Ubiquitination regulates ER-phagy and remodelling of endoplasmic reticulum.

The endoplasmic reticulum (ER) undergoes continuous remodelling via a selective autophagy pathway, known as ER-phagy1. ER-phagy receptors have a central role in this process2, but the regulatory mechanism remains largely unknown. Here we report that ubiquitination of the ER-phagy receptor FAM134B within its reticulon homology domain (RHD) promotes receptor clustering and binding to lipidated LC3B, thereby stimulating ER-phagy. Molecular dynamics (MD) simulations showed how ubiquitination perturbs the RHD structure in model bilayers and enhances membrane curvature induction. Ubiquitin molecules on RHDs mediate interactions between neighbouring RHDs to form dense receptor clusters that facilitate the large-scale remodelling of lipid bilayers. Membrane remodelling was reconstituted in vitro with liposomes and ubiquitinated FAM134B. Using super-resolution microscopy, we discovered FAM134B nanoclusters and microclusters in cells. Quantitative image analysis revealed a ubiquitin-mediated increase in FAM134B oligomerization and cluster size. We found that the E3 ligase AMFR, within multimeric ER-phagy receptor clusters, catalyses FAM134B ubiquitination and regulates the dynamic flux of ER-phagy. Our results show that ubiquitination enhances RHD functions via receptor clustering, facilitates ER-phagy and controls ER remodelling in response to cellular demands.

Self-quenched Fluorophore Dimers for DNA-PAINT and STED Microscopy.

Super-resolution techniques like single-molecule localisation microscopy (SMLM) and stimulated emission depletion (STED) microscopy have been extended by the use of non-covalent, weak affinity-based transient labelling systems. DNA-based hybrid systems are a prominent example among these transient labelling systems, offering excellent opportunities for multi-target fluorescence imaging. However, these techniques suffer from higher background relative to covalently bound fluorophores, originating from unbound fluorophore-labelled single-stranded oligonucleotides. Here, we introduce short-distance self-quenching in fluorophore dimers as an efficient mechanism to reduce background fluorescence signal, while at the same time increasing the photon budget in the bound state by almost 2-fold. We characterise the optical and thermodynamic properties of fluorophore-dimer single-stranded DNA, and show super-resolution imaging applications with STED and SMLM with increased spatial resolution and reduced background.

Evaluating the Safety of Active Surveillance: Outcomes of Deferred Radical Prostatectomy after an Initial Period of Surveillance.

PURPOSE: As enrollment in active surveillance expands, it is increasingly important to assess the potential risks of deferred treatment. We evaluated the risk of prostate specific antigen recurrence in a large cohort of men who underwent radical prostatectomy after initial active surveillance. MATERIALS AND METHODS: The study included men who underwent radical prostatectomy after a period of active surveillance. At diagnosis the men had GG (Gleason Grade Group) 1 or 2, clinical T2 or less and low or intermediate risk disease. They were stratified by a composite variable of GG and the volume of high grade cores at diagnosis. Pathological characteristics and recurrence after radical prostatectomy were evaluated. RESULTS: Of 1,916 men enrolled in active surveillance between 1994 and 2017, 448 (23.4%) underwent deferred radical prostatectomy. Median time to radical prostatectomy was 27 months (IQR 15.5-46.5). At diagnosis 388 men (86.6%) had GG1 disease, 31 (6.9%) had GG2 disease with 1 high grade core and 29 (6.5%) had GG2 disease with 2 or more high grade cores. GG2 with 2 or more high grade cores at diagnosis was associated with an increased risk of recurrence compared to GG1 disease (HR 3.29, 95% CI 1.49-7.26, p <0.01). GG2 disease with 1 high grade core did not significantly differ from GG1. CONCLUSIONS: Our results support the careful use of active surveillance in men with GG2 and 1 high grade core at diagnosis. Men with 2 or more high grade (GG2 or greater) cores at diagnosis may benefit from immediate treatment.

Minority Recruitment Trends in Phase III Prostate Cancer Clinical Trials (2003 to 2014): Progress and Critical Areas for Improvement.

PURPOSE: American minority groups have been historically underrepresented in phase III prostate cancer clinical trials despite often having higher risk disease. We analyzed enrollment trends of major racial/ethnic groups in the United States in phase III prostate cancer trials between 2003 and 2014 compared to SEER (Surveillance, Epidemiology and End Results) incidence data. MATERIALS AND METHODS: Phase III prostate cancer trials primarily enrolling patients from the United States were identified in the ClinicalTrials.gov database. Enrollment trends were analyzed for major racial/ethnic groups. Prostate cancer incidence data from the SEER registry were used to identify enrollment targets. The enrollment difference was determined by calculating the absolute difference between the percent of a racial/ethnic subgroup in the SEER registry population and the percent of that subgroup in the phase III prostate cancer trial population. RESULTS: Among 39 studies identified African American enrollment in therapeutic trials increased across the study period (p <0.001). The enrollment difference for African Americans was -9.0% (95% CI -7.6- -10.5, p <0.001) in 2003 to 2005 and 1.4% (95% CI 0.2-2.6, p = 0.020) in 2012 to 2014. However, African American men were under enrolled in metastatic disease trials (enrollment difference -5.8%, 95% CI -4.8- -6.8, p <0.001). Latino and Asian American men were consistently under enrolled in all trial types. CONCLUSIONS: Minority groups in the United States were largely under enrolled in phase III prostate cancer trials between 2003 and 2014. While recruitment efforts may have had an impact, as demonstrated by increased enrollment of African American men, there remains a need to expand recruitment efforts to achieve diversity in trials.

The association of bicycle-related genital numbness and Sexual Health Inventory for Men (SHIM) score: results from a large, multinational, cross-sectional study.

OBJECTIVE: To assess the association of genital numbness and erectile dysfunction in male cyclists. SUBJECTS AND METHODS: Cyclists were recruited through Facebook advertisements and outreach to sporting clubs. This is a secondary analysis of a larger epidemiological population-based study that examined sexual and urinary wellness in athletes. We queried cycling habits and erectile function using Sexual Health Inventory for Men (SHIM). RESULTS: A total of 2 774 male cyclists were included in the analysis. Amongst cyclists, there was a statistically significant increase in the trend of genital numbness presence with more years of cycling (P = 0.002), more frequent weekly cycling (P < 0.001), and longer cycling distance at each ride (P < 0.001). Less frequent use of padded shorts (odds ratio [OR] 0.14, P < 0.001) and lower handlebar (OR 0.49, P < 0.001) were associated with numbness, but body mass index (BMI) (OR 1.1, P = 0.33) and age (OR 1.2, P = 0.15) were not. In a multivariate logistic regression model, after adjusting for age, BMI, and lifetime miles (calculated by average daily cycling mileage × cycling days/week × cycling years.), there were no statistically significant differences in mean SHIM score between cyclists with and cyclists without numbness (20.3 vs 20.2, P = 0.83). However, interestingly, the subset of cyclists who reported numbness in the buttock reported statistically significantly worse SHIM scores (20.3 vs 18.4, P < 0.001). This association was not present in cyclists who reported numbness in the scrotum, penis, or perineum and remained significant after adjusting for overall biking intensity. CONCLUSION: Cyclists report genital numbness in proportion with biking intensity but numbness is not associated with worse sexual function in this cohort.

A Mobile Health Intervention for Prostate Biopsy Patients Reduces Appointment Cancellations: Cohort Study.

BACKGROUND: Inadequate patient education and preparation for office-based procedures often leads to delayed care, poor patient satisfaction, and increased costs to the health care system. We developed and deployed a mobile health (mHealth) reminder and education program for patients scheduled for transrectal prostate biopsy. OBJECTIVE: We aimed to evaluate the impact of an mHealth reminder and education program on appointment cancellation rates, communication frequency, and patient satisfaction. METHODS: We developed a text message (SMS, short message service)-based program with seven reminders containing links to Web-based content and surveys sent over an 18-day period (14 days before through 3 days after prostate biopsy). Messages contained educational content, reminders, and readiness questionnaires. Demographic information, appointment cancellations or change data, and patient/provider communication events were collected for 6 months before and after launching the intervention. Patient satisfaction was evaluated in the postintervention cohort. RESULTS: The preintervention (n=473) and postintervention (n=359) cohorts were composed of men of similar median age and racial/ethnic distribution living a similar distance from clinic. The postintervention cohort had significantly fewer canceled or rescheduled appointments (33.8% vs 21.2%, P<.001) and fewer same-day cancellations (3.8% vs 0.5%, P<.001). There was a significant increase in preprocedural telephone calls (0.6 vs 0.8 calls per patient, P=.02) in the postintervention cohort, but not a detectable change in postprocedural calls. The mean satisfaction with the program was 4.5 out of 5 (SD 0.9). CONCLUSIONS: An mHealth periprocedural outreach program significantly lowered appointment cancellation and rescheduling and was associated with high patient satisfaction scores with a slight increase in preprocedural telephone calls. This led to fewer underused procedure appointments and high patient satisfaction.

Self-Quenched Fluorophore-DNA Labels for Super-Resolution Fluorescence Microscopy.

Protein labeling through transient and repetitive hybridization of short, fluorophore-labeled DNA oligonucleotides has become widely applied in various optical super-resolution microscopy methods. The main advantages are multitarget imaging and molecular quantification. A challenge is the high background signal originating from the presence of unbound fluorophore-DNA labels in solution. Here, we report the self-quenching of fluorophore dimers conjugated to DNA oligonucleotides as a general concept to reduce the fluorescence background. Upon hybridization, the fluorescence signals of both fluorophores are restored. We expand the toolbox of fluorophores suitable for self-quenching and report their spectra and hybridization equilibria. We apply self-quenched fluorophore-DNA labels to stimulated emission depletion microscopy and single-molecule localization microscopy and report improved imaging performances.

Limited Relevance of the Very Low Risk Prostate Cancer Classification in the Modern Era: Results from a Large Institutional Active Surveillance Cohort.

Although the American Urological Association recently dropped the very low-risk (VLR) subcategory for low-risk prostate cancer (PCa) and the European Association of Urology does not substratify low-risk PCa, the National Comprehensive Cancer Network (NCCN) guidelines still maintain this stratum, which is based on the number of positive biopsy cores, tumor extent in each core, and prostate-specific antigen density. This subdivision may be less applicable in the modern era in which imaging-targeted prostate biopsies are common practice. In our large institutional active surveillance cohort of patients diagnosed from 2000 to 2020 (n = 1276), the number of patients meeting NCCN VLR criteria decreased significantly in recent years, with no patient meeting VLR criteria after 2018. By contrast, the multivariable Cancer of the Prostate Risk Assessment (CAPRA) score effectively substratified patients over the same period and was predictive of upgrading on repeat biopsy to Gleason grade group ≥2 on multivariable Cox proportional-hazards regression modeling (hazard ratio 1.21, 95% confidence interval 1.05-1.39; p < 0.01), independent of age, genomic test results, and magnetic resonance imaging findings. These findings suggest that the NCCN VLR criteria are less applicable in the targeted biopsy era, and that the CAPRA score or similar instruments are better contemporary risk stratification tools for men on active surveillance. PATIENT SUMMARY: We investigated whether the National Comprehensive Cancer Network classification of very low risk (VLR) for prostate cancer is relevant in the modern era. We found that in a large group of patients on active surveillance, no man diagnosed after 2018 satisfied the VLR criteria. However, the Cancer of the Prostate Risk Assessment (CAPRA) score discriminated patients by cancer risk at diagnosis and was predictive of outcomes on active surveillance, and thus may be a more relevant classification scheme in the modern era.

The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways.

Selective autophagy of the endoplasmic reticulum (ER), known as ER-phagy, is an important regulator of ER remodeling and essential to maintain cellular homeostasis during environmental changes. We recently showed that members of the FAM134 family play a critical role during stress-induced ER-phagy. However, the mechanisms on how they are activated remain largely unknown. In this study, we analyze phosphorylation of FAM134 as a trigger of FAM134-driven ER-phagy upon mTOR (mechanistic target of rapamycin) inhibition. An unbiased screen of kinase inhibitors reveals CK2 to be essential for FAM134B- and FAM134C-driven ER-phagy after mTOR inhibition. Furthermore, we provide evidence that ER-phagy receptors are regulated by ubiquitination events and that treatment with E1 inhibitor suppresses Torin1-induced ER-phagy flux. Using super-resolution microscopy, we show that CK2 activity is essential for the formation of high-density FAM134B and FAM134C clusters. In addition, dense clustering of FAM134B and FAM134C requires phosphorylation-dependent ubiquitination of FAM134B and FAM134C. Treatment with the CK2 inhibitor SGC-CK2-1 or mutation of FAM134B and FAM134C phosphosites prevents ubiquitination of FAM134 proteins, formation of high-density clusters, as well as Torin1-induced ER-phagy flux. Therefore, we propose that CK2-dependent phosphorylation of ER-phagy receptors precedes ubiquitin-dependent activation of ER-phagy flux.

Patient engagement in a mobile health intervention to improve preparedness for prostate biopsy.

OBJECTIVE: We designed and implemented a peri-procedural text message (SMS) program for patients undergoing transrectal prostate biopsy and aimed to evaluate predictors of patient enrollment and engagement with the SMS program. METHODS: We designed an SMS-based program with 8 messages containing web-based modules with educational content and reminders confirming MRI for fusion biopsy, antibiotic adherence, enema use, and anticoagulation cessation. Data on patient demographics, enrollment, and engagement with modules were collected from June 1, 2018 to February 28, 2021. Engagement was defined as a patient clicking a link delivered via SMS to access modules. We made multivariable models to identify predictors of patient enrollment and engagement. RESULTS: Of the 1,760 prostate biopsies between June 2018 and March 2021, 1,383 (78.6%) were enrolled in SMS, 182 (10.3%) in email, 106 (6.0%) in both, and 240 (13.6%) were not enrolled. Of 1418 patients enrolled, 1,270 (89.6%) engaged with at least one module. African American patients had 50% lower odds of being enrolled (OR = 0.50, 95% CI 0.28-0.96; P = 0.03), but once enrolled there were no differences in engagement. Patients for whom English was not listed as their primary language had 60% lower odds of engagement (OR = 0.40, 95% CI 0.17-1.00, P = .04) and patients who were single or divorced had a 40% lower odds of engagement (OR = 0.60, 95% CI 0.41-0.91, P = 0.01). CONCLUSIONS: A cohort of older men undergoing prostate biopsy were able to engage with a text message-based education and reminder program. Future efforts must address barriers to enrollment for Black or African American men and improve accessibility to non-English speaking patients.

Unraveling the hidden temporal range of fast ß2-adrenergic receptor mobility by time-resolved fluorescence.

G-protein-coupled receptors (GPCRs) are hypothesized to possess molecular mobility over a wide temporal range. Until now the temporal range has not been fully accessible due to the crucially limited temporal range of available methods. This in turn, may lead relevant dynamic constants to remain masked. Here, we expand this dynamic range by combining fluorescent techniques using a spot confocal setup. We decipher mobility constants of ß2-adrenergic receptor over a wide time range (nanosecond to second). Particularly, a translational mobility (10 µm²/s), one order of magnitude faster than membrane associated lateral mobility that explains membrane protein turnover and suggests a wider picture of the GPCR availability on the plasma membrane. And a so far elusive rotational mobility (1-200 µs) which depicts a previously overlooked dynamic component that, despite all complexity, behaves largely as predicted by the Saffman-Delbrück model.

Synergizing Exchangeable Fluorophore Labels for Multitarget STED Microscopy.

Investigating the interplay of cellular proteins with optical microscopy requires multitarget labeling. Spectral multiplexing using high-affinity or covalent labels is limited in the number of fluorophores that can be discriminated in a single imaging experiment. Advanced microscopy methods such as STED microscopy additionally demand balanced excitation, depletion, and emission wavelengths for all fluorophores, further reducing multiplexing capabilities. Noncovalent, weak-affinity labels bypass this "spectral barrier" through label exchange and sequential imaging of different targets. Here, we combine exchangeable HaloTag ligands, weak-affinity DNA hybridization, and hydrophophic and protein-peptide interactions to increase labeling flexibility and demonstrate six-target STED microscopy in single cells. We further show that exchangeable labels reduce photobleaching as well as facilitate long acquisition times and multicolor live-cell and high-fidelity 3D STED microscopy. The synergy of different types of exchangeable labels increases the multiplexing capabilities in fluorescence microscopy, and by that, the information content of microscopy images.

Formal Mentorship as an Opportunity to Expand the Urology Pipeline: Under Represented Trainees Entering Residency (UReTER) Program Evaluation 2020-2021.

OBJECTIVE: To rank percentages of underrepresented residents in surgical subspecialties and understand the experience of mentees and mentors who participated in the inaugural University of California, San Francisco Urology UnderRepresented Trainees Entering Residency (UReTER) Mentorship Program for Black, Indigenous, and/or LatinX medical students applying into urology. METHODS: Medical student mentees across the country were recruited via social media and email listservs. Demographic information and photos of mentors were presented on the UReTER website. Medical students could choose a mentor, and once matched, both parties were notified. A survey was emailed to all participants on Urology Match Day 2021. RESULT: The 2018 -2019 ACGME Databook showed underrepresented minority residents made up 7.6% of urology residents, lagging behind neurosurgery, vascular surgery, general surgery, and obstetrics and gynecology. 71 mentees and 101 mentors volunteered for the UReTER Mentorship Program (71 mentor-mentee couplets). Overall response rate was 51% [33 mentors and 32 mentees]. Of mentees who completed the survey, 16 (47%) participated in the 2021 Urology Match; 15 (94%) matched and 6 (38%) felt that UReTER helped them match. CONCLUSION: Feedback on this pilot program was very positive including a high match rate among those who participated. Future changes to the program include expanded student outreach, increased structure, broadened mentor network. The implementation of a low-cost program to increase underrepresented applicants into Urology has great potential to increase representation and improve the field. This program can and should be replicated in all subspecialties.

Medium Term Outcomes of Focal Cryoablation for Intermediate and High Risk Prostate Cancer: MRI and PSA are Not Predictive of Residual or Recurrent Disease.

OBJECTIVE: To understand oncologic outcomes of focal cryoablation for prostate cancer and efficacy MRI and PSA to predict residual disease and recurrence. METHODS: We retrospectively analyzed patients who underwent focal cryotherapy at a single institution. Inclusion criteria included clinically localized biopsy-proven cancer that was clearly visible on MRI or ultrasound. The primary outcomes were failure-free survival (FFS) defined as no transition to radical, whole-gland or systemic therapy and biochemical recurrence (Phoenix PSA nadir +2 increases), and secondary outcomes included changes in the Gleason grade group (GG) and MRI findings. RESULTS: 75 patients completed post cryotherapy biopsy with a median follow-up of 1.89 [IQR 1.19-2.77] years. Failure free survival was met by 96.2% of patients at 2 year follow up and of those who did not meet this outcome, 3 had metastasis, 1 had a salvage prostatectomy and 5 underwent radiation. On the treated side of the prostate, 7 (9.5%) of patients had residual ≥GG2 disease compared to 7 (9.5%) patients on the untreated side. Out of the 12 patients who had residual ≥GG2 disease at follow up biopsy (either on treated or untreated side of the prostate), 11 (91.7%) had PI-RADS 1-3 on follow up MRI. Using a multivariate cox proportional hazards model, Phoenix criteria for recurrence (PSA nadir +2) was not predictive for FFS. CONCLUSIONS: Focal cryotherapy is effective for treating focal lesions of prostate cancer, but patients require continued surveillance. MRI and PSA are not reflective of residual disease on follow up biopsy.

Evaluating the impact of surgical supply cost variation during partial nephrectomy on patient outcomes.

BACKGROUND: Reducing surgical supply costs can help to lower hospital expenditures. We aimed to evaluate whether variation in supply costs between urologic surgeons performing both robotic or open partial nephrectomies is associated with differential patient outcomes. METHODS: In this retrospective cohort study, we reviewed 399 consecutive robotic (n=220) and open (n=179) partial nephrectomies performed at an academic center. Surgical supply costs were determined at the institution-negotiated rate. Through retrospective review, we identified factors related to case complexity, patient comorbidity, and perioperative outcomes. Two radiologists assigned nephrometry scores to grade tumor complexity. We created univariate and multivariable models for predictors of supply costs, length of stay, and change in serum creatinine. RESULTS: Median supply cost was $3,201 [interquartile range (IQR): $2,201-3,808] for robotic partial nephrectomy and $968 (IQR: $819-1,772) for open partial nephrectomy. Mean nephrometry score was 7.0 (SD =1.7) for robotic procedures and 8.2 (SD =1.6) for open procedures. In multivariable models, the surgeon was the primary significant predictor of variation in surgical supply costs for both procedure types. In multivariable mixed-effects analysis with surgeon as a random effect, supply cost was not a significant predictor of change in serum creatinine for robotic or open procedures. Supply cost was not a statistically significant predictor of length of stay for the open procedure. Supply cost was a significant predictor of longer length of stay for the robotic procedure, however it was not a clinically meaningful change in length of stay (0.02 days per $100 in supply costs). CONCLUSIONS: Higher supply spending did not predict significantly improved patient outcomes. Variability in surgeon supply preference is the likely source of variability in supply cost. These data suggest that efforts to promote cost-effective utilization and standardization of supplies in partial nephrectomy could help reduce costs without harming patients.

"Can you hear me now?": postoperative patient-initiated communication with providers.

OBJECTIVES: Surgical patients often leave the hospital with many questions and concerns after their surgery and will contact their providers to get answers. The growth of patient-provider communication (PPC) technologies allows for many new opportunities to study postoperative patient-initiated communication. We aimed to characterize a growing body of literature on postoperative patient-initiated communication. STUDY DESIGN: Review. METHODS: A scoping review methodology was used to identify 17 studies analyzing patient-initiated communication in the postoperative period and to characterize key results and areas of investigation in the literature. Patient-initiated communication in the postoperative period was defined as any communication initiated by the patient after discharge. RESULTS: The majority of studies were published between 2014 and 2018 (82.4%). Telephone calls were the most common type of medium investigated (11 studies; 64.7%), followed by secure messaging (2 studies; 11.8%). Patients most commonly initiated contact regarding study results, medications, and wounds. Common areas of investigation included communication timing and sociodemographic associations. CONCLUSIONS: As health systems adopt new technologies for PPC, understanding how and why patients initiate contact with providers postoperatively can inform efforts to strengthen PPC broadly. Moreover, research on sociodemographic variation in communication patterns after surgery can help address communication gaps that patient groups may experience. Future research can build upon this work to improve patient outcomes and increase clinic efficiency.

Determinants of Guideline-Based Treatment in Patients With cT1 Bladder Cancer.

INTRODUCTION: Clinical T1 (cT1) bladder cancer is associated with high rates of recurrence, upstaging, and progression. Guidelines recommend that these patients be treated with adjuvant intravesical Bacillus Calmette-Guérin immunotherapy (BCG) or upfront radical cystectomy (RC). We analyzed the National Cancer Database (NCDB) to identify demographic and clinical determinants of guideline-based treatment (GBT) and RC. PATIENTS AND METHODS: We identified 47,694 patients in the NCDB with cT1 bladder cancer diagnosed in 2004-2013. Those who did not receive any treatment or underwent primary chemotherapy were excluded. Mixed effects logistic regression adjusted for facility-level variation was used to identify factors associated with receipt of GBT. RESULTS: The median age of the cohort was 72 years (interquartile range, 63-79). Of the patients, 22.4% were female, 5.1% were African American, and 2.7% had variant histology. Nearly one-third of patients received GBT: 11,453 (24%) were initially treated with BCG and 3320 (7%) were initially treated with RC. Recent year of diagnosis (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.52-1.85; P < .001), treatment at an academic center (OR, 2.42; 95% CI, 2.27-2.59; P < .001), and private insurance status (OR, 1.41; 95% CI, 1.19-1.66; P < .001) were associated with increased odds of GBT. Of patients who received GBT, variant histology (OR, 5.89; 95% CI, 4.65-7.47; P < .001), and recent year of diagnosis (OR, 1.89; 95% CI, 1.50-2.39; P < .001) were associated with greater odds of RC. CONCLUSION: There is low treatment-guideline compliance for patients with cT1 disease. However, there appears to be a temporal trend toward increased use of GBT. Efforts should be made to understand why many cT1 bladder cancer patients do not receive GBT.

Trends and Predictors of Adjuvant Therapy for Adverse Features Following Radical Prostatectomy: An Analysis From Cancer of the Prostate Strategic Urologic Research Endeavor.

OBJECTIVE: To determine trends and predictors of adjuvant therapy in patients with adverse features at radical prostatectomy (RP), and to investigate the associations of adjuvant therapy and adverse feature type with survival. METHODS: From the Cancer of the Prostate Strategic Urologic Research Endeavor registry (1990-2017), 2209 men with adverse features (pT3N0M0 disease and/or positive surgical margins), and 108 men with positive lymph nodes (pN1) at RP were identified. Temporal trends were evaluated, and predictors of adjuvant therapy were assessed with multivariate logistic regression. Kaplan-Meier analysis and competing risks regression were used to test cumulative incidence and risk of all-cause and prostate cancer-specific mortality. RESULTS: Of 2209 men with adverse features and pN0 disease, 89 (4.0%), 82 (3.7%), and 30 (1.4%) received adjuvant external beam radiation therapy (ERBT) alone, androgen deprivation therapy (ADT) alone, or combined EBRT and ADT, respectively. Of 108 men with pN1 disease, 54 (50%) received ADT with or without EBRT. Adjuvant treatment for patients with adverse features decreased from 13.3% (1990-1994) to 6% or less (2005-2017, Ptrend <.001). Patients with margin positive pT3a (odds ratio 4.13; 95% confidence interval 2.21-7.73; P<.01) and margin positive pT3b disease (odds ratio 7.09; 95% confidence interval 3.66-1.73; P<.01) had greater odds of receiving adjuvant therapy compared to patients with margin negative pT3a disease. Adverse feature type was associated with prostate cancer-specific mortality in univariate analysis (log-rank P <.01), but not in competing risks regression (P= .06). CONCLUSION: Adjuvant therapy declined for men with adverse features at RP. Providers do not treat all adverse feature types the same way, despite broad treatment recommendations in guidelines.

Surgical Management of Post-Esophagectomy Tracheo-Bronchial-Esophageal Fistula.

BACKGROUND: Post-esophagectomy tracheo-bronchial-esophageal fistula (PETEF) most often develops after anastomotic disruption or gastric conduit necrosis. Ideal surgical management and outcomes for this complication are uncertain. METHODS: A retrospective review of 11 patients undergoing surgical repair of PETEF was performed. RESULTS: The median time between esophagectomy and surgical repair of PETEF was 61 days (range, 7 days to 28 years). Anastomotic leak or gastric conduit necrosis was responsible for PETEF in 6 patients (54.5%), whereas other causes were erosion of a tracheal appliance (n = 2), gastric conduit staple line erosion (n = 1), anastomotic stricture dilation (n = 1), and recurrent esophageal cancer (n = 1). Membranous airway defects were repaired primarily and buttressed with muscle or omental flaps in 8 patients (72.7%), whereas two (18.2%) were repaired with bio-prosthetic patches and one (9.1%) was repaired with a sleeve resection of the bronchus. Anastomotic and neo-esophageal conduit defects were repaired primarily in 3 patients (27.3%), whereas 7 patients (63.6%) underwent conduit take-down and esophageal or pharyngeal diversion, and 1 patient (9.1%) underwent simultaneous fistula repair and colon interposition. Two patients (18.2%) had recurrent fistulas, with 1 patient dying after second fistula closure and the other was discharged with no further attempt at repair. Three patients (27.3%) died postoperatively. Only 3 patients (27.3%) resumed an oral diet after fistula repair. CONCLUSIONS: Surgical treatment is effective for most patients undergoing operative repair of PETEF, notwithstanding a considerable risk of postoperative morbidity and death. Although fistula repair is life saving and prevents further respiratory deterioration, return to oral alimentation is not ensured.

Genital burns in the United States: Disproportionate prevalence in the pediatric population.

INTRODUCTION AND OBJECTIVES: To describe the epidemiology of genital burns in the U.S. and investigate the underlying etiology. METHODS: The National Electronic Injury Surveillance System database was queried for individuals who sustained genital burns from 2000 to 2016. We collected data on age, gender, injury diagnosis, disposition, and causative agents. Multivariate analysis was performed to determine predictors of hospitalization. RESULTS: We estimate 17,026 (95% CI 16,649-17,404) cases of genital burns presented to emergency departments nationally. Genital burns occurred more in males than females (12,295 vs 4,731). Scalding (57.9%) was the most common mechanism of injury and hot water (35.7%) the most common causative agent. Significant predictors of hospitalization on multivariate analysis were multi-surface (OR 4.4), scalding (OR 11.5) and thermal burns (OR 27.9). Children ages 0-2 had the highest prevalence of genital burns, and children ages 0-12 comprised 37.1% of the study. For children <5years of age, majority of the burns were caused by hot water in the bathroom. In age group 6-12, the most common causes of genital burns were cooking-related scalds due to hot foods and water. CONCLUSIONS: Children sustain genital burns at a higher rate than adults and many appear to have a preventable mechanism. Improved product design for safety and educating caregivers about potential hazardous situations are needed.