Unconventional mechanism of action and resistance to rapalogs in renal cancer.

mTORC1 is aberrantly activated in renal cell carcinoma (RCC) and is targeted by rapalogs. As for other targeted therapies, rapalogs clinical utility is limited by the development of resistance. Resistance often results from target mutation, but mTOR mutations are rarely found in RCC. As in humans, prolonged rapalog treatment of RCC tumorgrafts (TGs) led to resistance. Unexpectedly, explants from resistant tumors became sensitive both in culture and in subsequent transplants in mice. Notably, resistance developed despite persistent mTORC1 inhibition in tumor cells. In contrast, mTORC1 became reactivated in the tumor microenvironment (TME). To test the role of the TME, we engineered immunocompromised recipient mice with a resistance mTOR mutation (S2035T). Interestingly, TGs became resistant to rapalogs in mTORS2035T mice. Resistance occurred despite mTORC1 inhibition in tumor cells and could be induced by coculturing tumor cells with mutant fibroblasts. Thus, enforced mTORC1 activation in the TME is sufficient to confer resistance to rapalogs. These studies highlight the importance of mTORC1 inhibition in nontumor cells for rapalog antitumor activity and provide an explanation for the lack of mTOR resistance mutations in RCC patients.

Comparing costs associated with management of antibiotic-recalcitrant recurrent urinary tract infections for one year pre- and post-electrofulguration.

INTRODUCTION: To quantify and compare recurrent urinary tract infection costs between 1 year before and 1 year after electrofulguration. METHODS: Following IRB approval, a well-characterized cohort of non-neurogenic women with >3 symptomatic urinary tract infections (UTIs)/year, a negative upper and lower urinary tract evaluation, and inflammatory bladder lesions (cystitis) on office cystoscopy who underwent fulguration of these lesions was analyzed. Cost of visits, imaging, labs, and medications were summed for 1-year pre- and post-fulguration using the Medicare Physician Fee Schedule, local pharmacy pricing, and institutional expenses. Before fulguration, all patients underwent clinic visit, noninvasive flow study, and flexible cystoscopy, and post-fulguration, 6-week follow-up visit and 6-month cystoscopy. RESULTS: Ninety-three women met study criteria (mean age 64), with 100% 1-year follow-up. Before fulguration, 73% of patients used daily antibiotic suppression, 6% self-start antibiotics, and 5% postcoital prophylaxis. Some also used vaginal estrogens (17%), urinary analgesics (13%), and cranberry or d-mannose supplements (7%). At 1 year post-fulguration, 82% had 0-1 infections and no cystoscopy evidence of cystitis, while 14% required additional fulguration for new cystitis sites and recurrent infections. Patients had on average 0.7 infections in the 1-year post-fulguration, which was significantly lower than pre-fulguration (p < 0.05). Mean 1-year pre-fulguration cost was $1328 (median $1071, range $291-$5564). Mean 1-year post-fulguration cost was $617 (median $467, range $275-$4580). On average, post-fulguration costs were $710 lower than pre-EF (p < 0.05). CONCLUSION: For women with antibiotic-refractory recurrent urinary tract infections and cystoscopy evidence of cystitis, fulguration was associated with a significant reduction in UTI-related costs in the 1-year post-fulguration.

Very Long-term Outcomes After Electrofulguration for Antibiotic-refractory Recurrent Urinary Tract Infections in a Predominantly Menopausal Cohort of Women.

PURPOSE: Antibiotic-refractory recurrent urinary tract infections are challenging to manage. Prior studies have shown that, in selected patients, electrofulguration of cystitis may disrupt potential nidus of recurrent urinary tract infections. We report on long-term outcomes of electrofulguration in women with at least 5 years of follow-up. MATERIALS AND METHODS: Following Institutional Review Board approval, we analyzed a cohort of nonneurogenic women with ≥3 symptomatic recurrent urinary tract infections/y and inflammatory lesions on cystoscopy who underwent electrofulguration, excluding those with alternate identifiable etiology for recurrent urinary tract infections or less than 5-year follow-up. Preoperative characteristics, antibiotic regimens, and annual urinary tract infections were reported. Primary outcome was clinical cure (0-1 urinary tract infection/y), improvement (>1 and <3/y) or failure (≥3/y) at last follow-up. Secondary outcomes included need for antibiotics or repeat electrofulguration. A subanalysis was performed for women with >10-year follow-up. RESULTS: From 2006 to 2012, 96 women met study criteria with median age 64. Median follow-up was 11 years (IQR: 10-13.5); 71 women had >10-year follow-up. Prior to electrofulguration, 74% used daily antibiotic suppression, 5% used postcoital prophylaxis, 14% used self-start therapy, and 7% were not on prophylaxis. At last post-electrofulguration visit, 72% of women were cured, 22% improved, and 6% failed. Antibiotic usage decreased post-electrofulguration (P < .05). Five percent were on continuous antibiotics at last follow-up as compared to 74% on continuous antibiotics pre-electrofulguration (McNemar P < .05). Nineteen percent of women underwent a repeat electrofulguration. CONCLUSIONS: In menopausal women with over 5-year follow-up after electrofulguration for antibiotic-refractory recurrent urinary tract infections, there appears to be durable clinical cure and improvement, with decreased need for long-term antibiotics.

Empiric versus culture-based antibiotic therapy for UTIs in menopausal women.

PURPOSE: To assess the benefits and risks associated with empiric prescription of antibiotic therapy for treatment of a urinary tract infection (UTI). METHODS: Following IRB approval menopausal women presenting with a symptomatic UTI to a single urology clinic were prospectively assigned to one of the two treatment groups based on day of presentation: culture-based treatment (CB) (Monday, Tuesday, Wednesday) or empiric treatment (ET) (Thursday, Friday) and started on nitrofurantoin (NF) pending culture results. Both groups were contacted at 7 and 14 days following treatment. Side effects and answers to a standardized questionnaire (UTISA) were recorded. Success was defined as a total UTISA score < 3. Any NF retreatment, use of another antibiotic therapy, or extension of the original antibiotic course was considered treatment failures. RESULTS: From July 2020 to March 2022, 65 women with 80 UTI events were included in the study, with CB treatment used for 60 UTIs and ET used for 23 UTIs. At 7 days after start of treatment, questionnaire failure rate was 44% (20/45) for the CB group and 16% (3/19) for the ET group (P = 0.076). At 14 days following start of treatment, questionnaire failure rate was 31% (13/42) for the CB group and 17% (3/18) for the ET group (P = 0.3). In the ET group, 11% of cultures were found to be resistant to NF. CONCLUSION: Outcomes for the empiric treatment of uncomplicated UTI with NF at both 7 and 14 days are not significantly different than outcomes with culture-based treatment.

d-mannosuria levels measured 1 h after d-mannose intake can select out favorable responders: A pilot study.

BACKGROUND: d-mannose is used as preventive measure against recurrent urinary tract infections (RUTIs). We studied d-mannosuria after a challenge test to identify favorable responders that could be targeted for long-term preventive therapy. MATERIAL AND METHODS: Following institutional review board approval, women attending a specialized tertiary care center urology clinic with a history of RUTIs were invited to participate by providing a urine sample (baseline), followed by the intake of home-dose d-mannose, and a second urine sample 1 h later (post). Urine samples were processed according to a d-mannosuria assay technique reported previously by our group. d-mannose concentrations were normalized to urinary creatinine. RESULTS: From July 2020 to March 2021, 26 patients met study criteria. Thirteen had a lower or unchanged ratio of baseline to post d-mannose, whereas 13 were responders. Among 19 taking 2 g, 12 had a lower or unchanged trend and 7 were responders with >20% increase in the d-mannose/creatinine ratio. Comparison of urinary baseline d-mannose/creatinine ratios was significantly different between the responder (mean = 0.337 ± 0.158) and nonresponder (mean = 0.692 ± 0.444; p = 0.016) groups. Urinary post d-mannose/creatinine ratios did not significantly differ between the two groups (p = 0.46). d-mannose-naïve patients had few responders, and age and urinary creatinine did not affect the findings. CONCLUSION: This preliminary study on d-mannose challenge tests indicates a urine response if urinary d-mannose/creatinine ratio is low, which it was in some women with a history of RUTIs.

Electro-fulguration for extensive inflammatory bladder lesions in post-menopausal women with antibiotic-recalcitrant recurrent urinary tract infections.

INTRODUCTION AND HYPOTHESIS: To evaluate how women with uncomplicated antibiotic-recalcitrant recurrent urinary tract infections (RUTIs) and extensive inflammatory bladder lesions on office cystoscopy responded to electro-fulguration (EF) to eliminate these chronic bladder sites. METHODS: After IRB approval, a retrospective study of non-neurogenic women with RUTIs, inflammatory lesions on cystoscopy, and who underwent EF was performed. Lesions were classified through a simplified staging system based on the extent of bladder wall involvement. Only those with extensive bladder wall involvement (stages 3 and 4) at the time of EF were analyzed in this report. Six months after EF, an office cystoscopy was performed, with endoscopic success defined as no lesions seen. The primary clinical outcome was number of symptomatic UTIs after EF, defined as cure (0/year), improvement (1-2/year), and failure (≥3/year). RESULTS: From 2007 to 2019, a total of 57 women met the study criteria, 30 stage 3 and 27 stage 4. Nineteen (63%) were endoscopically successful in stage 3 and 11 (41%) in stage 4. Mean follow-up was 2.9 years (stage 3) and 3.1 years (stage 4). All had at least a 6-month UTI follow-up after the 6 months of office cystoscopy, with 15 patients cured, 37 improved, and 5 failed (all stage 4). CONCLUSIONS: Although EF only resulted in 63% complete endoscopic resolution, the majority experienced a decrease in the frequency of UTIs, suggesting that EF can be durably effective even in women with very extensive cystitis lesions.

A Deception Study to Avoid Recall Bias Confirms Similar Scores for 3 Validated Questionnaires in the Office or Over the Phone in Women With or Without Urinary Incontinence.

PURPOSE: With increasing telehealth technology, confirming the validity of non-office administration of questionnaires intended for office use only is important. We studied 3 validated questionnaires: the Urinary Distress Inventory 6-Short Form, the International Incontinence 7-Short Form, and a quality of life survey using a deception model. MATERIALS AND METHODS: Following Institutional Review Board approval and power calculations, these 3 questionnaires were prospectively administered in women with and without incontinence by phone and then again in person about 2 weeks later. To avoid recall bias, participants were not informed of the study over the phone. After completing their office visit questionnaire scores, they were told about the study and invited to consent for comparison of their phone and in-person questionnaire scores. Non-English speakers and those with an active urinary tract infection, with impaired mental competency, or on a fluid diet were excluded. RESULTS: From June to September 2021, 86 women, including 40 incontinent (30-85 years old) and 46 control (30-85 years old), with similar demographic parameters met all study criteria. Of the 14 questions studied, only 2, ie, Question 1 on the Urinary Distress Inventory 6-Short Form (P = .033) and Question 7 on the International Incontinence 7-Short Form (P = .036), showed rather minimal but statistically significant differences in scores. For incontinent women, only Question 7 on the International Incontinence 7-Short Form (P = .012) showed a significant score difference. CONCLUSIONS: The 3 questionnaire scores were overall comparable when obtained over the phone or during office visits. Women with incontinence, who may otherwise be lost to follow-up or only reachable by telehealth calls, can benefit from the remote administration of these 3 questionnaires.

Complement as Prognostic Biomarker and Potential Therapeutic Target in Renal Cell Carcinoma.

Preclinical studies demonstrated that complement promotes tumor growth. Therefore, we sought to determine the best target for complement-based therapy among common human malignancies. High expression of 11 complement genes was linked to unfavorable prognosis in renal cell carcinoma. Complement protein expression or deposition was observed mainly in stroma, leukocytes, and tumor vasculature, corresponding to a role of complement in regulating the tumor microenvironment. Complement abundance in tumors correlated with a high nuclear grade. Complement genes clustered within an aggressive inflammatory subtype of renal cancer characterized by poor prognosis, markers of T cell dysfunction, and alternatively activated macrophages. Plasma levels of complement proteins correlated with response to immune checkpoint inhibitors. Corroborating human data, complement deficiencies and blockade reduced tumor growth by enhancing antitumor immunity and seemingly reducing angiogenesis in a mouse model of kidney cancer resistant to PD-1 blockade. Overall, this study implicates complement in the immune landscape of renal cell carcinoma, and notwithstanding cohort size and preclinical model limitations, the data suggest that tumors resistant to immune checkpoint inhibitors might be suitable targets for complement-based therapy.

Targeting renal cell carcinoma with a HIF-2 antagonist.

Clear cell renal cell carcinoma (ccRCC) is characterized by inactivation of the von Hippel-Lindau tumour suppressor gene (VHL). Because no other gene is mutated as frequently in ccRCC and VHL mutations are truncal, VHL inactivation is regarded as the governing event. VHL loss activates the HIF-2 transcription factor, and constitutive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells. HIF-2 has been implicated in angiogenesis and multiple other processes, but angiogenesis is the main target of drugs such as the tyrosine kinase inhibitor sunitinib. HIF-2 has been regarded as undruggable. Here we use a tumourgraft/patient-derived xenograft platform to evaluate PT2399, a selective HIF-2 antagonist that was identified using a structure-based design approach. PT2399 dissociated HIF-2 (an obligatory heterodimer of HIF-2α-HIF-1ß) in human ccRCC cells and suppressed tumorigenesis in 56% (10 out of 18) of such lines. PT2399 had greater activity than sunitinib, was active in sunitinib-progressing tumours, and was better tolerated. Unexpectedly, some VHL-mutant ccRCCs were resistant to PT2399. Resistance occurred despite HIF-2 dissociation in tumours and evidence of Hif-2 inhibition in the mouse, as determined by suppression of circulating erythropoietin, a HIF-2 target and possible pharmacodynamic marker. We identified a HIF-2-dependent gene signature in sensitive tumours. Gene expression was largely unaffected by PT2399 in resistant tumours, illustrating the specificity of the drug. Sensitive tumours exhibited a distinguishing gene expression signature and generally higher levels of HIF-2α. Prolonged PT2399 treatment led to resistance. We identified binding site and second site suppressor mutations in HIF-2α and HIF-1ß, respectively. Both mutations preserved HIF-2 dimers despite treatment with PT2399. Finally, an extensively pretreated patient whose tumour had given rise to a sensitive tumourgraft showed disease control for more than 11 months when treated with a close analogue of PT2399, PT2385. We validate HIF-2 as a target in ccRCC, show that some ccRCCs are HIF-2 independent, and set the stage for biomarker-driven clinical trials.

Very long-term follow-up of autologous pubovaginal fascia slings in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to report on the very long-term outcome of a published series of autologous pubovaginal slings (PVS) in women with stress urinary incontinence (SUI). METHODS: Following institutional review board approval, a cohort of well characterized, non-neurogenic women who underwent an autologous PVS (primary [PVS1] and secondary [PVS2]) for SUI was re-evaluated for their very long-term outcome status. Data collected included demographics, validated questionnaires (Urogenital Distress Inventory - short form [UDI-6], Incontinence Impact Questionnaire - short form 7, quality of life), SUI retreatment/operations, and subjective patient-reported SUI improvement (%) and symptom recurrence. The primary outcome was success defined as UDI-6 question 3 (SUI) ≤ 1 and no SUI retreatment/operation. Patients not seen in clinic for 2 years were contacted via a standardized phone interview. RESULTS: From 83 patients with 7-year intermediate follow-up data, 34 (PVS1 = 18, PVS2 = 16) had very long-term follow-up based on clinic visit (7) or phone interviews (27). Those lost to follow-up (49), including 5 deceased, did not differ in demographics and intermediate outcomes from the followed cohort, but lived further away (>75 miles). At a mean age of 74 years, and with a median follow-up of 14.5 years, 53% met the success criteria (PVS1 = 44%, PVS2 = 63%). Mean postoperative questionnaire scores did not differ significantly between intermediate and very long-term follow-ups, and long-term outcomes between PVS1 and PVS2 remained similar. CONCLUSIONS: A majority of women with long-term follow-up after PVS for primary and secondary SUI remained successful more than 14 years after their surgery. Both groups, PVS1 and PVS2, fared equally well, confirming the durability of PVS as a treatment alternative for SUI.

Very long-term follow-up of the anterior vaginal wall suspension procedure for incontinence and/or prolapse repair.

OBJECTIVE: To report outcomes of the anterior vaginal wall suspension (AVWS) procedure for stress urinary incontinence (SUI) and/or anterior compartment prolapse (POP), with minimum 10-year follow-up. METHODS: Following institutional review board approval, a database of patients with > 10-year follow-up after AVWS for bothersome SUI with early stage anterior compartment prolapse (stage ≤ 2) or symptomatic anterior compartment prolapse (stage > 2) was reviewed. Preoperative evaluation included validated questionnaires [Urogenital Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), quality of life (QoL)], Pelvic Organ Prolapse Quantification (POP-Q), and voiding cystourethrography. Follow-up data was based on clinic visits or telephone interviews for patients not seen in the past 2 years. Telephone interviews used validated questionnaires and were conducted by a third party not involved in patient care. Failure was defined as reoperation for SUI or POP. The influence of lost to follow-up (LTF) was also analyzed. RESULTS: Between 1996 and 2008, 161 of 328 patients met study criteria, with follow-up from phone interviews (103) or clinic visits (58). The LTF patients were deceased (52), mentally disabled (5), or unreachable by telephone (110). Median follow-up was 13.5 years (IQR 11.5-17). Type of follow-up (clinic vs. phone) and uterine status (concomitant/prior/no hysterectomy) did not impact reoperation rates. Reoperation occurred in 23/161 (14%) and consisted of sacrocolpopexy (8), anterior colporrhaphy (5), injectable agents (8), fascial sling (2). CONCLUSIONS: The AVWS procedure to restore anterior vaginal support to the bladder neck and bladder base to correct SUI/POP can provide satisfactory and durable results.

Adverse effects of chronic nitrofurantoin therapy in women with recurrent urinary tract infections in an outpatient setting.

PURPOSE: To review the frequency of adverse events reported with nitrofurantoin (NF) in perimenopausal and menopausal women on prolonged daily prophylaxis in an outpatient setting. METHODS: Electronic medical records of women aged 50-95 prescribed NF by 2 primary urology providers for at least 3 consecutive months from 2006 to 2018 were retrospectively reviewed. Demographics, reason for the initiation, dose and duration of therapy, explanation of therapy interruptions, occurrence of adverse events, comorbid conditions, and relevant lab and imaging results were recorded. The number of months on prolonged therapy were summed. RESULTS: Of the 221 patients included, 167 (77%) were prescribed 100 mg of NF daily with a mean duration of therapy of 1.5 years. The most common indication for therapy was recurrent urinary tract infection prophylaxis. Breakthrough urinary tract infections developed in 88 (40%) patients on prolonged NF therapy but only 10 were not restarted on NF. Four patients (1.8%) were determined to have pulmonary adverse events and 1 (0.4%) developed elevated liver function tests. CONCLUSION: In peri-menopausal and menopausal women, the risks and benefits of chronic NF therapy should be weighed by the clinician and patient prior to prescribing long term NF. Patients must be educated about the potential NF toxicities and clinically monitored for signs and symptoms of potential adverse events while on chronic NF therapy.

Multidimensional outcomes of suburethral synthetic midurethral sling removal.

PURPOSE: To report multidimensional outcomes encompassing pain, dyspareunia, and recurrent urinary tract infections (UTIs), following suburethral sling removal (SSR) of synthetic midurethral slings (MUS) placed for female stress urinary incontinence. METHODS: We reviewed a prospectively maintained, IRB-approved database of women undergoing SSR at our institution. Demographic data, type of sling, and symptoms along with Urogenital Distress Inventory-Short Form (UDI-6) scores both before and after SSR were analyzed. Success was defined using several modalities including patient-reported symptoms (ideal outcome) and UDI-6 questionnaire. RESULTS: From 3/2006-2/2017, 443 women underwent SSR of which 230 met study criteria with median overall follow-up of 23 months (mean 30 months). 180/230 (78%) patients reported 3 or more symptoms at presentation. Median most recent post-SSR total UDI-6 score was 38 vs. 50 at baseline (p < 0.0001). By UDI-6, 53% of patients achieved success post-SSR. An ideal outcome was attained in 22/230 (10%) patients. A modified outcome allowing for one minimally invasive anti-incontinence procedure and excluding sexual activity classified 112/230 (49%) patients as successes. CONCLUSIONS: While patients with MUS present with multiple symptoms, following SSR, there is sustained improvement in multiple symptom domains, including pain and urinary incontinence. Allowing for minimally invasive anti-incontinence procedures (not inclusive of subsequent suburethral sling), the rate of success was 49%, which was comparable to that derived from UDI-6 scores (53%).

Predictors and outcomes of converted minimally invasive pancreaticoduodenectomy: a propensity score matched analysis.

BACKGROUND: Data-driven patient selection guidelines are not available to optimize outcomes in minimally invasive pancreaticoduodenectomy (MIPD). We aimed to define risk factors associated with conversion from MIPD to open PD and to determine the impact of conversion on post-operative outcomes. METHODS: We conducted a retrospective review of MIPD using NSQIP from 2014 to 2015. Propensity score was used to match patients who underwent completed MIPD to converted MIPD. RESULTS: 467 patients were included: 375 (80.3%) MIPD and 92 (19.7%) converted. Converted patients were more often male (64% vs. 52%, p = 0.030), had higher rates of dyspnea (10% vs. 3%, p = 0.009), underwent more vascular (44% vs. 14%, p < 0.001) or multivisceral resection (19% vs. 6%, p = 0.0005), and were more likely attempted laparoscopically compared to robotically (76% vs. 51%, p < 0.001). Robotic approach was independently associated with reduced risk of conversion (OR 0.40, 95% CI 0.23-0.69), while male gender (OR 1.70, 95% CI 1.02-2.84), history of dyspnea (OR 3.85, 95% CI 1.49-9.96), vascular resection (OR 4.32, 95% CI 2.53-7.37), and multivisceral resection (OR 2.18, 95% CI 1.05-4.52) were associated with increased risk. Major complications were more common in converted patients (68% vs. 37%, p < 0.001). Converted patients had increased odds of non-home discharge (OR 3.25, 95% CI 1.06-9.97) and an associated increased length of stay of 3 days (95% CI 0.1-6.7). CONCLUSION: Patients with a history of dyspnea or tumors requiring vascular or multivisceral resection were at increased risk of conversion, and the robotic platform was associated with a lower rate of conversion. Conversion was independently associated with increased overall complications, increased length of stay, and non-home discharge.

Long-Term Results of Burch and Autologous Sling Procedures for Stress Urinary Incontinence in E-SISTEr Participants at 1 Site.

PURPOSE: We report long-term outcomes in participants in the E-SISTEr (Extended Stress Incontinence Surgical Treatment Efficacy Trial) at 1 tertiary care center who underwent a Burch or a fascial sling procedure for stress urinary incontinence. MATERIALS AND METHODS: After receiving institutional review board approval E-SISTEr participants at 1 center who underwent midterm office evaluation in 2010 were further reevaluated at longer term followup by office visits and structured telephone interviews. The telephone interviews were performed by a third party not involved in patient care for those not seen in the last 2 years. Each group received validated questionnaires, including the UDI-6 (Urogenital Distress Inventory-Short Form), the IIQ-7 (Incontinence Impact Questionnaire-Short Form) and the visual analogue quality of life score questionnaire. Failure was measured by Kaplan-Meier curves using time to reoperation for stress urinary incontinence. RESULTS: Of the 29 eligible patients, including 14 treated with a Burch procedure and 15 treated with a sling procedure, 21 had long-term information available, including 11 and 10, respectively. Median followup was 15.1 years (range 11.2 to 16.0). One of the 8 patients was lost to followup, 1 died and 7 were unreachable by telephone. The UDI-6 question 3 score was lower for the 13 patients followed by telephone, including 13 and 7 with a Burch and a sling procedure compared to the 8 seen in clinic, including 5 and 3 with a Burch and a sling procedure, respectively (mean ± SD score 0.3 ± 0.6 vs 1.3 ± 1.1, p=0.0208). The UDI-6 scores were similar for the 2 procedures. Stress urinary incontinence reoperation was performed in 3 cases, including placement of a fascial sling in 1 Burch case. The other 2 cases in the Burch and sling groups received an injectable agent at 11.6 and 13.5 years, respectively. The overall Kaplan-Meier 15-year reoperation-free survival rate was 85.2% (95% CI 60.8-95). CONCLUSIONS: In this well characterized cohort with a median followup of 15.1 years there was sustained improvement in continence scores and quality of life related to stress urinary incontinence in each group and the reoperation rate was low.

Bethanechol: Is it still being prescribed for bladder dysfunction in women?

PURPOSE: Few medical treatment options exist for detrusor underactivity or urinary retention in women. Bethanechol, a cholinergic agonist, may improve detrusor contractility in these conditions; however, its clinical efficacy is limited. We sought to examine the patterns of Bethanechol use by physicians in an ambulatory care setting using a national database to determine if it is still prescribed for patients with bladder dysfunction. MATERIALS AND METHODS: The National Ambulatory Medical Care Survey (NAMCS) database was queried for a sample of patient visits to office-based physicians from 2003-2013. Visits were included for women aged 18 years or older with diagnosed lower urinary tract symptoms (LUTS), neurogenic bladder, or urinary retention based on ICD-9-CM codes. Visits in which Bethanechol was prescribed were analysed with descriptive statistics. Sampling weights were adjusted for nonresponders to yield an unbiased national estimate of ambulatory care visits. RESULTS: Out of a weighted sample of 17 321 630 included patient visits, 132 281 (0.8%) visits included a prescription for Bethanechol. Patients prescribed Bethanechol had a mean age of 62.3 ± 2.1 and were predominantly Caucasian (67%) followed by African American (18%). The primary diagnosis associated with Bethanechol was atony of bladder (35%), urinary retention (20%), neurogenic bladder (18%), urinary incontinence (16%), and incomplete bladder emptying (10%). Visits were primarily for chronic conditions (63%). It was typically prescribed as a continued medication (79%) most often by urologists (92%) followed by internal medicine clinicians (8%). CONCLUSIONS: Bethanechol continues to be prescribed in elderly women primarily for detrusor atony, urinary retention, or incomplete bladder emptying.

Macroplastique for women with stress urinary incontinence secondary to intrinsic sphincter deficiency.

OBJECTIVE: To evaluate the subjective and objective outcomes of MacroplastiqueR (MPQ) in women with stress urinary incontinence (SUI) secondary to intrinsic sphincter deficiency (ISD). MATERIALS AND METHODS: Following Institutional Review Board (IRB) approval, charts of non-neurogenic women with SUI secondary to ISD who underwent MPQ injection and had 6 months minimum follow-up were reviewed from a prospectively maintained database. Patients were divided into 3 groups: Naive (Group I), Prior Anti-Incontinence Surgery (Group II), and combined Prior Bulking Agent and Anti-Incontinence Surgery (Group III). Data collected included SUI self-report, Urogenital Distress Inventory (UDI-6) Question 3, and VAS Quality of Life (QoL) Questionnaire scores at baseline and in follow-up. Three-dimensional ultrasound (3DUS) evaluated volume/confi guration of MPQ. Success was defi ned after the last MPQ injection as a UDI-6 Question 3 score of 0 (dry) or 1, and no reoperation for SUI. RESULTS: From 2011-2017, 106 of 142 women met study criteria. At a median follow-up of 20 months (mean=26 months; range: 6-71), success rate was 41% for Group I, 40% for Group II, and 65% for Group III (p = 0.22). QoL scores were signifi cantly improved over baseline in all groups. There was no signifi cant difference in clinical outcome between the asymmetrical and symmetrical group on 3DUS. The completely dry rate was highest in Group III at 29%, compared to 4% for Group I and 15% for Group II (p = 0.05). CONCLUSION: MacroplastiqueR improved subjective and objective outcome measures for SUI secondary to ISD as both a primary and secondary treatment option in women.

Minimally Invasive Versus Open Pancreaticoduodenectomy: A Propensity-matched Study From a National Cohort of Patients.

OBJECTIVE: To compare the perioperative outcomes of minimally invasive pancreaticoduodenectomy (MIPD) in comparison with open pancreaticoduodenectomy (OPD) in a national cohort of patients. BACKGROUND: Limited well-controlled studies exist comparing perioperative outcomes between MIPD and OPD. METHODS: Patients who underwent MIPD and OPD were abstracted from the 2014 to 2015 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program. OPD and MIPD patients were matched 3:1 using propensity score, and perioperative outcomes were compared. RESULTS: A total of 4484 patients were identified with 334 (7.4%) undergoing MIPD. MIPD patients were younger, more likely to be White, and had a lower rate of weight loss. They were more likely to undergo classic Whipple and to have a drain placed. After 3:1 matching, 1002 OPD patients were compared with 334 MIPD patients. MIPD was associated with longer mean operative time (426.6 vs 359.6 minutes; P < 0.01), higher readmission rate (19.2% vs 14.3%; P = 0.04) and lower rate of prolonged length of stay >14 days (16.5% vs 21.6%; P = 0.047). The 2 groups had a similar rate of 30-day mortality (MIPD 1.8% vs OPD 1.3%; P = 0.51), overall complications, postoperative pancreatic fistula, and delayed gastric emptying. A secondary analysis comparing MIPD without conversion or open assist with OPD showed that MIPD patients had lower rates of overall surgical site infection (13.4% vs 19.6%; P = 0.04) and transfusion (7.9% vs 14.4%; P = 0.02). CONCLUSIONS: MIPD had an equivalent morbidity and mortality rate to OPD, with the benefit of a decreased rate of prolonged length of stay, though this is partially offset by an increased readmission rate.

Challenges of Multidimensional Outcome Reporting after Suburethral Mid Urethral Sling Removal.

PURPOSE: We sought to determine the types and frequency of presenting symptoms in women undergoing suburethral mid urethral sling removal to improve outcome reporting after removal. MATERIALS AND METHODS: Following institutional review board approval women who underwent suburethral mid urethral sling removal of 1 mid urethral sling were evaluated for their presenting symptoms and correlation with the UDI-6 (Urogenital Distress Inventory-Short Form) questionnaire. Demographic data were recorded. Patient reported presenting symptoms were categorized into 5 domains, including storage symptoms, voiding symptoms, pain, recurrent urinary tract infections or urinary incontinence. The UDI-6 was reviewed preoperatively and 6 to 12 months postoperatively. We also calculated an ideal outcome, defined as resolution of incontinence, pain, resumption of sexual activity and no need for further anti-incontinence procedures. RESULTS: A total of 230 women from 2006 to 2017 met study inclusion criteria, including 116 who completed the UDI-6 postoperatively. Of the women 80% had 3 or more presenting symptoms with pain as the most common symptom. The most common combination of symptoms was all 5 domains, which was noted in 46 of the 230 women (20%). An increasing number of symptoms correlated with the total preoperative UDI-6 score. Symptom domains were associated with the corresponding UDI-6 subdomain questions. Domains not covered by the UDI-6, ie recurrent urinary tract infections and dyspareunia, accounted for 27% of reported symptoms. Due to limited data on sexual activity an ideal outcome was reached in 10% of patients but this rate was 40% after sexual activity information was excluded. CONCLUSIONS: In this series the presenting symptoms were manifold in women undergoing suburethral mid urethral sling removal. The UDI-6 questionnaire correlated with many of these complaints. It may be used in outcome analysis in conjunction with self-reported symptoms.