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Objective: To evaluate longitudinal trends in surgical case volume among junior urology residents. There is growing perception that urology residents are not prepared for independent practice, which may be linked to decreased exposure to major cases early in residency., Methods: Retrospective review of deidentified case logs from urology residency graduates from 12 academic medical centers in the United States from 2010 to 2017. The primary outcome was the change in major case volume for first-year urology (URO1) residents (after surgery internship), measured using negative binomial regression., Results: A total of 391,399 total cases were logged by 244 residency graduates. Residents performed a median of 509 major cases, 487 minor cases, and 503 endoscopic cases. From 2010 to 2017, the median number of major cases performed by URO1 residents decreased from 64 to 49 (annual incidence rate ratio 0.90, P < .001). This trend was limited to oncology cases, with no change in reconstructive or pediatric cases. The number of major cases decreased more for URO1 residents than for residents at other levels (P-values for interaction <.05). The median number of endoscopic cases performed by URO1 residents increased from 85 to 194 (annual incidence rate ratio 1.09, P < .001), which was also disproportionate to other levels of residency (P-values for interaction <.05)., Conclusion: There has been a shift in case distribution among URO1 residents, with progressively less exposure to major cases and an increased focus on endoscopic surgery. Further investigation is needed to determine if this trend has implications on the surgical proficiency of residency graduates., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance. Phylogenetic analysis confirms that in all cases the urothelial and squamous regions are derived from a common shared precursor. Despite the presence of marked genomic heterogeneity between co-existent urothelial and squamous differentiated regions, no recurrent genomic alteration exclusive to the urothelial or squamous morphologies is identified. Rather, lineage plasticity in bladder cancers with squamous differentiation is associated with loss of expression of FOXA1, GATA3, and PPARG, transcription factors critical for maintenance of urothelial cell identity. Of clinical significance, lineage plasticity and PD-L1 expression is coordinately dysregulated via FOXA1, with patients exhibiting morphologic heterogeneity pre-treatment significantly less likely to respond to immune checkpoint inhibitors., (© 2022. The Author(s).)

Introduction: Although timely hospital discharge is a complex and multifactorial process, this metric is consistently a focus for hospitals and health care systems. It also has been a long practice that the American Urological Association (AUA) supports the use of advanced practice providers (APPs) as an integral member of the urological care team., Materials and Methods: Here, we performed a preliminary evaluation of the effectiveness of an inpatient APP in reducing hospital length of stay (LOS) following major urologic oncology procedures. Surgical outcomes, surgeon data, and LOS for open and minimally invasive urologic oncology procedures, including radical prostatectomy, partial or radical nephrectomy, and radical cystectomy, were compiled over a 4-year period (pre-APP: 2014-2016 and post-APP: 2018-2020). Univariate descriptive statistics analyzed the association of an inpatient APP in with reducing hospital LOS over time., Results: Average LOS decreased in all surgical procedures and for all surgeons in the post-APP setting, irrespective of surgical approach (P< 0.05)., Conclusions: An inpatient APP was associated with a decrease of hospital LOS for urologic oncology patients over time. Such observations underscore the likely economic benefit to the health care system and potential improved coordination of care and satisfaction for patients undergoing major urologic oncology procedures., Competing Interests: Declaration of Conflicts of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: There is a shortage in the number of urologists needed to satisfy the needs of an aging U.S., Population: The urologist shortage may have a pronounced impact on aging rural communities. Our objective was to describe the demographic trends and scope of practice of rural urologists using data from the American Urological Association Census., Methods: We conducted a retrospective analysis of American Urological Association Census survey data over a 5-year period (2016-2020), including all U.S.-based practicing urologists. Metropolitan (urban) and nonmetropolitan (rural) practice classifications were based on rural-urban commuting area codes for the primary practice location zip code. We conducted descriptive statistics of demographics, practice characteristics and specific rural-focused survey items., Results: In 2020, rural urologists were older (60.9 years, 95% CI 58.5-63.3 vs 54.6 years, 95% CI 54.0-55.1) and were in practice longer (25.4 years, 95% CI 23.2-27.5 vs 21.2 years, 95% CI 20.8-21.5) than urban counterparts. Since 2016, mean age and years in practice increased for rural urologists but remained stable for urban urologists, suggesting an influx of younger urologists to urban areas. Compared with urban urologists, rural urologists had significantly less fellowship training and more frequently worked in solo practice, multispecialty groups and private hospitals., Conclusions: The urological workforce shortage will particularly impact rural communities and their access to urological care. We hope our findings will inform and empower policymakers to develop targeted interventions to expand the rural urologist workforce.

Introduction: In colorectal, cervical, and breast cancers, oncologic follow-up can exacerbate or alleviate patient stress about disease recurrence. Such patient experiences are less well defined for urologic malignancies. We developed a cross-sectional prospective survey study to assess kidney (Kid), prostate (Pros), and bladder (Bld) cancer patient perceptions of oncologic follow-up following surgical treatment., Patients and Methods: Patients with pTanyNanyM0 Kid, Pros, and Bld cancer presenting at least 60 days following primary surgical treatment of their cancer were eligible. Receipt of adjuvant therapy or disease recurrence were exclusion criteria. Questionnaires assessing attitudes towards follow-up and stress-reducing strategies were administered prior to revealing testing results. Analysis was performed according to cancer type and level of recurrence risk, with pathologic stage used a proxy for recurrence risk., Results: Three hundred thirty-seven patients were prospectively surveyed from 2018 to 2020: 127 (38%) Kid, 134 (40%) Pros, and 76 (23%) Bld. Patients showed satisfaction with provided strategies to combat recurrence anxiety (Kid 86%, Pros 81%, Bld 85%). However, approximately 16% of patients reported wanting, but not receiving, strategies for fear reduction. Most patients reported diagnostic tests were "Not at All" burdensome (Kid 86%, Pros 94%, Bld 82%) and disagree that fewer tests would alleviate anxiety (Kid 89%, Pros 91%, Bld 84%). The majority reported an increased sense of worry if there were no cancer follow-ups (Kid 84%, Pros 80%, Kid 81%), and preferred their specialist to their family physician to direct such care (Kid 89%, Pros 91%, Bld 95%). When stratified by recurrence risk, no significant differences existed across cancers in patients' attitudes toward follow-up. However, Pros cancer patients showed a difference in fear of recurrence ("Not at All" worried about recurrence ≤T2 38%, ≥T3, 19%; P= .04)., Conclusion: Urology patients appear satisfied with their oncologic follow-up. Sixteen percent of patients sought additional strategies to combat fear, indicating opportunity for improvement., Competing Interests: Disclosure None., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Despite guidelines recommending that staging imaging is not needed in very low-risk (VLR) and low-risk (LR) prostate cancer (PCa), there is concern for overutilization in these risk groups. We investigate utilization of staging imaging and implications of findings in newly diagnosed VLR and LR PCa patients., Methods: A total of 493 patients diagnosed with PCa between 2011 and 2017 were stratified according to American Urological Association and National Comprehensive Cancer Network® VLR and LR groups. Computerized tomography (CT), magnetic resonance imaging and bone scan performed at diagnosis was captured and guidelines compliance was evaluated. The significance of radiologist interpreted imaging findings, by imaging type, were classified as normal, nonurological, nonsignificant urological and PCa significant., Results: Greater than 75% of patients in the VLR and LR groups underwent imaging at time of diagnosis. Bone scan was performed in 30% of patients, none of which noted PCa-significant findings, and the majority were normal. CT was utilized in 38% of patients, with only 3 showing PCa-significant findings. Ten CTs showed nonurological/nonsignificant urological findings causing further evaluation. Magnetic resonance imaging was the most utilized scan in low-risk groups, occurring in 70% of patients. Although the majority were normal, 25 scans showed nonsignificant urological findings while only 7 showed PCa-significant findings., Conclusions: Among VLR and LR PCa patients, there is high overutilization of imaging with most studies yielding minimal PCa-significant findings and further evaluation for incidental observations. This exploratory analysis gives awareness that staging imaging in VLR and LR PCa patients may do more harm than good.

Background: The 2017 AUA White Paper on prevention of prostate needle biopsy (PNB) complications highlights an algorithm for reducing procedural related infections. The incorporation of topical rectal antiseptic (TRS) at time of transrectal PNB is listed as one such modality. We present data on over 1000 transrectal PNB procedures to determine the impact of TRS on 1) infectious complications and 2) use of augmented procedural antibiotics., Methods: The records of 1181 transrectal PNB procedures performed over a 10-year period were reviewed. In 2013, TRS with either 10% povidone iodine or 4% chlorhexidine was more regularly incorporated into PNB procedures. Clinical and procedural factors were analyzed for association with post-procedure infections. Infectious complications outcomes were compared in patients receiving TRS (n = 566) versus those who had not (n = 615)., Results: A total of 990 men underwent 1181 transrectal PNB procedures. Median age of the cohort was 63 years with a median PSA of 7 ng/dL. Of them, 86% of the men were Caucasian, 28% had undergone at least one prior biopsy, 14% were diabetic, and 6% had prior hospitalization within 6 months of the procedure. Five hundred sixty-six patients (48%) received TRS at time of biopsy. Perioperative IV adjunctive antibiotics were used less frequently in patients receiving TRS (13.4% vs. 28.6%, p < 0.001). Furthermore, patients receiving TRS experienced lower rates of clinical infections (1.2% vs. 2.4%, p = 0.14), as well as lower likelihood of severe infections evidenced by decreased rates of hospital admission (0.5% vs. 2.3%, p = 0.013). Rectal vault bacteriology obtained before and after TRS was available in 180 men noting a 98.1% decrease in colony counts after local treatment., Conclusions: TRS at time of transrectal PNB was associated with decreased use of IV procedural antibiotics as well as decreased severity of infections post-biopsy. This simple technique enhances antibiotic stewardship while simultaneously improving quality outcomes of the procedure., Competing Interests: None., (© 2021 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

Purpose of Review: To review the integration of robotics in urology residency programs and evaluate how it has impacted a graduates' level of surgical competence., Recent Findings: Surgical technique training has shown a dramatic shift towards robotics with the most profound occurring in oncology. However, integration of robotics is not uniform across programs nor even among residents themselves. Robotics require graduates to garner a broader skill set within the same prescribed training time. Unfortunately, in this modern era, graduates are feeling more ill-equipped to start independent practice and show an increased need to pursue fellowship training to achieve technical proficiency. The dissemination of robotics in residency programs has gone unchecked. Modulating existing training structures through (1) development of procedure- and surgical technique-specific target metrics for graduation and (2) integration of a formalized robotic curriculum may improve the overall quality and outcome of the educational experience., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The American Urological Association's (AUA) and National Comprehensive Cancer Network's (NCCN) provide highly recognized guidelines for staging prostate cancer (CaP). However, both are vague as to specific type of cross-sectional imaging (CT vs. MRI) and extent (abdominal vs. pelvis), thereby raising concern for overlapping imaging. We investigated if current AUA and NCCN CaP staging guidelines can become more specific yet maintain sufficient staging., Methods: We identified 493 patients diagnosed with CaP between 2011 and 2017 and focused analysis on those with AUA and NCCN Intermediate risk (IR) and High risk (HR) groups. Type of staging imaging was recorded and frequency of overlapping (CT + MRI) and abdominal imaging determined. Significance of radiologist findings, for both overlapping and abdominal imaging, were classified as nonurologic, nonsignificant urologic, and CaP significant., Results: Among IR and HR AUA and NCCN risk groups, 82 (35.7%) and 95 (37.3%) patients, respectively, experienced overlapping imaging, of which only 7 patients in AUA and 9 patients in NCCN risk groups had an abnormal CT with normal MRI. However, only 3 of these CTs had CaP significant findings, of which 2 identified bone metastases, which were subsequently detected on bone scan. In regard to the extent of imaging, a total of 157 (68.2%) AUA and 178 (69.8%) NCCN IR and HR patients received abdominal scans, of which only 46 (20.0%) and 49 (19.2%) were abnormal among AUA and NCCN risk groups, respectively. Among these abnormal abdominal scans, only 10 showed CaP significant findings, of which half were suspected bone metastases, and confirmed on recommended bone scan., Conclusions: Due to nonspecific staging guidelines in IR and HR CaP regarding type and extent of cross-sectional imaging, patients are frequently receiving imaging of overlapping locations. Based on low occurrences of unique CaP significant findings on CT and abdominal imaging, our exploratory analysis suggests that narrowing cross-sectional imaging recommendations to pelvic MRI may reduce imaging overlap while maintaining sufficient staging., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Imaging characteristics in bladder cancer (BC), such as hydronephrosis, are predictive of ≥ pT3 disease at time of radical cystectomy (RC). The predictive capacity of other findings, such as perivesical stranding (PS), remains unclear. We investigated whether PS was associated with ≥ pT3 BC in patients who did not receive neoadjuvant chemotherapy (NAC)., Methods: We identified 433 patients with BC who underwent RC from 2003 to 2018 of which 128 did not receive NAC. Evidence of PS on pre-TURBT imaging was determined by radiologist review and a stranding grading system was created. Factors associated with PS and hydronephrosis were identified. Multivariable logistic regressions evaluated PS and hydronephrosis as predictors for ≥ pT3 BC., Results: Of the 128 patients who did not receive NAC, 48 (38%) had pT3 and 12 (9%) had pT4 BC. 125 (98%) patients had CT and three (2%) had MRI. PS and hydronephrosis on imaging were identified in 19 (15%) and 45 (35%) patients. PS was not associated with imaging type (p = 0.38), BMI (p = 0.18), or pathologic T stage (p = 0.24). Hydronephrosis was more frequently associated with higher pathologic T stage (p = 0.034). Multivariable analysis demonstrated that PS was not predictive of ≥ pT3 BC (p = 0.457), while hydronephrosis was positively associated (p = 0.003). Stratification by grade of stranding did not improve the predictive capacity of PS (p = 0.667)., Conclusion: While hydronephrosis is an indicator of higher stage BC, PS failed to be a reliable predictor of ≥ pT3 stage. These observations should give pause in using PS on imaging to guide decisions until further investigations can be explored.

Purpose: Surveillance guidelines for kidney cancer following surgery are heterogeneous, making it unclear what factors influence surveillance intensity in practice. Thus, we assessed the patterns of surveillance intensity in kidney cancer after primary surgery among patients ≥ 66 years., Methods: Non-metastatic kidney cancer patients after primary surgery (n = 2433) from 2007 to 2011 were identified in SEER-Medicare. Surveillance intensity was measured as the number of unique inpatient and outpatient claims made for kidney cancer starting 60 days after primary surgery. Multivariable linear regressions assessed relationships between patient factors and surveillance intensity (log-transformed). Parameters were reported using risk ratios (RRs)., Results: Patients diagnosed in contemporary years experienced 10% more surveillance visits/12 months (RR 1.10 for every 1-year increase, 95% CI 1.07-1.13, p < 0.001). Compared to pT1 stage, patients with pT2-4 disease experienced 108% more surveillance visits/12 months (RR 2.08, 95% CI 1.90-2.27, p < 0.001). Both older age and living in a metro/urban area, as compared to a big metropolitan location, were associated with significantly fewer follow-up visits (10-year increase in age: RR 0.89, 95% CI 0.83-0.95, p < 0.001; metro/urban: RR 0.86, 95% CI 0.79-0.93, p < 0.001). Surgery type (radical, partial or ablation), gender, race and Charlson comorbidity score were not significantly associated with surveillance intensity., Conclusions: Similar to guidelines, surveillance intensity in practice was associated with stage, but not with surgery type. Other factors such as diagnosis year, care location and patient age were associated with the amount of surveillance administered by the clinician. These additional influences are augmenting the heterogeneous delivery of kidney cancer surveillance care.

Objective: To evaluate postoperative recurrence patterns for high-risk nonmetastatic renal cell carcinoma (RCC) and to identify prognostic factors associated with site-specific metastatic recurrence using a multi-institutional contemporary cohort., Methods: Data for nonmetastatic ≥pT3a RCC patients treated with surgery at 4 independent centers was analyzed. Initial recurrence locations were identified, and imaging templates were defined by anatomic landmarks using radiologic definitions. Prognostic factors for site specific recurrence were evaluated with univariate and multivariable analyses., Results: A total of 1057 patients were treated surgically for ≥pT3a RCC. Initial recurrence location was in a single site for 160 (59.3%) patients and at multiple locations in 110 (41.7%) patients. The most common sites of metastatic recurrence were lung (144/270, 53.3%), liver (54/270, 20.0%), and bone (48/270, 17.8%). Recurrence was identified in 52 of 270 (19.3%) patients outside the chest/abdomen template, most commonly in the pelvis (25/270, 9.3%). Bone and brain metastases were the most common organs for metastases outside chest/abdomen. Patients with tumor diameter >10 cm and grade 4 were more likely to recur in the bone (HR 3.61, P <.001) and brain (HR 16.5, P <.001)., Conclusion: Metastatic progression outside chest/abdomen imaging templates was present in 1 of 5 high risk patients at initial metastatic RCC diagnosis, most commonly in the pelvis. Patients with large (>10 cm) tumors and grade 4 histology are at highest risk for bone and brain metastases., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To evaluate the ability of hemostatic agents (HA) to limit bleeding complications following partial nephrectomy (PN) and determine HA usage and costs as well as factors associated with post-operative bleeding complications., Methods: The records of 429 PN performed for kidney cancers were reviewed for clinical, pathologic, and perioperative variables. Surgical approach, HA use, and HA expenditure were determined. Bleeding complications and management to 90 days after PN were annotated. Wilcoxon rank-sum and two-sample t tests identified factors associated with HA use. Univariate and limited multivariate logistic regression determined variables associated with bleeding complications., Results: Use of HA was associated with longer OR duration, longer ischemia time, higher EBL, and method of PN (OPN and LPN > RPN) (all p values < 0.001). On bivariate analysis, while multiple factors were associated with bleeding complications, neither HA use (p = 0.924) nor the number of HA used (two agents vs one p = 0.712; three agents vs. one p = 0.606) were. A multivariable model noted that increasing RENAL score (p = 0.013) and surgical approach (OPN vs. RPN [p = 0.009] and LPN vs. RPN (p = 0.002]) were independently associated with bleeding complications, while HA use was not (p = 0.294). During the 16 years of analysis, a total of $77,687 USD was spent on HA. Average annual HA expenditure was $4855 USD with the peak being in 2010 where expense was $14,086. Mean annual costs for HA use were greater for OPN vs RAPN starting in 2013 (p = 0.02) CONCLUSIONS: The use of HA during PN was not associated with lower rates of bleeding complications. Therefore, judicious use in a case-specific manner is requisite to limit potentially unnecessary operative cost.

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovascular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0-7 cm) tumors, pT1b (4-7 cm) RCC masses were more likely to have necrosis (43% vs 16%, P < 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P < 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0-4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all < 0.001) when compared to pT1 masses. For masses <4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P < 0.001), LVI (22% vs 2%, P < 0.001), high-grade nuclear elements (45% vs 17%, P < 0.001), and sarcomatoid features (12% vs 0%, P < 0.001) compared to pT1a tumors. Similarly, for masses 4-7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (12% vs 2%, P = 0.006) and LVI (22% vs 6%, P = 0.003) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses >4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass., Competing Interests: The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article., (Copyright: Nahouraii LM et al.)

Purpose: A minimum number of index procedures is required for graduation. Without thresholds for surgical technique, it is unclear if robotic and open learning is balanced. We assessed the distribution of robotic and open surgeries performed by residents upon graduation., Materials and Methods: Voluntary Accreditation Council for Graduate Medical Education resident case logs from 11 institutions were de-identified and trends in robotic and open major surgeries were compared using Wilcoxon rank sum and 2-sample t-tests., Results: A total of 89,199 major cases were recorded by 209 graduates from 2011 to 2017. The median proportion of robotic cases increased from 2011 to 2017 in reconstruction (4.7% to 15.2%), oncology (27.5% to 54.2%) and pediatrics (0% to 10.9%) (all values p <0.001). Robotic and open cases remained most divergent in reconstruction, with a median of 12 robotic (IQR 9-19) to 70 open cases (IQR 55-106) being performed by residents in 2017. Similar observations occurred in pediatrics. In oncology the number of robotic procedures superseded that of open in 2016 and rose to a median of 148 robotic (IQR 108-214) to 121 open cases (IQR 90-169) in 2017, with the driver being robotic prostatectomy. Substantial differences in surgical technique were observed between institutions and among graduates from the same institution., Conclusions: Although robotic volume is increasing, the balance of surgical technique and the pace of change differ in reconstruction, oncology and pediatrics, as well as among individual institutions and graduates themselves. This raises questions about whether more specific guidelines are needed to ensure equity and standardization in training.

Introduction: The purpose of this study was to explore whether the practice of postoperative renal cell carcinoma (RCC) surveillance affords a survival benefit by investigating whether detection of RCC recurrences in an asymptomatic versus symptomatic manner influences mortality., Patients and Methods: We identified 737 patients who underwent partial or radical nephrectomy for M0 RCC between 1998 and 2016. Overall survival and disease-specific survival stratified by the type of recurrence detection (asymptomatic vs. symptomatic) was estimated using Kaplan-Meier probabilities both from the time of surgery and from the time of recurrence. Cox proportional hazard regression models were used to evaluate the impact of the type of recurrence detection on mortality., Results: A total of 78 patients (10.6%) experienced recurrence after surgery, of whom 63 (80.8%) were asymptomatic (detected using routine surveillance) and 15 (19.2%) were symptomatic. The median postoperative follow-up was 47.2 months (interquartile range, 26.3-89.4 months). Five- and 10-year overall survival, from time of surgery, among patients with asymptomatic versus symptomatic recurrences was 57% and 39% versus 24% and 8%, respectively (P = .0002). As compared with asymptomatic recurrences, patients with symptomatic recurrences had an increased risk of overall (OD) and disease-specific death (DSD) both when examined from the time of surgery (OD: hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.33-7.49; P = .0091 and DSD: HR, 3.44; 95% CI, 1.38-8.57; P = .0079) and from the time of recurrence (OD: HR, 2.93; 95% CI, 1.24-6.93; P = .0143 and DSD: HR, 3.62; 95% CI, 1.45-9.01; P = .0058)., Conclusions: Capturing RCC recurrences in an asymptomatic manner during routine surveillance is associated with improved patient survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Measures of mitotic activity predict behavior of noninvasive papillary urothelial carcinoma of the urinary bladder, but it is unclear what role these should have in tumor grading. In this article, we compare measures of mitotic activity to contemporary tumor grading, specifically in their association with recurrence of noninvasive papillary urothelial carcinoma. The study uses a retrospective cohort of 199 tumors from 124 patients. Mitotic activity was treated as a categorical variable (mitotic-inert, mitotic-low, or mitotic-high). Evaluating only first-occurrence tumors, recurrence was more frequent in mitotic-high (hazard ratio [HR], 8.8; P < .0001, Cox model) and mitotic-low tumors (HR, 3.7; P = .017) compared with mitotic-inert tumors, when controlling for treatment with intravesical bacillus Calmette-Guerin, age, and sex. Recurrence was likewise more frequent in high-grade tumors (HR, 3.1; P = .00019, Cox model) compared with low-grade tumors, controlling for these factors. However, mitotic group, but not tumor grade, was significantly associated with recurrence in a multivariate Cox model including mitotic group, tumor grade, and treatment status (HR, 6.5 [P = .0025] for mitotic-high versus reference; HR, 3.7 [P = .018] for mitotic-low versus reference). Frailty models including both first-occurrence and recurrent tumors showed similar results. Isolating the analysis to first occurrence, low-grade tumors, recurrence was more frequent in mitotic-high (HR, 6.8; P = .0044, Cox model) and mitotic-low (HR, 3.4; P = .027) tumors compared with mitotic-inert tumors. The findings indicate that mitotic activity is associated with behavior of noninvasive papillary urothelial carcinoma and may be valuable as an adjunct to the contemporary grading system., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To provide an alternative surveillance approach for bladder cancer (BC) following radical cystectomy (RC) according to more accurate predictions of a patient's projected BC course., Methods: We identified 1797 patients who underwent RC for M0 BC between 1980 and 2007. Patients were stratified by pathologic stage (pT0Nx-0, pTa/CIS/1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN+), relapse location (urethra, upper tract, abdomen/pelvis, chest, and other), age (≤60, 61-70, 71-80, >80 years) and Charlson Co-morbidity Index (CCI ≤2 and CCI ≥3). Risks of disease recurrence and non-BC death were modeled using Weibull distributions. Recommended surveillance durations were estimated when the risk of non-BC death exceeded the risk of recurrence., Results: At a median follow-up of 10.6 years (IQR 6.8,15.2), 713 patients developed recurrence. Vastly different recurrence patterns were appreciated. Specifically, among patients ≤60 years with pT2Nx-0, non-BC death risk exceeded the risk of recurrence in the abdomen at 7.5 years following surgery when CCI was ≥3, versus at year 10 after RC when CCI was ≤2. Meanwhile, for patients >80 years with pT2Nx-0, non-BC death risk exceeded the risk of abdominal recurrence at 1 year after RC, regardless of CCI., Conclusion: We present an alternative post-RC surveillance approach that incorporates a patient's changing risk profile with the influence of competing health factors. We believe this strategy provides more individualized recommendations than current guidelines, and may improve the benefit derived from surveillance while reducing resource misappropriation.

Postoperative surveillance is an integral part of renal cell carcinoma (RCC) care. However, evidence supporting the practice is lacking. RCC guidelines offer disparate recommendations leading to variation in care. Recently, the effectiveness of guidelines has been questioned and a debate has ignited over whether current protocols merit optimization. Guidelines show limitations in RCC risk assessment, protocol stratification, and definition of duration of follow-up. Alternative strategies have addressed some of these limitations, but further analysis is warranted. Until challenges with assessing a survival benefit are negotiated, efforts should be made to optimize and standardize guidelines and learn of more tangible benefits to surveillance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the safety and utility of more aggressive surgical resection of renal cell carcinoma involving the liver at the time of nephrectomy., Materials and Methods: We identified 34 cases at our institution where patients underwent simultaneous nephrectomy and hepatic resection for direct hepatic invasion (n = 17) or metastatic renal cell carcinoma (n = 21). Perioperative outcomes and complication rates were compared with a matched referent cohort (n = 68) undergoing simultaneous nephrectomy and resection of non-hepatic locally invasive or metastatic disease., Results: Of the 34 cases, 17 (50%) patients underwent hepatic resection for pT4 liver involvement and 21 (62%) patients underwent simultaneous nephrectomy and hepatic metastasectomy. Deep vein thrombosis occurred more frequently following hepatic resection (15% vs 1%, P = .02); however, no significant differences were noted in Clavien grade 3-4 complications (12% vs 3%, P = .10) or perioperative mortality (3% vs 0%, P = .67). Two-year cancer-specific and overall survival for patients undergoing hepatic resection and non-hepatic resection were 40% and 29% (hazard ratio: 0.72, P = .2) and 40% and 28% (hazard ratio: 0.80, P = .30), respectively., Conclusion: In carefully selected patients, hepatic resection at the time of nephrectomy is associated with a higher risk of deep vein thrombosis and may be associated with a trend toward an increased risk of short-term Clavien IV complications; however, perioperative and overall mortality are comparable with those in matched patients undergoing surgical resection of locally advanced or metastatic disease involving non-hepatic organs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To describe the clinicopathological features associated with increased risk of renal fossa recurrence (RFR) after radical nephrectomy (RN) and to describe the prognostic features associated with cancer-specific survival (CSS) among patients with RFR treated with primary locally directed therapy, systemically directed therapy or expectant management., Patients and Methods: The records of 2 502 patients treated with RN for unilateral, sporadic, localized renal cell carcinoma (RCC) between 1970 and 2006 were reviewed. CSS after RFR was estimated using the Kaplan-Meier method. Associations with the development of RFR and CSS after RFR were evaluated using Cox proportional hazards regression models., Results: A total of 33 (1.3%) patients developed isolated RFR (iRFR) and 30 (1.2%) patients developed RFR in the setting of synchronous metastases after RN (study cohort, N = 63). The median follow-up for the series was 9.0 years after RN and 6.0 years after RFR diagnosis. On multivariable analysis, advanced pathological stage (pT2: hazard ratio [HR] 4.36, P = 0.004; pT3/4: HR 4.39, P = 0.003) and coagulative necrosis (HR 2.71, P = 0.006) were independently associated with increased risk of iRFR. The median time to recurrence was 1.5 years after RN among the 33 patients with iRFR, and 1.4 years among all patients. Overall, the median CSS was 2.5 years after diagnosis of iRFR, 1.3 years after RFR in the setting of synchronous metastases, and 2.2 years overall. After primary locally directed therapy (surgery, ablation or radiation), systemic therapy or expectant management, the 3-year CSS rates among patients with iRFR were 63%, 50% and 13% (P = 0.001) and were 64%, 50% and 28% (P = 0.006) among all patients, respectively. On multivariable analysis, when compared with observation, locally directed therapies were associated with a significantly decreased risk of death from RCC (HR 0.26, P < 0.001)., Conclusions: Renal fossa recurrence is a rare event after RN for RCC and portends a poor prognosis, even in the absence of synchronous metastases. Development of iRFR is associated with advanced stage and aggressive tumour biology. Patients who underwent primary locally directed therapy had superior CSS compared with those treated with expectant management, supporting the use of aggressive local treatment in carefully selected patients with RFR. Future research is needed to determine the optimum role and sequencing of combined therapy in patients with this rare entity., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate the concordance of pathologic features in metastatic renal cell carcinoma (RCC) between the primary nephrectomy and metastasectomy specimens., Methods: Primary nephrectomy (n = 454) and matched metastasectomy specimens (n = 680) from patients treated between 1970 and 2009 for RCC were re-reviewed by 1 urologic pathologist in a blinded fashion. RCC histologic subtype, grade, coagulative necrosis, and the presence of sarcomatoid differentiation were compared between the primary and the metastatic tumor with kappa statistics., Results: Concordance with the primary tumor was observed for subtype in 647 (95%, kappa = 0.71) of the metastases, for grade in 411 (60%, kappa = 0.35), necrosis in 460 (68%, kappa = 0.32), and sarcomatoid differentiation in 643 (95%, kappa = 0.60). Upgrading was observed in 100%, 63%, and 13% of patients with grades 1, 2, and 3 primary tumors, respectively (no patient had a grade 1 metastatic lesion). Metastatic tumors treated with metastasectomy within 30 days of nephrectomy (n = 145) had similar rates of concordant subtype, necrosis, and sarcomatoid differentiation to those undergoing metastasectomy beyond 30 days from nephrectomy (P >.05 for all), but had higher rates of concordant grade (71% vs 58%, P = .003). Pre-metastasectomy exposure to systemic targeted or immunotherapy was not associated with a change in concordance of histopathologic features., Conclusion: Among 454 surgically managed metastatic RCC patients, we observed a high degree of concordance for histologic subtype and sarcomatoid differentiation, and varying degrees of discordance for grade and coagulative tumor necrosis, between primary and metastatic tumors. Further investigation is warranted to understand the biologic and therapeutic implications of these observations., (Published by Elsevier Inc.)

Purpose: Multiple definitions of biochemical recurrence for prostate cancer exist after radical prostatectomy, and variation continues in prostate cancer outcome reporting and secondary treatment initiation. We reviewed long-term prostatectomy outcomes to assess the most appropriate prostate specific antigen cut point that predicts future disease progression., Materials and Methods: We identified 13,512 patients with cT1-2N0M0 prostate cancer who underwent radical prostatectomy between 1987 and 2010. Single prostate specific antigen cut points of 0.2, 0.3, 0.4 and 0.5 ng/ml or greater, as well as confirmatory prostate specific antigen value definitions of 0.2 ng/ml or greater followed by prostate specific antigen greater than 0.2 ng/ml and 0.4 ng/ml or greater followed by prostate specific antigen greater than 0.4 ng/ml were tested. Continued prostate specific antigen increase after a designated cut point definition was estimated using cumulative incidence. The strength of association between biochemical recurrence definitions and subsequent systemic progression were analyzed using Cox proportional hazard models and the O'Quigley event based R(2) test., Results: At a median postoperative followup of 9.1 years (IQR 4.9-14.3) a detectable prostate specific antigen developed in 5,041 patients and systemic progression developed in 512. After reaching the prostate specific antigen cut point of 0.2, 0.3 and 0.4 ng/ml, the percentage of patients experiencing a continued prostate specific antigen increase over 5 years was 61%, 67% and 74%, respectively, plateauing at 0.4 ng/ml. The strongest association between biochemical recurrence and systemic progression occurred using a single prostate specific antigen cut point of 0.4 ng/ml or greater (HR 36, R(2) 0.92)., Conclusions: A prostate specific antigen cut point of 0.4 ng/ml or greater reflects the threshold at which a prostate specific antigen increase becomes durable and shows the strongest correlation with subsequent systemic progression. Consideration should be given to using a prostate specific antigen of 0.4 ng/ml or greater as the standard biochemical recurrence definition after radical prostatectomy., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The existing guidance on bladder cancer surveillance following radical cystectomy is limited and variable. Additionally, the effect of surveillance on mortality is debatable. Herein, we perform a systematic review to evaluate the characteristics of alternative oncologic surveillance protocols and determine the association of detection of asymptomatic vs. symptomatic recurrences on mortality., Methods: An electronic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases was performed from 1970 to 2015. In all, 3 reviewers independently assessed the 1,729 candidate studies for eligibility and abstracted data based on an a priori established protocol. Outcomes were pooled using random effects meta-analysis., Results: We identified 7 studies for inclusion that were uncontrolled and thereby represented a body of evidence at high risk of bias; 5 studies developed surveillance protocols using a methodology similar to that of established guidelines. The majority proposed a pathologic stage-stratified approach, but ended surveillance for all patients at 5 years. Detection of asymptomatic recurrences was associated with a nonsignificant reduction in mortality (relative risk = 0.78; 95% CI: 0.58-1.04). This effect became statistically significant when upper and lower urinary tract recurrences were included in the analyses (relative risk = 0.69; 95% CI: 0.59-0.79)., Conclusions: Only sparse evidence supports alternative oncologic surveillance protocols for bladder cancer following radical cystectomy. The majority of existing protocols proposed similar strategies to those recommended by published guidelines. Detecting asymptomatic recurrences may lead to a reduction in overall mortality, which could provide a rationale for surveillance., (Copyright © 2016. Published by Elsevier Inc.)

Purpose: We evaluate the association between severe skeletal muscle deficiency or sarcopenia, and disease progression, cancer specific mortality and all cause mortality in patients with localized renal cell carcinoma treated with radical nephrectomy., Materials and Methods: The baseline lumbar skeletal muscle index of 387 patients treated with radical nephrectomy for nonmetastatic renal cell carcinoma between 2000 and 2010 was measured on preoperative computerized tomography. Sarcopenia was classified according to gender specific consensus definitions as male-skeletal muscle index less than 55 cm(2)/m(2) and female-skeletal muscle index less than 39 cm(2)/m(2). Progression-free, cancer specific and overall survival was estimated with the Kaplan-Meier method. Associations with progression, cancer specific mortality and all cause mortality were summarized with hazard ratios., Results: Of 387 patients 180 (47%) had sarcopenia. Patients with sarcopenia were older, more likely to be male (77% vs 56%, p <0.001), to have a smoking history (67% vs 55%, p=0.02), and to have nuclear grade 3 or greater disease (67% vs 60%, p=0.05), but were otherwise similar to patients without sarcopenia. Median postoperative followup was 7.2 years. Patients with sarcopenia had inferior 5-year cancer specific survival (79% vs 85%, p=0.05) compared to those without sarcopenia, as well as significantly worse 5-year overall survival (65% vs 74%, p= 0.005). As a continuous variable, increasing skeletal muscle index was linearly associated with a decreased risk of cancer specific mortality and all cause mortality. Moreover, on multivariable analysis sarcopenia was associated with increased cancer specific mortality (HR 1.70, p=0.047) and all cause mortality (HR 1.48, p=0.039)., Conclusions: Sarcopenia is independently associated with cancer specific mortality and all cause mortality after radical nephrectomy for renal cell carcinoma. These findings underscore the importance of assessing skeletal muscle index for risk stratification, patient counseling and treatment planning., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death., Patients and Methods: We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (< 50, 50 to 59, 60 to 69, 70-79 and ≥ 80 years), and Charlson comorbidity index (CCI; ≤ 1 and ≥ 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence., Results: At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx-0 disease and a CCI ≤ 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI ≥ 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age., Conclusion: We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation., (© 2015 by American Society of Clinical Oncology.)

Background: Evidence supporting surveillance guidelines after radical cystectomy (RC) are lacking. Herein, we evaluate the ability of the National Comprehensive Cancer Network (NCCN) guidelines and the European Association of Urology (EAU) guidelines to capture recurrences and provide an alternative approach that balances risks of recurrence with non-bladder cancer death., Methods: We identified 1,797 patients who had M0 urothelial carcinoma who underwent RC at our institution between 1980 and 2007. The success of current guidelines to capture recurrences was assessed by calculating the percentage of recurrences detected during the recommended follow-up time: the NCCN--2 years and the EAU--5 years. An alternative protocol was created using Weibull distributions, which estimate when a patient׳s risk of non-bladder cancer death exceeds their risk of recurrence., Results: At a median follow-up of 10.6 years (interquartile range : 6.8-15.2), a total of 714 patients recurred. Of these, 491 (68.7%) would have been detected by the NCCN guidelines and 642 (89.8%) by the EAU guidelines. Using a risk-adapted approach, vastly different surveillance durations were appreciated. For example, for patients older than 80 years with pT0Nx-0 or pTa/CIS/1Nx-0 disease, recurrence risk to any location never exceeded their risk of non-bladder cancer death, whereas for patients aged 60 years and younger with pT3/4Nx-0 or pTanyN+disease, risk of abdominal/pelvis recurrence remained greater than their risk of non-bladder cancer death for>20 years., Conclusions: The duration of post-RC follow-up recommended by the NCCN and the EAU does not comprehensively capture recurrences. A surveillance algorithm based on the interaction between recurrence risk and competing health factors individualizes recommendations and may improve capture of recurrences and resource allocation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of Peru's national folic acid fortification program on folic acid content in wheat flour, and the effect on birth prevalence of neural tube defects (NTDs) in Lima, and to compare the program's legislative requirements with international standards., Methods: Bread was sampled from six sites across Peru and tested for folic acid. Data were obtained from the largest obstetric hospital in Lima on the prevalence of births (live and still) with NTDs during both the pre-fortification period (2004-2005) and post-fortification years (2007-2008)., Results: Folic acid content in the sampled bread met national legislative requirements but was less than one-half of the level recommended for Peru by the World Health Organization (WHO) (2.6 mg/kg wheat flour). Birth prevalence of NTDs was 18.4/10 000 in the pre-fortification period and 20.0/10 000 during post-fortification years. Relative risk for NTDs after fortification was 1.02 (95% confidence interval 0.77-1.35, P = 0.90)., Conclusions: Peruvian legislative requirements for folic acid fortification are below international (WHO) recommendations; birth prevalence of NTDs in Lima is higher than international benchmarks; and no decrease in NTDs following fortification of flour with folic acid (according to Peruvian national standards) was observed. As increasing the level of folic acid in flour remains the most sustainable way of preventing NTDs, it is recommended that Peru increase its folic acid fortification requirements to meet those recommended by WHO (2.6 mg/kg).

Acid fuchsin and phloxine B are commonly used to stain plant-parasitic nematodes in roots and egg masses on root surfaces, respectively. Both stains can be harmful to both the user and the environment and require costly waste disposal procedures. We developed safer methods to replace both stains using McCormick Schilling red food color. Eggs, juveniles, and adults of Meloidogyne incognita stained in roots with red food color were equally as visible as those stained with acid fuchsin. Egg masses stained with red food color appeared as bright-red spheres on the root surfaces and were highly visible even without magnification. Replacement of acid fuchsin and phloxine B with red food color for staining nematodes is safer for the user and the environment, and eliminates costly waste disposal of used stain solutions.

This case study describes the Camden City Health Improvement Learning Collaborative (the Collaborative), a community care network initiative formed in 1993. The organization is composed of representatives from local healthcare providers, public agencies, religious organizations, and neighborhoods. The major goal of this initiative is to improve the health status of the community by involving and empowering residents in the solution of their needs. The Collaborative represents a grassroots strategic model of community inclusion in the formulation of goals and programs to improve community health status. The case study describes the dynamics of the Collaborative by examining the following: historical development; political, institutional, and social context; planning process; organization and structure; and performance evaluation. The article concludes with a discussion of the strategic and operational lessons learned from the Collaborative.

Thirty-six servicemen were anaesthetised using the Triservice anaesthetic apparatus. They were allocated randomly into one of two groups, to breathe spontaneously or to receive artificial ventilation, and into subgroups who were given air alone, or air supplemented with 1 or 4 litres/minute of oxygen. A further 12 subjects were studied subsequently using 0.5 litres/minute of added oxygen. Intra-operative blood gases were compared with those of awake premedicated controls. Artificial ventilation was associated with an unchanged arterial oxygen tension with air alone; in the other subgroups arterial oxygen tension was higher than with spontaneous respiration when related to inspired oxygen fraction (p less than 0.05). Air anaesthesia caused significant hypoxaemia with spontaneous ventilation (p less than 0.05), and 50% of the subjects required assisted ventilation. There was also a significant respiratory acidosis (p less than 0.05). Intermittent positive pressure ventilation is the method of choice for field anaesthesia when oxygen is unavailable. Spontaneous respiration must be supplemented with at least 0.5 litres minute of oxygen.

A case of fat embolism with known Eisenmenger syndrome is described, in whom the right-to-left shunt appeared to protect the patient from further hypoxaemia. The potential value of an intravenous filter to eliminate air in patients with reversed intracardiac shunts is noted.

The work of nine Naval anaesthetists deployed with the Task Force during the Falklands campaign is described. The anaesthetists worked in a field hospital (Ajax Bay), a hospital ship (SS Uganda), a troop ship (SS Camberra), aircraft carriers (HMS Hermes and HMS Invincible) and a Royal Fleet Auxiliary (Tidespring). The problems of staffing and providing the stores for various teams in different locations at short notice are discussed.