisted laparoscopic radical prostatectomy cases (17.7% vs 13%, p = 0.001). The overall incidence of positive surgical margins was significantly lower among the robotic assisted laparoscopic radical prostatectomy compared to radical retropubic prostatectomy cases (15% vs 35%, p <0.001). The incidence of positive surgical margins according to pathological stage for robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy cases was 16 of 171 (9.4%) vs 33 of 137 (24.1%) for pT2 (p <0.001) and 14 of 28 (50%) vs 36 of 60 (60%) for pT3. In both groups the apex was the most common site of positive surgical margins with 52% in the robotic assisted laparoscopic radical prostatectomy group vs 37% in the radical retropubic prostatectomy group (p >0.05). CONCLUSIONS: In the hands of surgeons experienced in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy, there was a statistically significant lower positive margin rate for patients undergoing robotic assisted laparoscopic radical prostatectomy. The most common location of a positive surgical margin in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy cases was at the apex. Patients treated with radical retropubic prostatectomy had higher risk features which may have independently influenced these results. The method of pathological specimen analysis and reporting may account for the higher positive margin rates in both groups compared to some reports.

Urothelial carcinoma of the bladder metastatic to bone marrow presenting as isolated thrombocytopenia.

The skeletal system is a frequent site for metastases of urothelial carcinoma (UC) of the bladder (22-37%). Of those cases involving bone, the marrow is infiltrated in 27% of patients. Imaging modalities, such as X-ray and CT, will detect gross skeletal lesions in the vast majority of these patients with bone marrow involvement, however, most patients with bone involvement are symptomatic at presentation. Additionally, there have been few reports in the literature of bone marrow metastases from UC presenting with isolated thrombocytopenia. This case report describes the case of a 53-year-old male with muscle-invasive transitional cell carcinoma of the bladder treated with cystoprostatectomy. Preoperative evaluation was significant only for mild thrombocytopenia. Standard workup for metastatic bony involvement, which included history, physical, chest X-ray, and whole body CT, was negative. Postoperatively, the patient's thrombocytopenia worsened and he bled diffusely from his pelvic bed. Bone marrow biopsy was obtained and showed the entire marrow cavity to be filled with metastatic transitional cells. In the event of a similar future presentation of isolated thrombocytopenia in the setting of invasive UC, the clinician should consider a bone marrow biopsy, in addition to the standard workup for metastatic bony involvement, prior to proceeding with any surgical intervention.

Immunoeffector and immunoregulatory activities of vasoactive intestinal peptide.

Vasoactive intestinal peptide (VIP) and its two G protein-coupled receptors, VPAC1R and VPAC2R, are prominent in the immune system and potently affect T cells and macrophages. VPAC1Rs are expressed constitutively by blood and tissue T cells, with an order of prevalence of Th2>Th1>>Ts, and transmit signals suppressive for migration, proliferation and cytokine production. Immune activation of T cells downregulates VPAC1Rs and upregulates VPAC2Rs. VPAC2Rs mediate T cell chemotaxis, stimulation of some Th2-type cytokines, and inhibition of some Th1-type cytokines. A tentative hypothesis that the VIP-VPAC2R axis is the major neuroregulator of Th2/Th1 balance has been confirmed by finding an increased ratio in CD4 T cells of transgenic (TG) mice, expressing high levels of VPAC2Rs, and a decreased ratio in CD4 T cells of VPAC2R-null (K/O) mice. VPAC2R TG mice exhibit an allergic phenotype, whereas the K/O mice are hypoallergic and have heightened delayed-type hypersensitivity. The mechanisms of VIP-VPAC2R effects include decreased Th2 apoptosis, increased Th2-type cytokine production, and greater generation of Th2 memory cells. VPAC2R antagonists are being developed to alleviate allergic diseases and strengthen effector Th1 cell-mediated immunoprotection.