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Improvements in chemistry, molecular biology, genetics, and bioinformatics have allowed broad use of transcriptomic profiling. Understanding the population of ribonucleic acid (RNA) transcripts can provide important clinical information relevant to kidney cancer care. This includes a better understanding of kidney cancer subtype and distinct clusters within these categories. RNA-sequencing (RNA-seq) is typically done on a region within the tumor, which represents thousands to millions of heterogeneous cells and various components of the microenvironment. Computational tools can deconvolute these populations to provide insight into the microenvironment. Specific signatures of hypoxia, proliferation, angiogenesis and immune infiltration can predict response and survival. Prognostic signatures can risk stratify tumors to aid in identification of patients who might derive benefit from adjuvant therapy. As the cost of sequencing continues to decline and improved bioinformatic tools are developed, the barriers to clinical use of transcriptomic data continue to crumble. Here we review the current literature around the use of transcriptomics in kidney cancer diagnosis and management.

To determine which method of radiotherapy proves more effective after prostatectomy: Adjuvant (ART) or early salvage (ESRT), we observed the pathologic and adverse risk factors of patients and their results from both treatments, looking specifically at biochemical-free survival rates, metastasis-free survival rates, and overall survival rates. Peer review articles containing their own data collected between 1986 and 2022 were reviewed. We reviewed 67 peer review articles and included 33 that met criteria. Studies focused on the adverse risk factors and the results of patients either before/after receiving adjuvant or early salvage/salvage radiotherapy were included in the analysis. Patient characteristics had an effect on what treatment a patient would receive; if a patient had more than one adverse risk factor such as a high Gleason score, prostate-specific antigen (PSA) level, T-stage, or positive margins, they would receive immediate radiation after prostatectomy, which would classify as ART. If the patient had no adverse risk factors after surgery, they would be placed in an observation period to follow their PSA and overall health, and only if necessary, undergo ESRT. Of the 33 studies, ART was proven to be only slightly more beneficial when relating to biochemical recurrence-free survival while ART and ESRT results were similar in metastasis-free survival and overall survival. ART and ESRT are overall comparable in their patient outcomes, despite their own unique pros and cons. The use of ESRT reduces overtreatment in men who may not experience biochemical recurrence. However, in those with very high-risk pathologic features, a multi-disciplinary approach should be utilized to best determine which mode of radiation therapy after surgery is recommended.

The incremental morbidity of lymph node dissection (LND) among men undergoing radical prostatectomy remains uncertain. We therefore evaluated the association of LND with perioperative morbidity among men undergoing minimally invasive radical prostatectomy (MIRP). We identified 29,012 men aged 35–89 who underwent MIRP from 2010–2015 in the National Surgical Quality Improvement Program (NSQIP) database, of whom 47% underwent concomitant LND. The associations of LND with 30-day perioperative morbidity and mortality were evaluated using logistic regression, adjusted for patient features. Median age at surgery was 63 (IQR 57, 67) years. There were statistically significant, but clinically insignificant, differences in several baseline characteristics stratified by performance of LND, including older age at surgery (p

INTRODUCTION AND OBJECTIVE:Pelvic lymph node dissection (LND) is an integral component of the surgical treatment of invasive urothelial carcinoma of the bladder. Although an extended surgical templ...

Prostate cancer management changed in recent times given the recommendation against prostate-specific antigen screening, adherence to active surveillance, and "cytoreductive" surgery. We hypothesized that radical prostatectomy (RP) findings changed as well. All consecutive RPs (n=1348) and first time prostate needle biopsies (n=1719) in a period of 9 years were reviewed. The cohort was separated into 3 groups: (1) from May 2006 to April 2009, (2) from May 2009 to April 2012, and (3) from May 2012 to April 2015. The number of RPs decreased 15% from 551 in group 1 to 476 in group 2 and decreased a further 35% to 311 in group 3. Pure Gleason 6 (grade group 1) decreased from 46% in group 1 to 24% in group 2 (P

With the increasing use of minimally invasive technologies for the treatment of benign prostatic enlargement/lower urinary tract symptoms, clinicians must become familiar with the various treatment effects and complications. Here we present a case of treatment defect after transurethral convective radiofrequency-induced water vapor thermal ablation (REZUM) radiographically identified as a prostatic abscess without consideration that the finding may have represented an anticipated treatment defect. This likely led to an unnecessary surgical procedure. This entity should be recognized by urologists and radiologists alike to avoid such interventions in the future.

OBJECTIVE: To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. METHODS: Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluorescent (NIRF) imaging using a Stryker 1588 AIM imaging system. Standard histopathologic evaluation was performed and findings were correlated with white light and ICG-Var3 NIRF imaging. One patient who underwent radical nephrectomy for renal cell carcinoma was used as a negative control. RESULTS: Nineteen lesions were identified on histopathologic evaluation in 10 patients, including 82% high-grade urothelial carcinoma and 18% low-grade urothelial carcinoma. Nineteen (100%) malignant lesions were identified using NIRF imaging, while 15 (78.9%) lesions were identified using conventional white light examination. The sensitivity of ICG-Var3 pHLIP NIRF imaging was 100% compared to 78.9% white light examination. Both modalities are 100% specific. Benign collecting systems and ureters did not show uptake of the pHLIP construct. CONCLUSION: In this feasibility study, the ICG-Var3 pHLIP imaging agent demonstrated superior diagnostic performance compared to conventional white light examination. While additional studies are required for validation and in-vivo translation, pHLIP-based imaging represents a promising tool to improve the evaluation and management of upper tract urothelial carcinoma. UROLOGY 139: 134–140, 2020.

A twenty-eight-year-old female with a history of suprapubic pain and recurrent urinary tract infections presents for urology referral with a kidney, ureter, and bladder radiograph showing a 4.4 cm bladder calculus and 6.5 cm distal left ureteral stone. She underwent effective cystolitholapaxy of the bladder stone. Endourologic attempt (left ureteroscopy) was unsuccessful because of ureteral stone burden. Findings at ureteroscopy revealed a duplicated system on the left with the lower pole moiety joining just proximal to the ureteral orifice. The stone was found to be in the upper pole moiety ureter. An open ureterolithotomy was performed with intraoperative ureteroscopic laser lithotripsy and common sheath ureteral reimplant. Furthermore, a previously placed stent was found to be encrusted at the time of the ureterolithotomy. Effective ureteroscopy and lasering were performed through the ureterotomy up to the renal pelvis of the upper pole ureter.

Gross hematuria is a common urologic problem which often requires surgical intervention. While generally a safe procedure, clot evacuation can have serious complications. Here we describe the case of an 85-year-old male who developed extensive subcutaneous emphysema following a small extraperitoneal bladder perforation during a clot evacuation. While our patient did well with expectant management, subcutaneous emphysema can lead to serious complications and any endourologic procedure should be stopped once crepitus is noted.

The role of lymph node dissection (LND) in the management of renal cell carcinoma has been controversial. Older studies provided initial support to a potential survival benefit in resection of lymph node metastases, and several predictive models were developed to identify patients with lymph node involvement. However, the only randomized trial on the subject did not report a survival benefit to LND in the nonmetastatic setting. Several studies have recently reexplored the therapeutic benefit of LND. In both nonmetastatic and metastatic settings, LND does not appear to be associated with a survival benefit. Moreover, it does not appear that LND confers a survival advantage to patients at increased risk of lymph node metastases, such as those with preoperative radiographic lymphadenopathy or across increasing probability of lymph node disease. Among patients with clinically isolated lymph node metastases, the majority develop disease progression following surgical resection, suggesting a high prevalence of occult systemic disease. Lymph node metastases appear to have prognostic value in both nonmetastatic and metastatic settings. LND may, therefore, have an increasingly important staging role in the management of renal cell carcinoma.

Kidney masses suspicious for malignancy are frequently detected by cross-sectional imaging; however, little is known about the burden of surgical treatment for tumors found to be benign following excision.We queried the National Inpatient Sample to identify records of individuals who received surgical treatment for renal neoplasms between 2004 and 2014. We characterized temporal treatment trends, patient demographics, treatment related complications, and charges.We identified 7,099 (8.5%) and 76,892 (91.5%) patients who were treated for benign and malignant tumors, respectively. Benign masses accounted for 14.8% of partial and 5.5% of radical nephrectomies. The rates of surgery for benign tumors have remained steady (P = 0.058). The frequency of inpatient death was higher in those with malignant disease (0.63% vs. 0.18%, P0.0001). Median length of stay was longer for individuals with malignant renal tumors (4.86 vs. 4.12 days, P0.0001). The total discharge bill adjusting for inflation for benign or malignant renal surgery increased each year (R8.5% of inpatient renal surgical admissions are performed for benign masses. There has been a trend toward decreased operative management for benign renal tumors over time. Surgical management remains a significant economic burden. Efforts to prospectively evaluate modalities for pretreatment identification should be further pursued.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

The American Urological Association (AUA) guidelines recommend partial nephrectomy (PN) as the gold standard for treatment of small renal masses (SRMs). This study examines the change in utilization of partial and radical nephrectomies at teaching and nonteaching institutions from 2003 to 2012.The data sample for this study came from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 2003 to 2012. International Classification of Diseases, Ninth Revision and Clinical Modification codes were used to identify patients undergoing PN and radical nephrectomy for renal masses limited to the renal parenchyma. Teaching hospitals were defined, but not limited to any institution with an American Medical Association-approved residency program. Linear regression, bivariate, multivariate, and odds ratio analysis were used to demonstrate statistical significance.39,685 patients were identified in teaching hospitals, and 22,239 were identified in nonteaching hospitals. Prior to the 2009 AUA guidelines, cumulative rates of PN were 33% vs 20% in teaching vs nonteaching hospitals (p 0.0001) compared with postguideline rates of 48% vs 33% in teaching vs nonteaching hospitals (p 0.0001).During the 10-year study period, the use of PN to treat SRMs has significantly increased in both teaching hospitals and in nonacademic centers; however, these changes are occurring at a slower rate in nonteaching hospitals.

Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation.

e16126Background: Subclassificaiton of papillary RCC (pRCC) into type 1 and type 2 has been recognized as an independent negative prognostic factor. Little investigation has determined the effect o...

Transgenic expression of activated AKT1 in the murine prostate induces prostatic intraepithelial neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN, we show the concomitant induction of p27(Kip1) and senescence. Genetic ablation of p27(Kip1) led to downregulation of senescence markers and progression to cancer. In humans, p27(Kip1) and senescence markers were elevated in PIN not associated with CaP but were decreased or absent, respectively, in cancer-associated PIN and in CaP. Importantly, p27(Kip1) upregulation in mouse and human in situ lesions did not depend upon mTOR or Akt activation but was instead specifically associated with alterations in cell polarity, architecture, and adhesion molecules. These data suggest that a p27(Kip1)-driven checkpoint limits progression of PIN to CaP.

Sarcoma represents a class of tumors arising from mesenchymal tissue. New approaches that target sarcoma-specific molecular alterations hold a promise of more effective therapies. Currently available sarcoma models do not accurately resemble relevant properties of the human disease and very often are inadequate for predicting the efficacy of investigational drugs in preclinical settings. Thus, in order to test novel targeted therapies, it is essential to develop in vivo models of sarcomas. To this end, we have created a panel of well-characterized xenografts of primary human sarcomas that represent a spectrum of histotypes. Specifically, we transplanted intact human sarcomas under the skin of immunodeficient mice. We then compared the morphologic, phenotypic, and genetic characteristics of the tumor tissues before and after implantation in recipient mice. To date, we have implanted into Nu/Nu recipients tumor tissue fragments from 32 gastrointestinal stromal tumors (GIST) 10 dedifferentiated liposarcomas and 6 leiomyosarcomas. Successful tumor growth was detected in 86% cases of GIST, 44% of liposarcomas and 33% of leiomyosarcomas. Upon serial transplantation, 35% of GISTs, 44% of liposarcomas and 33% of leiomyosarcomas have grown beyond passage F3. Histological analysis of the primary tumors and corresponding xenografts revealed that morphology and immunophenotype (c-Kit status for GISTs, MDM2 for liposarcomas, Smooth Muscle Actin for leiomyosarcomas) was retained throughout all passages. Moreover, all major genetic abnormalities present in the primary tumors were retained in the xenografts, as revealed by genome-wide Single Nucleotide Polymorphism (SNP) array analyses. Our results show that this approach can be used to generate animal models that faithfully reproduce characteristics of human intact tumors. These models can be used for in vivo preclinical drug testing, diagnostic and prognostic molecular markers discovery, and for identification of molecular mechanisms of drug resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4197.