Extrarenal, Soft Tissue Malignant Rhabdoid Tumor Arising in the Mons Pubis.

Extrarenal, extracranial malignant rhabdoid tumors (MRT) are uncommon malignancies with poor prognoses that may be diagnostically challenging. Reports of soft tissue MRTs in children are rare. For this reason, there are no standard treatment protocols. Historically, an aggressive multimodal approach has been taken. Here, we present a case of metastatic superficial pelvic MRT in a 16-year-old girl who remains disease-free after aggressive multi-modal therapy.

Aggressive Multimodality Therapy for a Urachal Rhabdomyosarcoma.

Urachal rhabdomyosarcoma is a rare entity with a remarkably poor prognosis. Here we report on a 2-year-old male who presented with abdominal pain, fatigue, and urinary frequency. Imaging and subsequent surgical pathology confirmed urachal primary embryonal rhabdomyosarcoma. Our patient underwent upfront surgical resection with adjuvant chemoradiation per Children's Oncology Group protocol D9803. He is doing well 15 months after diagnosis.

Impact of an Acute Care Urology Service on Timelines and Quality of Care in the Management of Nephrolithiasis.

Background: The acute care surgery model has led to improved outcomes for emergent surgical conditions, but similar models of care have not been implemented in urology. Our department implemented an acute care urology (ACU) service in 2015, and the service evolved in 2018. We aimed to evaluate the impact of the ACU model on the management of nephrolithiasis. Materials and Methods: We conducted a retrospective review of all patients with urology consults in the emergency department for nephrolithiasis, who required surgical intervention from 2013 to 2019. Patients were divided into three cohorts based on date of consultation: Pre-ACU (2013-2014), Phase 1 (2015-2017), and Phase 2 (2018-2019). Results: We identified 733 patients with nephrolithiasis requiring intervention (162 pre-ACU, 334 Phase 1, and 237 Phase 2). Before ACU implementation, median time from consult to definitive intervention was 36 days. After ACU implementation, median time to intervention decreased to 22 days in Phase 1 (p < 0.001) and 15 days in Phase 2 (p < 0.001). On multivariable Cox regression, the hazard of definitive intervention improved in Phase 1 (hazard ratio [HR] 1.90, p < 0.001) and in Phase 2 (HR 1.80, p < 0.001). Rates of primary definitive intervention without initial decompression and loss to follow-up were also significantly improved, compared to the pre-ACU cohort. Conclusions: Implementation of a structured ACU service was associated with improved time to treatment for patients with acute nephrolithiasis, as well as increased primary definitive intervention and improved follow-up care. This model of care has potential to improve patient outcomes for nephrolithiasis and other acute urological conditions.

Adaptive Immune Resistance to Intravesical BCG in Non-Muscle Invasive Bladder Cancer: Implications for Prospective BCG-Unresponsive Trials.

PURPOSE: To characterize immune cell expression among patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guerin (BCG). EXPERIMENTAL DESIGN: Patients with NMIBC treated with intravesical BCG (2008-2015) were identified, and a tissue microarray was constructed using paired pre- and post-BCG bladder samples. Among patients undergoing BCG, cystoscopic evaluation began 3 months after initiating BCG treatment to determine therapeutic response. IHC was performed for CD8, CD4, FoxP3, PD-L1 (SP-142 and 22C3), and PD-1. A full slide review of PD-L1+ staining tumors was performed to characterize PD-L1 and CD8 colocalization. RNA-seq was performed on cored tumors from available specimens. We compared immune cell populations between BCG responders and nonresponders, and between pretreatment and postreatment tumor samples. Baseline PD-L1 staining in the BCG naïve population was then validated in a separate cohort. RESULTS: The final cohort contained 63 pretreatment NMIBC cases, including 31 BCG responders and 32 BCG nonresponders. No differences in CD4, CD8, or FoxP3 expression were identified between responders and nonresponders. Baseline PD-L1 expression (22C3 and SP-142) was observed in 25% to 28% of nonresponders and 0% to 4% of responders (P < 0.01). PD-L1+ cells in BCG nonresponders colocalized with CD8+ T cells. In addition, BCG therapy did not increase PD-L1 gene expression (RNA-seq) or protein levels (IHC). The number of pretreatment CD4+ T cells was very low among PD-L1+ nonresponders (12%) and high among PD-L1- nonresponders (50%, P < 0.01). In a separate cohort of 57 patients with NMIBC undergoing BCG, baseline PD-L1 (22C3) staining was similar (26%). CONCLUSIONS: One mechanism of BCG failure may be adaptive immune resistance. Baseline tumor PD-L1 expression predicts an unfavorable response to BCG and if validated, could be used to guide therapeutic decisions.

Use of the Quick Sequential Organ Failure Assessment Score for Prediction of Intensive Care Unit Admission Due to Septic Shock after Percutaneous Nephrolithotomy: A Multicenter Study.

PURPOSE: Recent studies have demonstrated that quick sequential organ failure assessment criteria may be more accurate than systemic inflammatory response syndrome criteria to predict postoperative sepsis. In this study we evaluated the ability of these 2 criteria to predict septic shock after percutaneous nephrolithotomy. MATERIALS AND METHODS: We performed a retrospective multicenter study in 320 patients who underwent percutaneous nephrolithotomy at a total of 8 institutions. The criteria for quick sequential organ failure assessment and systemic inflammatory response syndrome were collected 24 hours postoperatively. The study primary outcome was postoperative septic shock. Secondary outcomes included 30 and 90-day emergency department visits, and the hospital readmission rate. RESULTS: Three of the 320 patients (0.9%) met the criteria for postoperative septic shock. These 3 patients had positive criteria for quick sequential organ failure assessment and systemic inflammatory response syndrome. Of the entire cohort 23 patients (7%) met quick sequential organ failure assessment criteria and 103 (32%) met systemic inflammatory response syndrome criteria. Specificity for postoperative sepsis was significantly higher for quick sequential organ failure assessment than for systemic inflammatory response syndrome (93.3% vs 68.4%, McNemar test p <0.001). The positive predictive value was 13% for quick sequential organ failure assessment criteria and 2.9% for systemic inflammatory response syndrome criteria. On multivariate logistic regression systemic inflammatory response syndrome criteria significantly predicted an increased probability of the patient receiving a transfusion (ß = 1.234, p <0.001). Positive quick sequential organ failure assessment criteria significantly predicted an increased probability of an emergency department visit within 30 days (ß = 1.495, p <0.05), operative complications (ß = 1.811, p <0.001) and transfusions (p <0.001). The main limitation of the study is that it was retrospective. CONCLUSIONS: Quick sequential organ failure assessment criteria were superior to systemic inflammatory response syndrome criteria to predict infectious complications after percutaneous nephrolithotomy.

Misinformation on the Internet regarding Ablative Therapies for Prostate Cancer.

OBJECTIVE: To evaluate the quality of web-based information on ablative therapies for prostate cancer. METHODS: The 2 most common search engines (Google and Bing) were queried for the following terms: "prostate cancer" + "HIFU" and "cryotherapy," respectively. The top 50 websites for each were obtained. Websites were characterized and analyzed regarding their accuracy and completeness of information using criteria determined a priori. Academic papers were excluded. RESULTS: Of "HIFU" search results, 17% were advertisements, 13% and 29% were academic and private practice websites, respectively. Erroneous information on oncological efficacy was presented in 15% and 41% of academic and private practice websites, respectively. Criteria for treatment were mentioned in 31% and 66% of academic and private practice websites, respectively. Of "cryotherapy" search results, 18% were advertisements, 15% academic sites, and 11% private practices. Erroneous information was presented in 73% of both academic and private practice websites. Criteria for treatment were mentioned in 27% and 18% of these sites, respectively. Seventy eight percent and 75% of HIFU and cryotherapy sites, respectively, mentioned general side effects. CONCLUSION: There is substantial inaccurate and incomplete information on the Internet regarding ablative treatments for prostate cancer from academic and private practice websites. Selection criteria are uncommonly discussed. More attention to accuracy of information is needed to ensure patients are not misled about the data behind these treatments.

Prospective Evaluation of Unprocessed Core Needle Biopsy DNA and RNA Yield from Lung, Liver, and Kidney Tumors: Implications for Cancer Genomics.

CONTEXT: Targeted needle biopsies are increasingly performed for the genetic characterization of cancer. While the nucleic acid content of core needle biopsies after standard pathology processing (i.e., formalin fixation and paraffin embedding (FFPE)) has been previously reported, little is known about the potential yield for molecular analysis at the time of biopsy sample acquisition. OBJECTIVES: Our objective was to improve the understanding of DNA and RNA yields from commonly used core needle biopsy techniques prior to sample processing. METHODS: We performed 552 ex vivo 18 and 20G core biopsies in the lungs, liver, and kidneys. DNA and RNA were extracted from fresh-frozen core samples and quantified for statistical comparisons based on needle gauge, biopsy site, and tissue type. RESULTS: Median tumor DNA yields from all 18G and 20G samples were 5880 ng and 2710 ng, respectively. Median tumor RNA yields from all 18G and 20G samples were 1100 ng and 230 ng, respectively. A wide range of DNA and RNA quantities (1060-13,390 ng and 370-6280 ng, respectively) were acquired. Median DNA and RNA yields from 18G needles were significantly greater than those from 20G needles across all organs (p < 0.001). CONCLUSIONS: Core needle biopsy techniques for cancer diagnostics yield a broad range of DNA and RNA for molecular pathology, though quantities are greater than what has been reported for FFPE processed material. Since non-formalin-fixed DNA is advantageous for molecular studies, workflows that optimize core needle biopsy yield for molecular characterization should be explored.

The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling.

Primary clear cell renal cell carcinoma (ccRCC) genetic heterogeneity may lead to an underestimation of the mutational burden detected from a single site evaluation. We sought to characterize the extent of clonal branching involving key tumor suppressor mutations in primary ccRCC and determine if genetic heterogeneity could limit the mutation profiling from a single region assessment. Ex vivo core needle biopsies were obtained from three to five different regions of resected renal tumors at a single institution from 2012 to 2013. DNA was extracted and targeted sequencing was performed on five genes associated with ccRCC (von-Hippel Lindau [VHL], PBRM1, SETD2, BAP1, and KDM5C). We constructed phylogenetic trees by inferring clonal evolution based on the mutations present within each core and estimated the predictive power of detecting a mutation for each successive tumor region sampled. We obtained 47 ex vivo biopsy cores from 14 primary ccRCC's (median tumor size 4.5 cm, IQR 4.0-5.9 cm). Branching patterns of various complexities were observed in tumors with three or more mutations. A VHL mutation was detected in nine tumors (64%), each time being present ubiquitously throughout the tumor. Other genes had various degrees of regional mutational variation. Based on the mutations' prevalence we estimated that three different tumor regions should be sampled to detect mutations in PBRM1, SETD2, BAP1, and/or KDM5C with 90% certainty. The mutational burden of renal tumors varies by region sampled. Single site assessment of key tumor suppressor mutations in primary ccRCC may not adequately capture the genetic predictors of tumor behavior.

Impact of recurrent copy number alterations and cancer gene mutations on the predictive accuracy of prognostic models in clear cell renal cell carcinoma.

PURPOSE: Several recently reported recurrent genomic alterations in clear cell renal cell carcinoma are linked to pathological and clinical outcomes. We determined whether any recurrent cancer gene mutations or copy number alterations identified in the TCGA (The Cancer Genome Atlas) clear cell renal cell carcinoma data set could add to the predictive accuracy of current prognostic models. MATERIALS AND METHODS: In 413 patients who underwent nephrectomy/partial nephrectomy we investigated whole exome, copy number array analyses and clinical variables. We identified 65 recurrent genomic alterations based on prevalence and combined them into 35 alterations, including 12 cancer gene mutations. Genomic markers were modeled using the elastic net algorithm with preoperative variables (tumor size plus patient age) and in the postoperative setting using the externally validated Mayo Clinic SSIGN (stage, size, grade and necrosis) prognostic scoring system. These models were subjected to internal validation using bootstrap. RESULTS: Median followup in survivors was 45 months. Several markers correlated with adverse cancer specific survival and time to recurrence on univariate analysis. However, most of them lost significance when controlling for tumor size with or without age in the preoperative models or for SSIGN score in the postoperative setting. Adding multiple genomic markers selected by the elastic net algorithm failed to substantially add to the predictive accuracy of any preoperative or postoperative model for cancer specific survival or time to recurrence. CONCLUSIONS: While recurrent copy number alterations and cancer gene mutations are biologically significant, they do not appear to improve the predictive accuracy of existing models of clinical cancer specific survival or time to recurrence for clear cell renal cell carcinoma.