From Detection to Cure - Emerging Roles for Urinary Tumor DNA (utDNA) in Bladder Cancer.

PURPOSE OF REVIEW: This review sought to define the emerging roles of urinary tumor DNA (utDNA) for diagnosis, monitoring, and treatment of bladder cancer. Building from early landmark studies the focus is on recent studies, highlighting how utDNA could aid personalized care. RECENT FINDINGS: Recent research underscores the potential for utDNA to be the premiere biomarker in bladder cancer due to the constant interface between urine and tumor. Many studies find utDNA to be more informative than other biomarkers in bladder cancer, especially in early stages of disease. Points of emphasis include superior sensitivity over traditional urine cytology, broad genomic and epigenetic insights, and the potential for non-invasive, real-time analysis of tumor biology. utDNA shows promise for improving all phases of bladder cancer care, paving the way for personalized treatment strategies. Building from current research, future comprehensive clinical trials will validate utDNA's clinical utility, potentially revolutionizing bladder cancer management.

The Impact of Ureteral Access Sheath Use on the Development of Abnormal Postoperative Upper Tract Imaging after Ureteroscopy.

PURPOSE: Ureteral access sheaths are commonly used during ureteroscopy to facilitate stone removal, improve visibility and maintain low intrarenal pressures. However, the use of a ureteral access sheath can cause ureteral wall ischemia and ureteral tears, potentially increasing the risk of postoperative ureteral stricture and obstruction. We studied the impact of ureteral access sheath use on postoperative imaging studies. Secondary objectives included studying the impact of other intraoperative parameters on postoperative imaging studies. MATERIALS AND METHODS: A retrospective chart review was conducted of cases that underwent ureteroscopy for nephroureterolithiasis across 2 high volume institutions between January 2012 and September 2016. Patient demographics, cumulative stone size, operative time, use of ureteral access sheath, laser lithotripsy, basket extraction, preoperative ureteral stent and postoperative ureteral stent placement were extracted from the electronic medical record. Findings of followup renal ultrasound, kidney-ureter-bladder x-ray and/or computerized tomography at approximately 8 weeks after surgery were recorded. RESULTS: A total of 1,332 ureteroscopies were performed with 1,060 cases (79.6%) returning for routine upper tract imaging after ureteroscopy. Postoperative hydronephrosis was noted following 127 cases (12.0%). Factors predicting presence of hydronephrosis after ureteroscopy include lower body mass index (p=0.0016), greater cumulative stone size (p=0.0003), increased operative time (p <0.0001), preoperative ureteral stent (OR 1.49, p=0.0299) and postoperative ureteral stent placement (OR 6.43, p=0.0031). Postoperative hydronephrosis was not associated with use of ureteral access sheath, age, laser lithotripsy or basket extraction. CONCLUSIONS: Use of ureteral access sheath did not have a significant impact on development of postoperative hydronephrosis, suggesting ureteral access sheath is safe for use during ureteroscopy. Ureteral strictures remain rare following ureteroscopy, seen in only 1.0% of our cohort. With an observed prevalence of hydronephrosis of 12.0% on followup imaging at 8 weeks, routine upper tract imaging after ureteroscopy remains a valuable prognostic tool.

Multiplex Immunofluorescence Captures Progressive Immune Exhaustion with Advancing Penile Squamous Cell Cancer Stage.

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status.

Succinate dehydrogenase deficient renal cell carcinoma: A case report.

Succinate dehydrogenase (SDH) deficient renal cell carcinoma (RCC) are uncommon renal tumors that typically present in relatively younger patients. SDH mutations are known to cause cancer, but often presents with hereditary paragangliomas, pheochromocytomas, and gastrointestinal stromal tumors. This report details a case of SDH deficient RCC in a patient with no know contributing family history. Patient presented with recurrent urinary tract infections and groin pain. Computerized tomography (CT) revealed a 4 cm mass in the right kidney. Partial nephrectomy was performed, and the patient had an uneventful recovery. Immunohistochemical staining revealed the tumor was SDH negative.

Predicting Complete Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

Muscle-invasive bladder cancer is a life-threatening disease best managed with multimodal therapy. Neoadjuvant chemotherapy prior to cystectomy significantly improves survival with the greatest benefit noted in patients with a complete pathologic response noted at cystectomy. While radical cystectomy is currently an important part of the treatment plan, surgical morbidity remains high. Accurate prediction of complete responses to chemotherapy would enable avoiding the morbidity of radical cystectomy. Multiple clinical, pathologic, molecular, and radiographic predictors have been evaluated. Clinical and standard pathologic findings have not been found to be accurate predictors of complete response. To date, tumor genomic findings have been the most promising and have led to multiple clinical trials to evaluate if bladder preservation is possible in select patients. Radiomics has shown initial promise with larger validation series needed. These predictors can be further characterized as treatment specific and non-treatment specific. With the potential changing landscape of neoadjuvant therapy prior to radical cystectomy and the limitations of individual predictors of a complete response, a panel of several biomarkers may enhance patient selection for bladder preservation. The aim of this review is to summarize predictors of complete response to neoadjuvant chemotherapy.

Are there Field Triage Criteria that Can Predict Low-Yield Air Medical Transports?

INTRODUCTION: Air medical transport of trauma patients from the scene of injury plays a critical role in the delivery of severely injured patients to trauma centers. Over-triage of patients to trauma centers reduces the system efficiency and jeopardizes safety of air medical crews. HYPOTHESIS: The objective of this study was to determine which triage factors utilized by Emergency Medical Services (EMS) providers are strong predictors of early discharge for trauma patients transported by helicopter to a trauma center. METHODS: A retrospective chart review over a two-year period was performed for trauma patients flown from the injury site into a Level I trauma center by an air medical transport program. Demographic and clinical data were collected on each patient. Prehospital factors such as Glasgow Coma Score (GCS), Revised Trauma Score (RTS), intubation status, mechanism of injury, anatomic injuries, physiologic parameters, and any combinations of these factors were investigated to determine which triage criteria accurately predicted early discharge. Hospital factors such as Injury Severity Score (ISS), length-of-stay (LOS), survival, and emergency department disposition were also collected. Early discharge was defined as a hospital stay of less than 24 hours in a patient who survives their injuries. A more stringent definition of appropriate triage was defined as a patient with in-hospital death, an ISS >15, those taken to the operating room (OR) or intensive care unit (ICU), or those receiving blood products. Those patients who failed to meet these criteria were also used to determine over-triage rates. RESULTS: An overall early discharge rate of 35% was found among the study population. Furthermore, when the more stringent definition was applied, over-triage rates were as high as 85%. Positive predictive values indicated that patients who met at least one anatomic and physiologic criteria were appropriately transported by helicopter as 94% of these patients had stays longer than 24 hours. No other criteria or combination of criteria had a high predictive value for early discharge. CONCLUSIONS: No individual triage criteria or combination of criteria examined demonstrated the ability to uniformly predict an early discharge. Although helicopter transport and subsequent hospital care is costly and resource consuming, it appears that a significant number of patients will be discharged within 24 hours of their transport to a trauma center. Future studies must determine the impact of eliminating "low-yield" triage criteria on under-triage of scene trauma patients.