The Impact of Omission of Intraoperative Frozen Section Prior to Orthotopic Neobladder Reconstruction.

PURPOSE: Current guidelines recommend confirming a negative urethral margin prior to orthotopic neobladder reconstruction. We investigated our rate of urethral positive margins and recurrence in the absence of intraoperative frozen section. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on 357 patients who underwent radical cystectomy and orthotopic urinary diversion without intraoperative frozen section. At a median followup of 27 months the rates of positive urethral margins and urethral recurrence were tabulated. Differences in overall and recurrence-free survival in patients with a positive urethral margin were analyzed by Cox regression to generate the HR with the 95% CI. RESULTS: We identified 6 urethral recurrences (1.6%) during followup. The urethral recurrence rate was not higher in patients with a positive urethral margin (p=0.22). In the 15 patients with positive urethral margins overall survival was unchanged (HR 0.98, 95% CI 0.24-4.04). When accounting for lymph node staging, recurrence-free survival was not significantly worse in patients with positive urethral margins (HR 2.33, 95% CI 0.95-5.73). CONCLUSIONS: Omitting intraoperative frozen section prior to orthotopic neobladder reconstruction appears safe with a rate of urethral recurrence similar to that in historical series. It may allow for increased performance of orthotopic urinary diversions.

Emerging therapies in the management of high-risk non-muscle invasive bladder cancer (HRNMIBC).

PURPOSE: BCG is the gold standard in management of high-risk non-muscle invasive bladder cancer (HRNMIBC). However, in patients who fail BCG, there are few effective intrasvesical options. This review aims to explore standard and emerging therapies in HRNMIBC. METHODS: A non-systematic literature review was performed using Medline and PubMed. Literature focused on HRNMIBC and BCG failure studies, with particular attention to Phase II and III clinical trials. RESULTS: The only FDA approved therapy for BCG failure patients in Valrubicin. Patients with HRNMIBC and BCG failure patients are at increased risk for progression and death from bladder cancer. There are a variety of clinical trials exploring different therapeutic approaches such as immunotherapy, vaccines, radiotherapy, and gene therapy. These trials are showing some promise in the early reporting phase. CONCLUSION: Despite limited intravesical treatment options in BCG failure patients, there are several promising therapies currently being developed and several with promising early results.

Current Clinical Trials in Non-muscle-Invasive Bladder Cancer: Heightened Need in an Era of Chronic BCG Shortage.

PURPOSE OF REVIEW: BCG is the gold standard agent used in high-risk non-muscle-invasive bladder cancer (NMIBC) that is amenable to bladder sparing management. However, recent BCG shortages appear to be a chronic problem. There are limited effective intravesical options in lieu of BCG or in patients in whom BCG is not effective. This review aims to highlight emerging bladder sparing therapies and trials for NMIBC. RECENT FINDINGS: Patients with high-risk NMIBC who do not respond to BCG are at increased risk for progression and death from bladder cancer. There are a variety of clinical trials exploring different therapeutic approaches including checkpoint inhibition, novel chemotherapy and drug delivery, viral and gene therapy, vaccines, and targeted therapy. In the era of limited supply of BCG, there is a need for both effective first-line alternatives as and options for patients who do not respond to BCG. Fortunately, there are a variety of active trials and mechanisms exploring these areas aggressively.

Novel focal therapy treatment options for prostate cancer.

PURPOSE OF REVIEW: Examine and discuss novel focal therapy treatment options for prostate cancer. RECENT FINDINGS: With the widespread adoption of mpMRI-guided biopsies for prostate cancer, use of image-guided treatment of prostate cancer has increased. Focal therapies leading to partial gland ablation such as partial prostatectomy, focal laser ablation, irreversible electroporation, vascular targeted photodynamic therapy, and focal radiofrequency ablation have emerged and begun to be properly evaluated. This review covers published phase 1 and 2 trials of each treatment and discusses potential limitations of each modality. SUMMARY: Focal therapy of prostate cancer is being actively investigated. On the basis of limited published data, the treatments appear to be well tolerated and have an acceptable side effect profile. Importantly, short-term oncologic control has been mixed and there are no long-term outcomes. The acquisition of more data is essential to evaluate these novel technology platforms.

Indications, evolving technique, and early outcomes with robotic retroperitoneal lymph node dissection.

PURPOSE OF REVIEW: Examine and discuss indications, technique, and outcomes for robotic retroperitoneal lymph node dissection (RPLND) for testicular cancer. RECENT FINDINGS: Open RPLND has been the longstanding standard of care for both primary and post chemotherapy RPLND. Recently, robotic RPLND has been an attractive option with the intent of reducing the morbidity associated with open surgery while providing identical oncologic efficacy. Naysayers of robotic RPLND suggest it is often inappropriately used as a staging procedure and consequently can compromise oncologic efficacy. SUMMARY: Robotic RPLND is being evaluated as a therapeutic equivalent to open RPLND. On the basis of limited published data with modest follow-up from experienced centers, robotic RPLND appears to provide effective staging and therapeutic data mirroring that of open surgery.

Necrotizing Fasciitis of the Hand After a Prolonged Endodontic Procedure: A Case Report.

CASE: In this article, we present a case report of a patient with limited medical history and without apparent local injury, who developed left hand Group A Streptococcus-induced necrotizing fasciitis after undergoing a prolonged endodontic procedure. CONCLUSION: In addition to host factors, perhaps, the virulence of the bacteria present in the oropharynx and the expected bacterial load based on the length and complexity of a dental procedure need to be considered when deciding on whether or not to administer prophylactic antibiotics to patients undergoing dental procedures.

Flexor Carpi Radialis Brevis Resection for Treatment of a Distal Radius Fracture: A Case Report.

The flexor carpi radialis brevis (FCRB) is an anomalous muscle of the forearm that is only present in 3.5 to 8.6% of the population. In the case of volar plating of distal radius fractures, the FCRB inhibits proper fracture exposure and thus hinders proper reduction. A 78-year-old female presented with right distal radius fracture which necessitated internal fixation. Following mobilization and retraction of the flexor carpi radialis tendon, an anomalous muscle belly was identified as the FCRB. With continued difficulty in exposure and fracture site reduction, resection of the FCRB was performed. The patient was able to return to her activities of daily living without pain and demonstrated no appreciable functional deficit. This case report demonstrates a distal radius fracture where FCRB resection was used, resulting in no detrimental clinical outcomes.

The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis.

INTRODUCTION: While numerous current clinical trials are testing novel salvage therapies (ST) for patients with recurrent nonmuscle invasive bladder cancer (NMIBC) after bacillus Calmette-Guérin (BCG), the natural history of this disease state has been poorly defined to date. Herein, we evaluated oncologic outcomes in patients previously treated with BCG and ST who subsequently underwent radical cystectomy (RC). METHODS: We identified 378 patients with high-grade NMIBC who received at least one complete induction course of BCG (n = 378) with (n = 62) or without (n = 316) additional ST and who then underwent RC between 2000 and 2018. Oncologic outcomes were compared using the Kaplan-Meier method and Cox proportional hazards models. Sensitivity analyses were conducted stratifying by presenting tumor stage, matched 1:3 for receipt vs. no receipt of ST. RESULTS: Patients receiving ST were more likely to initially present with CIS (26% vs. 17%) and less likely with T1 disease (34% vs. 50%, P = 0.06) compared to patients not treated with ST. Receipt of ST was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (31% vs. 41%, P = 0.14). Likewise, 5-year cancer-specific survival did not significantly differ between groups on univariable Kaplan-Meier analysis (73% for ST and 74% for no ST, P = 0.7). Moreover, on multivariable analysis, receipt of ST was not significantly associated the risk of death from bladder cancer (HR 1.12; 95% CI 0.60-2.09, P = 0.7). Results were unchanged on sensitivity analysis. CONCLUSIONS: These data suggest that, in carefully selected patients, ST following BCG for high grade NMIBC does not compromise oncologic outcomes for patients who ultimately undergo RC.

Defining risk of micrometastatic disease and tumor recurrence in patients with stage I testicular germ cell tumors.

There is controversy in the management of patients with clinical stage I non-seminomatous germ cell tumor (NSGCT). Some experts recommend surveillance for all patients regardless of risk factors while others suggest a more risk-adapted approach by using lymphovascular invasion (LVI) and the embryonal component in the primary tumor to select patients most likely to benefit from primary treatment [retroperitoneal lymph node dissection (RPLND) or chemotherapy]. With the surveillance for all strategy, only patients who relapse are treated. While this minimizes the over treatment, problem associated with the risk adapted approach, this exposes young men to the effects of full induction cisplatin-based chemotherapy when these men could have received fewer cycles of bleomycin, etoposide, and cisplatin (BEP) or a curative primary RPLND. The challenge is identifying these men who are most likely to benefit from upfront treatment more precisely. This paper explores the currently risk adapted approaches as well as promising emerging biomarkers (microRNA) that, in early data, appear to more accurately predict the presence of microscopic disease in the retroperitoneum over conventional markers.

The Impact of Lymphovascular Invasion on Risk of Upstaging and Lymph Node Metastasis at the Time of Radical Cystectomy.

BACKGROUND: Lymphovascular invasion (LVI) in muscle-invasive bladder cancer is associated with a poor prognosis when identified from radical cystectomy (RC) specimens. However, LVI is not clearly emphasized in any risk models to guide clinical decision-making. The impact of LVI on the risk of lymph node (LN) metastasis after a transurethral resection of bladder tumor (TURBT) specimen is less understood. OBJECTIVE: The goal was to describe the impact of LVI and the risk of LN metastasis at each clinical stage of urothelial carcinoma of the bladder (UC). DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Database was queried for patients with bladder cancer who underwent RC with LN dissection from 2004 to 2014. Patients with non-bladder primary, non-UC histology, clinical metastatic disease, and having received chemotherapy/radiation were excluded. Pathologic LN positive rates at RC were determined. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic upstaging at RC and pathologic node positivity. Secondary outcomes included determining overall survival (OS). All hypotheses testing were two-sided and a p value of <0.05 was considered statistically significant. All statistical analyses were performed using Stata version 13.1. RESULTS AND LIMITATIONS: A total of 3007 patients with UC underwent RC with pelvic LN dissection. In patients with LVI, the risk of LN metastasis was significantly higher at each clinical stage as was the rate of pathologic upstaging. Patients with LVI on TURBT had worse OS stage for stage in pure UC (p<0.001). Limitations include that there was no central pathologic review and the number of TURBTs per patient was not known. CONCLUSIONS: Patients with UC with LVI had worse OS and are at higher risk for LN-positive disease and pathologic upstaging at surgery than patients without LVI. PATIENT SUMMARY: In this report we examined the impact of lymphovascular invasion (LVI) at transurethral resection of bladder tumor on pathologic upstaging and lymph node metastasis at radical cystectomy using the National Cancer Database. We identified LVI as being prognostic at each stage of urothelial carcinoma.

Transurethral resection and surveillance of a well-differentiated neuroendocrine tumor in a ileal neobladder.

Our patient presented with a small, well-differentiated neuroendocrine tumor (NET) of the ileal neobladder 21-years after radical cystectomy for urothelial cell carcinoma. Given the rarity of NETs in urinary diversions, there are no established guidelines regarding management in this unique population. We propose that transurethral resection and close cystoscopic surveillance of the neobladder is a feasible, low morbidity approach to management of a well-differentiated, solitary ileal NET tumor.

A rare case of pancreatic adenocarcinoma metastasized to the bladder.

Pancreatic cancer is usually detected in late stages due to lack of identifiable symptoms and rapid progression. It commonly metastasizes to the liver, lung, and peritoneum, but only rarely to the bladder. We present a 41-year-old female with a history of pancreatic adenocarcinoma, asthma, gastroesophageal reflux disease, uterine fibroids, and tobacco use who presented with hematuria, polyuria, and abdominal pain. The CT showed bilateral hydroureteronephrosis with a hyperdense region in the posterior wall of the bladder. Pathology revealed metastatic pancreatic adenocarcinoma to the bladder. This is the fourth reported case of pancreatic adenocarcinoma metastasizing to the bladder since 1953.

National management trends in clinical stage IIA nonseminomatous germ cell tumor (NSGCT) and opportunities to avoid dual therapy.

INTRODUCTION: For marker-negative clinical stage (CS) IIA nonseminomatous germ cell tumor (NSGCT), National Comprehensive Cancer Network and American Urological Association guidelines recommend either retroperitoneal lymph node dissection (RPLND) or induction chemotherapy. The goal is cure with one form of therapy. We evaluated national practice patterns in the management of CSIIA NSGCT and utilization of secondary therapies. METHODS: The National Cancer Data Base was used to identify 400 men diagnosed with marker negative CSIIA NSGCT between 2004 and 2014 treated with RPLND or chemotherapy. Trends in the utilization of initial and adjuvant treatment (chemotherapy only, RPLND only, RPLND with adjuvant chemotherapy, and postchemotherapy RPLND) were analyzed. RESULTS: Of the 400 cases, 233 (58%) underwent induction chemotherapy with surveillance, 51 (20%) underwent RPLND with surveillance, 89 (22%) underwent RPLND followed by adjuvant chemotherapy, and 14 (4%) underwent induction chemotherapy followed by RPLND. Thirty percent of patients received dual therapy. After RPLND with pN1 staging, 43 (61%) underwent adjuvant chemotherapy. The pN0 rate after primary RPLND was 22%. Five year overall survival ranged from 95% to 100% based on initial treatment choice. CONCLUSIONS: For marker negative CS IIA nonseminoma, dual, therapy, and treatment with chemotherapy is common. With low volume retroperitoneal disease resected at RPLND, adjuvant chemotherapy was frequently administered but has debatable therapeutic value. These data highlight opportunities to decrease treatment burden in patients with CS IIA nonseminoma.

The impact of surgical duration on complications after transurethral resection of the prostate: an analysis of NSQIP data.

BACKGROUND: Transurethral resection of the prostate is the most commonly performed procedure for the management of benign prostatic obstruction. However, little is known about the effect surgical duration has on complications. We assess the relationship between operative time and TURP complications using a modern national surgical registry. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2006 to 2016 for patients undergoing TURP. Patients were separated into five groups based on operative time: 0-30 min, 30.1-60 min, 60.1-90 min, 90.1-120 min, and greater than 120 min. Standard statistical analysis, including multivariate regression, was performed to determine factors associated with complications. RESULTS: 31,813 patients who underwent TURP were included. The overall complication rate was 9.0% and increased significantly with longer surgical duration (p < 0.001). Longer operative time was associated with a greater risk of postoperative sepsis or shock, transfusion, reoperation, and deep vein thrombus or pulmonary embolism. Longer surgical duration was associated with increased odds of any complication and, specifically, blood transfusion after controlling for age, race, comorbidities, American Society of Anesthesia (ASA) class, type of anesthesia administered, and trainee involvement. The adjusted risk of each of the above complications remained significantly increased for surgeries lasting longer than 120 min. CONCLUSIONS: As surgical duration increases, there is a significant increase in the rate of complications after TURP. These data demonstrate that this procedure is safest when performed in under 90 min.

Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy.

BACKGROUND: Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor. We characterized the tumor microenvironment within the responding and non-responding tumors. CASE PRESENTATION: A 54-year-old female was diagnosed with a locally advanced clear cell renal cell carcinoma with a level IV tumor thrombus of the vena cava. She was initially deemed unfit for surgical resection due to poor performance status. She underwent neoadjuvant immunotherapy with nivolumab and ipilimumab with a complete response of the vena cava and renal vein tumor thrombus, but had stable disease within her renal mass. She underwent complete surgical resection with negative margins and remains disease-free longer than 1 year after her diagnosis with no further systemic therapy. Notably, pathologic analysis showed a complete response within the vena cava and renal vein, but substantial viable cancer remained in the kidney. Multichannel immunofluorescence was performed and showed marked infiltration of immune cells including CD8+ T cells and Batf3+ dendritic cells in the thrombus, while the residual renal tumor showed a non-T cell-inflamed phenotype. CONCLUSIONS: Preoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis.

Eligibility and Radiologic Assessment in Adjuvant Clinical Trials in Bladder Cancer.

Objective: To harmonize eligibility criteria and radiographic disease assessments in clinical trials of adjuvant therapy for muscle-invasive bladder cancer (MIBC). Methods: National experts in bladder cancer clinical trial research, including medical and urologic oncologists, radiologists, biostatisticians, and patient advocates, convened at a public workshop on November 28, 2017, to discuss eligibility, radiographic entry criteria, and assessment of disease recurrence in adjuvant clinical trials in patients with MIBC. Results: The key workshop conclusions for adjuvant MIBC clinical trials included the following points: (1) patients with urothelial carcinoma with divergent histologic differentiation should be allowed to enroll; (2) neoadjuvant chemotherapy is defined as at least 3 cycles of neoadjuvant cisplatin-based combination chemotherapy; (3) patients with muscle-invasive, upper-tract urothelial carcinoma should be included in adjuvant trials of MIBC; (4) patients with severe renal insufficiency can enroll into trials using agents that are not renally excreted; (5) patients with microscopic surgical margins can be included; (6) patients should undergo a standard bilateral lymph node dissection prior to enrollment; (7) computed tomographic (CT) imaging should be performed within 4 weeks prior to enrollment. For patients with renal insufficiency who cannot undergo CT imaging with contrast, noncontrast chest CT and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be done; (8) biopsy of indeterminate lesions to evaluate for malignant disease should be done when feasible; (9) a uniform approach to evaluate indeterminate radiographic lesions when biopsy is not feasible should be included in any trial design; (10) a uniform approach to determining the date of recurrence is important in interpreting adjuvant trial results; and (11) new high-grade, upper-tract primary tumors and new MIBC tumors should be considered recurrence events. Conclusions and Relevance: A uniform approach to eligibility criteria, definitions of no evidence of disease, and definitions of disease recurrence may lead to more consistent interpretations of adjuvant trial results in MIBC.

Testicular Cancer: Epidemiology, Diagnosis, and Management.

There were an estimated 8720 new cases of testicular cancer (TC) in the United States in 2016. The cause of the disease is complex, with several environmental and genetic risk factors. Although rare, the incidence has been steadily increasing. Fortunately, substantial advances in treatment have occurred over the last few decades, making TC one of the most curable malignancies. However, because TC typically occurs in younger men, considerations of the treatment impact on fertility, quality of life, and long-term toxicity are paramount; an individualized approach must be taken with patients based on their clinical and pathologic findings.