The Association Between Duration of Antibiotics and Infectious Complications Following Radical Cystectomy: Analysis of the 2019-2021 NSQIP Database.

OBJECTIVES: To identify the impact of the duration of peri-operative antibiotics on infectious complications following radical cystectomy. METHODS: The National Surgical Quality Improvement Project (NSQIP) targeted database was queried for patients undergoing radical cystectomy from 2019 to 2021. Baseline patient characteristics were collected. Antibiotic duration was classified as <24 hours (short), 24-72 hours (intermediate) or >72 hours (long). Infectious complication data were collected including surgical site infection (SSI), urinary tract infection (UTI), organ space infection, pneumonia, sepsis, and clostridium difficile infection up to 30 days after surgery. Univariate and multivariable analyses were performed to compare duration of antibiotic therapy to infectious outcomes. RESULTS: Of the 4363 patients who underwent radical cystectomy, 3250 (74%), 827 (19%) and 286 (6.6%) received short, intermediate, and long duration of peri-operative antibiotics, respectively. Infectious complication occurred in 954 (22%) patients, including 227 (5.2%) SSI, 280 (6.4%) UTI, 268(6.1%) organ space infection, 87 (2%) pneumonia, and 378 (8.7%) sepsis. Clostridium difficile infection occurred in 89 (2%) patients. On multivariable analysis, there was no significant difference in overall infectious complication rates with long-duration antibiotics. However, intermediate duration of antibiotics in open surgery was associated with a decreased risk of SSI (OR 0.58; 95%CI 0.37-0.91) compared to those treated with short-term antibiotics. CONCLUSION: Despite guideline recommendations, 26% of patients in this database received >24 hours of peri-operative antibiotics without decreased risk of overall infectious complication. An intermediate course of antibiotics decreased risk of SSI in open surgery compared to the guideline recommend <24-hour course. Greater education regarding antibiotic stewardship and further studies investigating infectious complications are warranted.

The Boot Camp Model in Urology: Preparing PGY1 Urology Interns for Practice.

PURPOSE OF REVIEW: The purpose of this review is to highlight literature regarding resident boot camps published across surgical specialties with a focus on urology. Herein, we discuss different boot camp iterations, their results, and the integration of simulation into their curriculum. We review program elements such as curriculum, course length, and efficacy as well as areas for continued investigation. RECENT FINDINGS: The field of urology has grown in both the breadth of knowledge and the complexity of procedures. With urology now being an integrated surgical subspecialty, interns often start on the urology service despite limited experience navigating this unique specialty. The boot camp model is one method by which interns and junior residents participate in consolidated training programs to best prepare them for a patient-facing role and the day-to-day demands of residency. Urology programs, both in the USA and abroad, have begun integrating boot camps into their training programs with positive results. Urology boot camps can be a valuable part of training programs for interns to quickly establish medical knowledge, skills, and efficiency. Boot camps should be easily accessible, have sufficient support from institutions, and provide effective training through various methods such as didactics and simulation.

Chromophobe Renal Cell Carcinoma with Sarcomatoid Differentiation.

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

A Restaging Transurethral Resection of Bladder Tumor Is Always Necessary For High-grade T1 Non-muscle-invasive Bladder Cancer.

Patients with high-grade T1 non-muscle-invasive bladder cancer (NMIBC) have a high risk of recurrence and upstaging. Restaging transurethral resection of bladder tumor allows better staging so that patients can proceed to the appropriate treatment in a timely manner. This should be done in all patients with high-grade T1 NMIBC.

Annual trends of cystectomy complications: A contemporary analysis of the NSQIP database.

INTRODUCTION: Despite significant morbidity, radical cystectomy (RC) is standard of care for muscle invasive bladder cancer, certain high-risk nonmuscle invasive tumors and after failure of intravesical or trimodal therapy. Modern efforts have hastened the recovery after this surgery without impact on overall complication rates. Our primary aim was to examine changes in complication rates of RC over time. METHODS: The National Surgical Quality Improvement Program database included 11,351 RC from 2006 to 2018 for nondisseminated bladder cancer. Baseline characteristics and complication rates were studied across time periods: 2006 to 2011, 2012 to 2014, and 2015 to 2018. Thirty-day complications, readmissions, and mortality were identified. RESULTS: Overall complication rates decreased over time (56.5%, 57.4%, 50.6%, P < 0.01). Infectious complications were stable, including UTIs (10.1%, 8.8%, 8.3% respectively, P = 0.11) and sepsis (10.4%, 8.8%, 8.7% respectively, P = 0.20). On multivariable analysis, ASA≥3 (OR 1.399, 95% CI 1.279-1.530) was associated with increased complications, while procedures in 2015 to 2018 (OR 0.825, 95% CI 0.722-0.942), laparoscopic/robotic approach (OR 0.555, 95%CI 0.494-0.622), and ileal conduit (OR 0.796, 95% CI 0.719-0.882) were associated with decreased complication rates. Other outcomes of interest included mean length of stay (LOS), which decreased over time (10.5, 9.8, 8.6 days, respectively, P < 0.01) and readmission (20.0%, 21.3%, 21.0%, respectively, P = 0.84) and mortality rates were stable (2.7%, 1.7%, 2.0%, respectively, P = 0.13). CONCLUSION: Decreased early complications and LOS after RC over time may reflect beneficial effects of recent advances in bladder cancer treatment such as enhanced recovery after surgery protocols and minimally invasive techniques. Further opportunities to improve long term outcomes, readmissions and infection rates are needed.

Examining the Role of Microbiota-Centered Interventions in Cancer Therapeutics: Applications for Urothelial Carcinoma.

Modern advances in genomic and molecular technologies have sparked substantial research on the human intestinal microbiome over the past decade. A deeper understanding of the microbiome has illuminated that dysbiosis, or a disruption in the microbiome, is associated with inflammatory disease states and carcinogenesis. Novel therapies that target the microbiome and restore healthy flora may have value in dampening the immunopathologic state induced by dysbiosis. A narrative review of the literature on the use of microbiota-centered interventions (MCIs) was conducted. Several randomized clinical trials show that MCIs can augment response to immune checkpoint inhibitor (ICI) therapy in patients with metastatic cancer. Clinical trials have also demonstrated that modulation of the intestinal microbiome can enhance recovery and reduce infectious complications in the surgical management of colorectal adenocarcinoma. Overall, these major discoveries suggest future clinical applications of MCIs for a wide range of immune-mediated conditions. These results may also translate to improved patient outcomes in systemic immunotherapy for urothelial carcinoma as well as in patients recovering from radical cystectomy (RC), which is complicated by high infection rates. Further research is needed to evaluate the optimal bacterial composition of microbiota-centered therapies and the specific cellular changes that lead to improved tumor antigen recognition after microbiota-centered therapies.

Adjuvant Therapy for Renal Cell Carcinoma: End Points, Outcomes, and Risk Assessments.

PURPOSE: Targeted tyrosine kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs) revolutionized the treatment of metastatic renal cell carcinoma (RCC). Efforts to translate these therapies into the adjuvant setting for local and locoregional RCC have been pursued over the past decade. We sought to provide an updated review of the literature regarding adjuvant therapy in RCC, as well as an analysis of patient characteristics that may portend the most favorable responses. MATERIALS AND METHODS: Using PubMed, Google Scholar, and Wiley Online Library, we reviewed articles between 2000 and 2022. Search terms included "tyrosine kinase inhibitors," "adjuvant," "immunotherapy," and "renal cell carcinoma." The articles included were original and published in English. Information on clinical trials was collected from ClinicalTrials.gov, accessed in June 2022. RESULTS: Landmark trials investigating adjuvant vascular endothelial growth factor (VEGF) inhibitors produced conflicting results, with only a single trial of sunitinib (S-TRAC) resulting in US Food and Drug Administration-approval on the basis of a slightly prolonged progression-free survival (PFS). Subsequent meta-analyses failed to show a benefit for adjuvant VEGF inhibitors. Several trials evaluating ICIs are currently ongoing, with pembrolizumab (KEYNOTE-564) earning US Food and Drug Administration-approval for a prolonged PFS, although overall survival data are not yet mature. Preliminary results from other adjuvant ICI trials have been conflicting. CONCLUSION: There remains a lack of clear benefit for the use of adjuvant VEGF inhibitors in local and locoregional RCC. Adjuvant ICI investigations are ongoing, with promising results from KEYNOTE-564. It remains to be seen if PFS is an adequate surrogate end point for overall survival. Selection of patients at greatest risk for recurrence, and identification of those at greatest risk of rare but serious adverse events, may improve outcomes.

Pharmacologic Therapies for Non-Muscle Invasive Bladder Cancer: Current and Future Treatments.

Bladder cancer is the sixth most common malignancy in the United States and 70% of cases are non-muscle invasive at the time of diagnosis. Effective treatment is crucial to prevent progression, which occurs in about 30% of patients. The American Urological Association (AUA) guidelines recommend treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacille Calmette-Guerin (BCG) and chemotherapy. However, ongoing shortages and high rates of BCG unresponsiveness creates a major need for novel therapies. In this narrative review, we discuss the evolving landscape of therapeutic options for NMIBC. Pembrolizumab, an anti-programmed cell death (PD)-1 antibody, was the first systemic therapy to be FDA-approved for BCG-unresponsive, high-risk disease. Promising new agents under investigation include various other checkpoint inhibitors and adenovirus-based therapies including CG0070 and nadofaragene firadenovec (rAd-IFNa/Syn3). Finally, new mechanisms of drug delivery are under investigation, including delivery with the GemRIS (TAR-200) device and delivery of intravesical chemotherapy at higher temperatures. With the promise of novel therapies on the horizon, we can expect the role of urologists in the management of NMIBC to evolve and expand.

Single-Port Robotic Radical Prostatectomy: Short-Term Outcomes and Learning Curve.

Introduction and Objective: In 2018, the U.S. Food and Drug Administration approved the da Vinci single-port (SP) system, in which four instruments are still utilized, but enter through a single-site access trocar. Herein, we report the largest case series for SP robot-assisted radical prostatectomy (RARP) to date. Our primary aim is to analyze the perioperative and short-term outcomes of this procedure. Our secondary aim is an assessment of the learning curve with this new platform. Methods: A total of 157 patients underwent SP RARP by two surgeons who have completed >3000 multiport robotic surgeries collectively. Institutional Review Board-approved prospectively collected data were used. Basic demographic preoperative variables and perioperative outcomes were analyzed. Results: Median patient age and prostate-specific antigen was 63 years and 6.3 ng/mL before treatment (interquartile range [IQR] 4.7-8.2 ng/mL). Average prostate weight was 47 g. The median operating time was 195 minutes (IQR 165-221.25 minutes) with a median estimated blood loss of 100 mL (IQR 100-200 mL). Surgeon 1's operating time stabilized around case #56, and Surgeon 2 around case #26. Surgeon 2 used the transperitoneal approach for the first 7 cases. There were no intraoperative complications. There were six total postoperative complications (3.8%) and four (2.5%) were Clavien-Dindo scale ≥IIIa. One hundred ten patients went home same day, 45 stayed 1 night at the hospital, with only 2 patients requiring stay in the hospital for more than 1 night (70%, 29%, and 1% respectively). With the median follow-up period of 9 months, rates of biochemical recurrence, pad-free, and potency preservation were 8.3%, 82.5%, and 64.4%, respectively. Conclusions: This case series confirms the safety and efficacy of SP RARP with acceptable short-term outcomes. There is a significant learning curve for this new modality. Shorter hospital stay appears to be an early benefit of the SP platform.

New Paradigms for Cytoreductive Nephrectomy.

The role of CN in the treatment of metastatic renal cell carcinoma (mRCC) has been studied over the course of the past few decades. With the advent of immuno-oncologic (IO) agents, there has been a paradigm shift in the treatment of RCC. Within this new era of cancer care, the role of CN is unclear. There are several studies currently underway that aim to assess the role of CN in combination with these therapies. We reviewed articles examining CN, both historically and in the modern immunotherapy era. While immune-oncologic agents are relatively new and large clinical trials have yet to be completed, data thus far is promising that CN may provide clinical benefit. Multiple ongoing trials may clarify the role of CN in this new era of cancer care.

Comparison of perioperative complications for extended vs standard pelvic lymph node dissection in patients undergoing radical prostatectomy for prostate cancer: a meta-analysis.

INTRODUCTION: Pelvic lymph node dissection (PLND) is widely performed for staging in men undergoing radical prostatectomy (RP) for prostate cancer. Our goal was to synthesize all available evidence and data to evaluate perioperative complications for two templates of PLND, standard (sPLND) vs extended (ePLND), at the time of RP in patients with prostate cancer. METHODS: A meta-analysis was performed on relevant literature about complications during PLND. Pubmed, Scopus, WebofScience, and Cochrane Library were systematically searched through July 2021. Meta-analysis was conducted with both fixed-effects and random-effects models to estimate risk ratios (RRs) between treatments. A subgroup analysis was also conducted based on surgery type - open vs robotic. RESULTS: 13 (1 randomized clinical trial and 12 observational studies) studies published between 1997 and 2019 with a total of 7,036 patients were analyzed. Pooled data showed complications in a random-effects model was lower in the sPLND group than the ePLND group (RR, 0.62; 95% CI 0.40-0.97). In a subgroup analysis, neither the open surgery subgroup nor the robotic surgery subgroup showed significant differences in complication rate between sPLND and ePLND. CONCLUSION: ePLND is associated with a significantly greater risk of perioperative complication compared to sPLND, but not when comparing these templates performed via a robotic approach. Additional studies comparing the complication rates of sPLND and ePLND when utilizing a robotic approach should be conducted.

Massive Malignant Epithelioid Angiomyolipoma of the Kidney.

Renal angiomyolipomas (AMLs) are a subset of perivascular epithelioid cell neoplasms (PEComas) that are associated with tuberous sclerosis complex (TSC). Epithelioid angiomyolipomas (EAMLs) are a rare variant of AML with more aggressive propensities. EAMLs with malignant potential can be difficult to distinguish from relatively benign AMLs and other renal tumors. Although there are no established criteria for predicting EAML malignancy, there are proposed histologic parameters that are associated with higher tumor risk. EAML can be treated with surgical resection as well as mTOR inhibitors. Here, we present a unique case of a patient with a 36-cm renal EAML metastatic to the lungs that was treated with complete surgical resection of the primary lesion and mTOR inhibition.

The role of stress in the mosaic of autoimmunity: An overlooked association.

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (Th2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (Th1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.

Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association.

Recurrent pregnancy loss (RPL) affects close to 1% of couples; however, the etiology is known in only about 50% of the cases. Recent studies show that autoimmune dysregulation is a probable cause of RPL, which in some cases may be overlooked. In order for a pregnancy to proceed to term, early modulation of immunologic response is required to induce tolerance to the semi-allogenic fetus. Certain subsets of both the innate and adaptive immune responses play a role in the induction of fetomaternal tolerance. A relatively predominant T-cell helper (Th) 2 and T regulatory (Treg) cell population seem to favor a better pregnancy outcome, whereas Th1 and Th17 cell populations appear to have an opposite effect. Lately, the role of vitamin D in the modulation of immune response was established. Vitamin D has been shown to promote a more favorable environment for pregnancy through various mechanisms, such as enhancement of the shift toward Th2 cells and regulation of immune cell differentiation and cytokine secretion. Therefore, it seems that vitamin D deficiency sways the balance toward a worse outcome and may play a part in recurrent pregnancy loss. This review sheds light on the immunologic changes, which occur in early pregnancy and the regulatory role vitamin D has in the maintenance of this delicate balance.