Open or robotic? Radical cystectomies for patients with non-metastatic bladder cancer: A systematic review and meta-analysis.

Background: This systematic review and meta-analysis will review randomized control trials for localized bladder cancer, evaluating surgical and pathologic outcomes of ORC versus RARC. Methods: Randomized studies evaluating adults with non-metastatic bladder cancer who underwent a radical cystectomy. Randomized trials were selected for final review. Data was extracted and analyzed with Revman 5 software. The primary outcome was complication rates within 90 days. Secondary outcomes included postoperative quality of life, estimated intraoperative blood loss, and other perioperative outcomes. Continuous variables were reported using mean difference with 95% confidence intervals, and dichotomous variables were reported using risk difference with 95% confidence intervals with RARC as the experimental group and ORC as the reference group. Results: Of 134 articles screened, six unique randomized studies were selected. For Grade I-II complications, the risk ratio (RR) was 0.92 (95% CI [0.79,1.08], p = 0.33), and for Grade III-V complications, RR 0.93 (95% CI [0.73,1.18], p = 0.59). RARC resulted in decreased blood loss (95% CI [-438.08, -158.44], p < 0.00001) and longer operative time (95% CI [55.23, 133.13], p < 0.00001). Quality of life using the EORTC-QLQ-30 global health score at 3 months post-op appeared to favor RARC with a mean difference of 4.46 points (95% CI [1.78, 7.15], p = 0.001). Pathologic outcomes neither statistically nor clinically favored one modality, as there was no significant difference between mean lymph node yield (p = 0.49), positive lymph nodes (p = 1.00), and positive surgical margins (p = 0.85) between the surgical modalities. Conclusions: Although one surgical modality is not overtly superior, the choice may be decided by mitigating individual operative risk factors like intraoperative blood loss, operative time, post-operative quality of life, as well as institutional costs and learning curve among surgeons.

The Development of a Video-based Nutrition Education Curriculum for Patients Undergoing Radical Cystectomy.

BACKGROUND: The treatment for patients with muscle-invasive bladder cancer includes neoadjuvant chemotherapy followed by radical cystectomy. The American Urological Association guidelines stress the optimization of patient performance status in the perioperative setting. Therefore, implementation of nutrition education is critical for the multi-disciplinary care of this vulnerable patient population and wide distribution of information is critical. OBJECTIVE: The goal of our study was to create a nutrition-based video education series for patients undergoing chemotherapy and radical cystectomy for bladder cancer. METHODS: Scripts for the videos were developed through an iterative process by experts in nutrition, urology, and communication. Providers and patient advocates were recruited to perform semi-structured interviews and surveys for additional feedback. Performer facial emotion recognition (Noldus™) was used to assess displayed emotion by the presenters. Mangold VisionPlayer software was used for participant eye movement tracking of the video content. A knowledge survey was created, and Item Content Validity Index (I-CVI) was calculated with a nutrition expert advisory board. Participants were recruited for cognitive interviewing to understand the mental processes and interpretations while answering questions. RESULTS: The video series is available to the public on the Bladder Cancer Advocate Network (BCAN) website at the following URL: https://bcan.org/facing-bladder-cancer/nutrition-bladder-cancer/eating-healthy-bladder-cancer/. Cinematic filming methods, (smaller depth of field, lighting, and camera movement) enhanced message delivery along with music and text on screen to anchor important concepts. CONCLUSIONS: This study can be a framework for the development of a patient education video library accessible through electronic medical records, health care applications, and patient advocacy websites.

Preoperative Optimization of Promotility in Robotic Prostatectomy and Minimally Invasive Kidney Surgery.

INTRODUCTION: Patients are routinely discharged postoperative day 1 following minimally invasive surgery (MIS) for prostate cancer and kidney cancer. Delays in discharge are often related to gastrointestinal symptoms such as nausea, abdominal pain and vomiting; however, the role of baseline constipation in these symptoms and resultant delays in discharge is unclear. We conducted a prospective observational study to describe the incidence of baseline constipation among patients undergoing MIS prostate and kidney surgery, and its relationship to length of stay (LOS). METHODS: Consenting adult patients undergoing MIS procedures for kidney and prostate cancer completed constipation symptom questionnaires perioperatively. Clinicopathological data were collected prospectively. Delay in discharge, defined as LOS >2 days, was the primary outcome. Patients were stratified by the primary outcome and preoperative Patient Assessment of Constipation Symptoms (PAC-SYM) scores were compared. RESULTS: A total of 97 patients enrolled, of whom 29 underwent radical nephrectomy, 34 underwent robotic partial nephrectomy and 34 underwent robotic prostatectomy. Constipation symptoms were reported in 67/97 patients (69%). A total of 17/97 patients (18%) had a delay in discharge. Patients who discharged on time had a median PAC-SYM score of 2 (IQR 2-9) compared to 4 (IQR 0-7.5) for those with a delay (p=0.021). Patients who had a delay with gastrointestinal symptoms had a median PAC-SYM score of 5 (IQR 1.5-11.5, p=0.032). CONCLUSIONS: Seven out of 10 patients undergoing routine MIS procedures report constipation symptoms, which may represent a target for preoperative interventions to reduce LOS after surgery.

Cost Implications of Routine Preoperative Blood Typing and Crossmatching Prior to Robot-Assisted Laparoscopic Partial Nephrectomy.

INTRODUCTION: The surgical treatment of small renal masses has shifted from open to minimally invasive approaches. Preoperative blood typing and product orders often mirror the practices of the open era. We aim to define the rate of transfusion after robot-assisted partial laparoscopic nephrectomy (RAPN) at an academic medical center and the costs associated with current practice. METHODS: A retrospective review of an institutional database was utilized to identify patients who underwent RAPN and transfusion of blood products. Patient, tumor and operative variables were identified. RESULTS: From 2008 to 2021, 804 patients underwent RAPN, with 9 (1.1%) patients requiring a transfusion. Comparison of the transfused group with nontransfused patients yielded a significant difference in mean operative blood loss (527.8 ml vs 162.5 ml, p <0.0001), R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score (7.1 vs 5.9, p <0.05), hemoglobin (11.3 gm/dl vs 13.9 gm/dl, p <0.05) and hematocrit (34.2% vs 41.4%, p <0.05). The variables associated with transfusion on univariate analysis were examined for predictive capacity using logistic regression. Operative blood loss (p <0.05), nephrometry score (p=0.05), hemoglobin (p <0.05) and hematocrit (p <0.05) remained associated with a transfusion. The hospital charge for blood typing and crossmatching was $1,320 USD per patient. CONCLUSIONS: With the maturity of RAPN techniques and outcomes, the extent of preoperative testing related to blood products should evolve to better reflect current procedural risks. Prioritizing testing resources for patients at increased complication risk can be based on predictive factors.

The role of technology in the perioperative management of bladder cancer patients.

Consumer technology in the form of personal computers, mobile devices, and wearable technology, despite current underutilization, has the potential to greatly enhance the practice of urologic oncology and the surgical care of bladder cancer patients, particularly through the dissemination of educational videos, telemedicine, and the use of wearable technology for patient monitoring. A comprehensive healthcare application can unite all of these features, providing curated educational videos at different timepoints in surgical care, facilitating communication between the patient and the care team, and interfacing with wearable technology and other peripherals to allow for nonintrusive patient monitoring to help facilitate early identification of complications and to follow post-operative patient progress. Here we seek to review the available literature on this topic, discuss our institutional experience, and provide future perspectives in the perioperative management of bladder cancer patients.

Factors associated with utilization of neoadjuvant chemotherapy in charlson comorbidity zero non-metastatic muscle-invasive bladder cancer patients

ABSTRACT Background: Guideline-based best practice treatment for muscle invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy (NACRC). Prior studies have shown that a minority of patients receive NACRC and older age and renal function are drivers of non-receipt of NACRC. This study investigates treatment rates and factors associated with not receiving NACRC in MIBC patients with lower comorbidity status most likely to be candidates for NACRC. Materials and Methods: Retrospective United States National Cancer Database analysis from 2006 to 2015 of MIBC patients with Charlson comorbidity index (CCI) of zero. Analysis of NACRC treatment trends in higher CCI patients was also performed. Results: 15.561 MIBC patients met inclusion criteria. 1.507 (9.7%) received NACRC within 9 months of diagnosis. NACRC increased over time (15.0% in 2015 compared to 3.6% in 2006). Higher NACRC was noted in females, cT3 or cT4 cancer, later year of diagnosis, and academic facility treatment. Lower utilization was noted for blacks and NACRC decreased with increasing age and CCI. Only 16.9% of patients aged 23-62 in the lowest age quartile with muscle invasive bladder cancer and CCI of 0 received NACRC. Conclusions: Although utilization is increasing, receipt of NACRC remains low even in populations most likely to be candidates. Further study should continue to elucidate barriers to utilization of NACRC.

Factors associated with utilization of neoadjuvant chemotherapy in charlson comorbidity zero non-metastatic muscle-invasive bladder cancer patients.

BACKGROUND: Guideline-based best practice treatment for muscle invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy (NACRC). Prior studies have shown that a minority of patients receive NACRC and older age and renal function are drivers of non-receipt of NACRC. This study investigates treatment rates and factors associated with not receiving NACRC in MIBC patients with lower comorbidity status most likely to be candidates for NACRC. MATERIALS AND METHODS: Retrospective United States National Cancer Database analysis from 2006 to 2015 of MIBC patients with Charlson comorbidity index (CCI) of zero. Analysis of NACRC treatment trends in higher CCI patients was also performed. RESULTS: 15.561 MIBC patients met inclusion criteria. 1.507 (9.7%) received NACRC within 9 months of diagnosis. NACRC increased over time (15.0% in 2015 compared to 3.6% in 2006). Higher NACRC was noted in females, cT3 or cT4 cancer, later year of diagnosis, and academic facility treatment. Lower utilization was noted for blacks and NACRC decreased with increasing age and CCI. Only 16.9% of patients aged 23-62 in the lowest age quartile with muscle invasive bladder cancer and CCI of 0 received NACRC. CONCLUSIONS: Although utilization is increasing, receipt of NACRC remains low even in populations most likely to be candidates. Further study should continue to elucidate barriers to utilization of NACRC.

Exploration of biomarkers from a pilot weight management study for men undergoing radical prostatectomy.

BACKGROUND: Several biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (CaP) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have CaP recurrence post-prostatectomy. Obesity is related to inflammation and immune dysregulation; thus, weight loss may be an avenue to reduce inflammation and reverse these immune processes. OBJECTIVES: This study explores the reversibility of the biological mechanisms through intentional weight loss using a comprehensive weight management program in men undergoing prostatectomy. Outcomes include blood and tissue biomarkers, microtumor environment gene expression, inflammation markers and Dietary Inflammatory Index (DII) scores. METHODS: Twenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and 5 men chose the nonintervention group. The intervention consisted of a comprehensive weight loss program prior to prostatectomy and a weight maintenance program following surgery. Prostate tissue samples were obtained from diagnostic biopsies before the intervention and prostatectomy samples after weight loss. Blood samples and diet records were collected at baseline, pre-surgery after weight loss and at study end after weight maintenance. Immunohistochemistry and NanoString analysis were used to analyze the tissue samples. Flow cytometry was used to assess circulating immune markers. Inflammation markers were measured using Luminex panels. RESULTS: The intervention group lost >5% body weight prior to surgery. DII scores improved during the weight loss intervention from baseline to pre-surgery (P = 0.002); and between group differences were significant (P = 0.02). DII scores were not associated with IL-6 nor hsCRP. In the intervention, CXCL12, CXCR7, and CXCR4 (C-X-C motif chemokine ligand/receptor) and Ki67 expression decreased in the prostate tissue from biopsy to surgery (P = 0.06), yet plasma CXCL12 increased during the same timeframe (P = 0.009). The downregulation of several genes (FDR<0.001) was observed in the intervention compared to the non-intervention. Changes in immune cells were not significant in either group. CONCLUSION: This feasibility study demonstrates that in overweight men with localized CaP, weight loss alters blood, and tissue biomarkers, as well as tumor gene expression. More research is needed to determine the biological and clinical significance of these findings.

Characterization of perioperative androgen profiles in men with bladder cancer undergoing radical cystectomy.

BACKGROUND: Prior studies have demonstrated declines in androgen levels in men with cancer and patients undergoing anesthesia and surgery. In this study, we hypothesized that decreased serum androgen levels are prevalent in male patients undergoing radical cystectomy (RC) for bladder cancer and that it persists in the postoperative period. We characterized perioperative androgen hormonal profiles and examined for associated changes indicative of sarcopenia on computed tomography scans in men undergoing RC. METHODS: We implemented a prospective observational trial in men with newly diagnosed non-metastatic bladder cancer undergoing RC. Baseline pre-operative total testosterone (TT), free testosterone (FT), and luteinizing hormone (LH) were obtained on morning lab draws with 30 days of surgery. TT and FT were then repeated on postoperative days (POD) 2, 3, 30, and 90. The threshold for normal TT was defined as >300 ng/dl, consistent with the AUA Guidelines for Evaluation and Management of Testosterone Deficiency. We evaluated postoperative changes in weight and psoas muscle cross-sectional area using computed tomography scans to assess for sarcopenic changes. RESULTS: Univariable statistical analysis was performed. 25 patients were enrolled. The mean patient age was 68.9 years. The mean pre-operative TT was 308 ng/dl, and 12/23 (52.5%) patients had low testosterone. Mean TT onPOD 2 and 3 were 166 ng/dl and 161 ng/dl, respectively (range 24-345). 19/20 (95%) of men who had morning lab draws had decreased TT. The mean TT at 30 days was 253 ng/dl with 37.5% of men having low TT. Mean TT at 90 days was 306 ng/dl. The mean FT levels were 43 ng/dl, 29.25 ng/dl, 28.2 ng/dl, 40.89 ng/dl, and 42.62 ng/dl at baseline, POD 2, POD 3, POD 30, and POD 90, respectively. Mean LH at baseline was 9.9 IU/L. Average weight loss at 30- and 90- days postop was -4.29 and -4.38 kilograms, respectively. Weight loss was persistent with only 3/23 (13%) returning to their presurgery weight by 90 days. Despite significant declines in weight and perioperative TT, no significant differences in psoas muscle cross-sectional area were observed (net change -92 mm2, P= 0.13) CONCLUSIONS: Perioperative disruption of androgen levels is prevalent in men undergoing RC. Our trial demonstrates a pre-op, immediate postop, 30- and 90-day postoperative prevalence of low TT of 52%, 95%, 63%, and 37.5%, respectively. Significant changes in baseline weight were noted, although no significant changes in psoas muscle cross-sectional area were observed, limiting conclusions regarding a link between changes in androgens and sarcopenia in this setting.

Feasibility of a Weight Management Program Tailored for Overweight Men with Localized Prostate Cancer - A Pilot Study.

BACKGROUND: Overweight men with prostate cancer are more likely to suffer from recurrence and death following prostatectomy compared with healthy weight men. This study tested the feasibility of delivering a comprehensive program to foster weight loss before and weight maintenance after surgery in overweight men with localized prostate cancer. METHODS: Twenty overweight men scheduled for prostatectomy elected either the intervention (n = 15) or the nonintervention (n = 5). Anthropometrics, biomarkers, diet quality, nutrition literacy, quality of life, and long-term follow-up were assessed in both groups. RESULTS: The intervention led to 5.55 kg of weight loss including 3.88 kg of fat loss from baseline to surgery (mean = 8.3 weeks). The intervention significantly increased fiber, protein, fruit, nut, and vegetable intake; and decreased trans fats intake during weight loss. The intervention significantly reduced insulin, C-peptide, systolic blood pressure, leptin:adiponectin ratio, and visceral adiposity compared to the nonintervention. Post-surgically, weight loss was maintained. Changes in lipid profiles, nutrition literacy, and follow-up were not statistically significant in either group. CONCLUSION: Significant weight loss (≥5%) is feasible with a coaching intervention in overweight men preparing for prostatectomy and is associated with favorable cardiometabolic effects. This study is registered under NCT02252484 (www.clinicaltrials.gov).

Combinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients.

Although biomimetic stimuli, such as microgroove-induced alignment (µ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+)-handling, and molecular analyses. High-resolution optical mapping showed that combined µ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2. 3-, 1. 8-, and 5-fold (>70%), respectively. Such electrophysiological changes could be attributed to an increase in inward sodium current density and a decrease in funny current densities, which is consistent with the observed up- and downregulated SCN1B and HCN2/4 transcripts, respectively. Furthermore, Ca2+-handling transcripts encoding for phospholamban (PLN) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were upregulated, and this led to faster upstroke and decay kinetics of Ca2+-transients. RNA-sequencing and pathway mapping of T3-EC-treated hvCAS revealed that the TGF-ß signaling was downregulated; the TGF-ß receptor agonist and antagonist TGF-ß1 and SB431542 partially reversed T3-EC induced quiescence and reduced spontaneous contractions, respectively. Taken together, we concluded that topographical cues alone primed cardiac tissue constructs for augmented electrophysiological and calcium handling by T3-EC. Not only do these studies improve our understanding of hPSC-CM biology, but the orchestration of these pro-maturational factors also improves the use of engineered cardiac tissues for in vitro drug screening and disease modeling.

The Limited Usefulness of Ultrasound Surveillance after Radical and Partial Nephrectomy for Renal Cell Carcinoma.

INTRODUCTION: We determined the usefulness of ultrasound compared to cross-sectional imaging in the detection of intra-abdominal recurrences after radical or partial nephrectomy for localized renal cell carcinoma. METHODS: We performed a retrospective review of 800 patients with clinically localized renal cell carcinoma who had undergone radical or partial nephrectomy between 2008 and 2015. Patients had at minimum 1 year of followup at our institution, at least 1 ultrasound during surveillance and no metastases at time of surgery. Our primary outcome was the rate of diagnosis of abdominal recurrence based on modality of surveillance. RESULTS: Median followup for the entire cohort was 37.5 months (range 12 to 166). Overall 396 and 404 patients underwent radical and partial nephrectomy, respectively, for localized renal cell carcinoma. There were 224 (57%) and 234 (58%) patients in the radical and partial nephrectomy cohorts, respectively, who had 2 or more ultrasounds performed during surveillance. In the radical and partial nephrectomy cohorts a total of 149 (19%) abdominal recurrences were detected, with only 8 (19%) initially detected by ultrasound. On the other hand, 15 (10%) recurrences were missed by a prior negative ultrasound. Furthermore, there were 8 false-positive ultrasound studies that cross-sectional imaging later ruled out. CONCLUSIONS: The low yield of ultrasound in the detection of abdominal recurrences after radical or partial nephrectomy for renal cell carcinoma raises questions as to its usefulness in routine surveillance.

Glycemic impact of a diet and lifestyle intervention on diabetics and prediabetics during treatment for non-muscle invasive bladder cancer.

Introduction: Patients with Type II Diabetes Mellitus (DM2) have increased risk of recurrence and progression of non-muscle invasive bladder cancer (NMIBC). Glucose control through lifestyle intervention is an uninvestigated, attractive strategy to decrease risk of cancer recurrence. We test the feasibility of a diet and exercise program and its glycemic impact in patients with DM2 and NMIBC.Materials/methods: Five participants with NMIBC and pre-diabetes or DM2 were recruited for a pilot, prospective clinical trial. Each participant received dietary counseling for 16 sessions during clinical visits. The intervention included a carbohydrate-restricted (CR) diet (<130 grams per day), 30 min, walking 5×/wk, and 5000 steps daily. Diet compliance was measured with 24-hour diet recall. Exercise was monitored with accelerometer and self-report.Results: Five participants enrolled and two participants completed the 12-month intervention. Adherence was 60% to CR diet and 84% to exercise goals. Participants reduced carbohydrate consumption by 44%. Participants showed reductions in fasting blood glucose, HbA1c, glucosuria, fasting blood insulin, and body weight, and increased euglycemia on continuous glucose monitoring.Conclusions: Adherence to a CR diet and exercise goals is feasible in patients with NMIBC and DM2 and also leads improved glucose control. A phase-II trial on bladder cancer-specific outcomes is warranted.

Tumor M2-PK: A novel urine marker of bladder cancer.

PURPOSE: Bladder cancer is a "Warburg-like" tumor characterized by a reliance on aerobic glycolysis and expression of pyruvate kinase M2 (PKM2). PKM2 oscillates between an active tetramer and an inactive dimer. We aim to further characterize PKM2, in particular PKM2 dimer, as a urinary biomarker of bladder cancer and a potential target for treatment. METHODS: HTB-9, HTB-5, and UM-UC3 bladder cancer cells were assessed for proliferation under differential glucose levels using the hexosaminidase assay. Western blot and Blue-native analysis was performed for protein expression of PKM2. Shikonin, an herb that is known to bind and inhibit PKM2, was utilized to determine if PKM2 has a role in glucose usage and cellular proliferation in bladder cancer cells by caspase activity assay. Institutional review board approval was obtained to collect healthy control and bladder cancer patient urine samples. The ScheBo M2-PK EDTA Plasma Test was performed on urine samples to assess urine Tumor M2-PK values. RESULTS: The three bladder cancer cell lines tested all demonstrate statistically significant increases in proliferation when exposed to higher level of glucose (200mg/dL). Similarly, low doses of glucose (25mg/dL) result in reduced proliferation. Increased cell growth in higher glucose concentration correlated with up-regulation of PKM2 protein expression. Shikonin, a PKM2 inhibitor, reduced cell proliferation and switched PKM2 isoforms from the dimer to tetramer. Lastly, dimer PKM2 (Tumor-M2PK) levels were assessed in the urine samples from bladder cancer (Bca) patients and healthy controls. Tumor M2-PK significantly correlated with the presence of BCa in our subjects. CONCLUSIONS: Our studies demonstrate the potential of PKM2, specifically the dimer (Tumor-M2PK) as a target of drug therapy and as a urinary marker for bladder cancer.

Systematic Review of Factors Associated with the Utilization of Radical Cystectomy for Bladder Cancer.

CONTEXT: Despite established guidelines for the treatment of muscle-invasive bladder cancer, it has been reported that radical cystectomy (RC) is markedly underused, especially among patients of advanced age and those with higher comorbidity burden and lower access to care. Understanding the interactions between patient, provider, and hospital factors may inform targeted interventions to optimize RC utilization. OBJECTIVE: To systematically review the literature regarding factors associated with RC utilization. EVIDENCE ACQUISITION: A systematic search was conducted using Ovid and Medline according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2017 reporting on RC utilization. Prospective and retrospective studies were included. EVIDENCE SYNTHESIS: There are no published randomized control trials on RC utilization. Variations in study quality and design precluded a formal statistical meta-analysis. RC receipt significantly depended on patient, provider, and hospital factors. Patient factors associated with lower RC use included advanced age, African American and Hispanic race/ethnicity, higher comorbidity burden, unmarried marital status, higher tumor stage and grade, and lower socioeconomic status. Provider factors associated with underutilization included lower surgeon volume and a metropolitan location. Finally, hospital factors associated with lower RC use included low hospital volume, nonacademic affiliation, and hospital location in the Midwest. CONCLUSIONS: RC is reportedly underutilized. We found that age, race, marital status, socioeconomic factors, cancer severity, comorbidity burden, surgeon volume, and facility type and location significantly determined RC receipt. Improved understanding of the varying contributions of the risk factors according to patient, provider, and hospital determinants may assist in developing targeted interventions to improve RC utilization. PATIENT SUMMARY: In this review we explored the clinical evidence for factors predicting the utilization of radical cystectomy for muscle-invasive bladder cancer. Many factors related to the patient, provider, and hospital determine whether patients receive this guideline-recommended treatment. However, there remains a lack of understanding on characterization and targeted interventions according to these levels, which may improve use.

Human Cardiac Ventricular-Like Organoid Chambers and Tissue Strips From Pluripotent Stem Cells as a Two-Tiered Assay for Inotropic Responses.

Traditional drug discovery is an inefficient process. Human pluripotent stem cell-derived cardiomyocytes can potentially fill the gap between animal and clinical studies, but conventional two-dimensional cultures inadequately recapitulate the human cardiac phenotype. Here, we systematically examined the pharmacological responses of engineered human ventricular-like cardiac tissue strips (hvCTS) and organoid chambers (hvCOC) to 25 cardioactive compounds covering various drug classes. While hvCTS effectively detected negative and null inotropic effects, the sensitivity to positive inotropes was modest. We further quantified the predictive capacity of hvCTS in a blinded screening, with accuracies for negative, positive, and null inotropic effects at 100%, 86%, and 80%, respectively. Interestingly, hvCOC, with a pro-maturation milieu that yields physiologically complex parameters, displayed enhanced positive inotropy. Based on these results, we propose a two-tiered screening system for avoiding false positives and negatives. Such an approach would facilitate drug discovery by leading to better overall success.

The Feasibility of a Health Care Application in the Treatment of Patients Undergoing Radical Cystectomy.

PURPOSE: Patients who undergo radical cystectomy of bladder cancer are at high risk for complications and hospital readmissions. Studies indicate insufficient preoperative education and perioperative monitoring. The aim of this study was to demonstrate the feasibility of implementing a health care application to provide more patient education and more thorough monitoring perioperatively. MATERIALS AND METHODS: Participants with home Wi-Fi access who were undergoing radical cystectomy were recruited for this pilot trial. Each subject was provided a tablet preloaded with the m.Care (LifeScience Technologies, Leawood, Kansas) health care application, an accelerometer and vital sign equipment. Participants were asked to watch educational videos, use the provided accelerometer and perform vital sign monitoring. RESULTS: In 1 year 20 participants enrolled in the study and 15 completed it. The most frequently viewed videos were "Ileal Conduit versus Neobladder" and "Comprehensive Care Pathway." All participants used the accelerometer and 60% kept up with syncing the data regularly. The average step count preoperatively was 5,679 reflecting a sedentary population. Step counts decreased during the inpatient stay (1,351 steps) and trended toward baseline during the postoperative period (3,156 steps). Vital signs were recorded on 85% of assigned days and generated 33 triggers for intervention. While most triggers led to repeat assessment, education and encouragement, 4 participants underwent outpatient treatment, including cultures, intravenous fluids, antibiotics or dronabinol prescription, without the need for hospital readmission. CONCLUSIONS: Providing more education and monitoring perioperatively is feasible using a health care application. Testing is warranted to determine the extent to which implementation will improve patient triaging and reduce readmissions.

Contemporary Preoperative and Intraoperative Management of the Radical Cystectomy Patient.

Radical cystectomy is a morbid procedure performed on an aging and often frail population. Nonetheless, advances in preoperative and intraoperative management have significantly improved patient outcomes. Preoperative optimization includes a focus on patient education, risk factor reduction, risk stratification, nutritional optimization, and bowel motility enhancement. Intraoperative optimization focuses on maintaining normothermia, restrictive fluid administration, minimization of blood transfusions, and nonopioid pain management.

Postoperative Outcomes After Radical Cystectomy in Patients With Prior Pelvic Radiation.

OBJECTIVE: To compare complication rates, perioperative outcomes, and survival after radical cystectomy (RC) in patients with prior abdominal or pelvic radiation therapy (RT) vs those without an RT history. MATERIALS AND METHODS: We retrospectively reviewed patients undergoing RC for urothelial carcinoma between January 2008 and January 2016. Patients were stratified by receipt of RT, and differences in complications (any, minor, and major) at 30 and 90 days, as well as estimated blood loss, length of surgery, length of hospital stay, and pathologic stage, were compared. Recurrence-free, cancer-specific, and overall survival were compared using the Kaplan-Meier method and log-rank test. RESULTS: We identified 518 patients who underwent RC between 2008 and 2016. Of these patients, 55 (11%) had a history of RT. There were no significant differences in complication rates (66% vs 69%, P= .80) between patients who did not and patients who did have a history of RT. Similarly, there were no differences in any perioperative or pathologic outcome by receipt of prior RT (all P>.05). Meanwhile, at a median follow-up of 26 (interquartile range 13-46) months among patients alive at last follow-up, no differences in survival were observed by prior RT (P= .08). CONCLUSION: Among patients with a history of prior abdominal or pelvic RT treated at a tertiary referral center, there was no difference in complication rates, perioperative, or pathologic outcomes. Importantly, no differences in survival were noted by prior RT receipt. Therefore, our data support the use of RC, when indicated, in patients with a prior history of abdominal or pelvic RT.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.

PURPOSE: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS: In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS: Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.