Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.

Adverse pathologic characteristics in the small renal mass: implications for active surveillance.

INTRODUCTION: Evidence has demonstrated that tumor size is related to adverse oncologic outcomes in small renal tumors (≤ 4 cm). We evaluated the association of adverse pathologic features (APF) with tumor size and survival in patients with a small renal mass (SRM). MATERIALS AND METHODS: We retrospectively reviewed the pathologic characteristics of 380 surgically resected SRMs from a single institution. APFs included lymphovascular invasion, coagulative necrosis, sarcomatoid/rhabdoid features, papillary type II histology, and perinephric fat/renal sinus invasion. The number and type of APFs were compared with tumor size. Survival analysis was performed using the Kaplan-Meier method. RESULTS: There were 244 (64.2%) males and 136 (35.8%) females. The median age was 61 years, and median tumor size was 2.7 cm. The median follow up time was 65 months. A significant association was found between tumor size and presence of APFs (p = 0.018). At least 1 APF could be found in 22%, 32%, 36%, and 49% of tumors ≤ 1 cm, 1 cm-2 cm, 2 cm-3 cm, and 3 cm-4 cm, respectively. There were no differences in overall survival or recurrence free survival when compared by tumor size at diagnosis (p = 0.22 and 0.15 respectively). Compared to patients with ≤ 1 APFs, disease specific survival was worse for patients with ≥ 2 APFs (p < 0.002). CONCLUSION: Our data support that aggressive tumor biology in a SRM is associated with greater size. In patients with a SRM, the decision to pursue active surveillance and the trigger for intervention should take tumor size and APFs into consideration as this may have future oncologic implications.

Robotic-assisted laparoscopic versus open salvage radical prostatectomy following radiotherapy.

INTRODUCTION: To describe immediate perioperative outcomes of robot-assisted laparoscopic salvage radical prostatectomy for recurrent cancer following radiation therapy, and compare outcomes to a contemporary open surgical cohort. MATERIALS AND METHODS: A total of 39 patients underwent salvage radical prostatectomy with pelvic lymphadenectomy (20 robotic, 19 open) for local recurrence following radiation therapy at a single institution between 2007 and 2011. Intraoperative parameters, postoperative complications, and oncological outcomes, were recorded. Wilcoxon rank-sum test and Fisher's exact test were used for comparison of continuous and categorical variables respectively. Mean values of numeric variables are reported with standard deviation. RESULTS: The cohorts were similar with respect to age, ethnicity, and American Society of Anesthesiologists Score classification. Estimated blood loss was lower in the robotic group versus the open group (381.3 mL versus 865.0 mL, p = 0.001). There was no difference in the rate of intraoperative complications, postoperative Clavien = 3 complications (30% versus 15.7%), anastomotic leak (40% versus 42.1%), or wound infection (0% versus 15.7%) in the robotic and open groups. Mean node yield (10.4 versus 11.8), positive surgical margins (15.0% versus 15.7%), and undetectable prostate-specific antigen rate (78% versus 60%) were also similar between the robotic and open groups. CONCLUSIONS: Robotic salvage prostatectomy appears to have no significant difference to the open approach with respect to safety and surgical quality as measured by complications, node yield and surgical margins in this retrospective single-institution series.

Doubling of Decipher Biopsy Genomic Score Is Related to Disease Reclassification on Subsequent Surveillance Biopsy but Not Adverse Features on Radical Prostatectomy.

The utility of serial Decipher biopsy scores in a true active surveillance population is still unknown. In a man on active surveillance for low-risk prostate cancer, a doubling of the Decipher biopsy score within genomic low-risk category from first to the second biopsy related to biopsy reclassification to Gleason grade group 4 on the third biopsy. However, the final pathology at radical prostatectomy showed Gleason grade group 2 with an organ-confined disease. This case suggests that the genomic risk category of Decipher biopsy scores during active surveillance may be more informative than either the interval genomic score change or the biopsy Gleason grade group.

Comparison of long-term outcomes in a 10-year experience of robotic cystectomy vs. open cystectomy.

To compare the outcomes of robotic-assisted (RARC) vs. open radical cystectomy (ORC) at a single academic institution. We retrospectively identified patients undergoing radical cystectomy for urothelial carcinoma of the bladder at our institution from 2007 to 2017. Data collected included age, sex, Body Mass Index (BMI), Charlson Age-Adjusted Comorbidity Index (CCI), final pathologic stage, surgical margins, lymph-node yield, estimated blood loss (EBL), 90-day complication rate, and length of stay (LOS). We evaluated overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox proportional hazard models were used to adjust for covariates. We identified 232 patients (73 RARC, 159 ORC) who underwent radical cystectomy. Patients who underwent RARC were older (71.8 vs. 67.5, p < 0.05) and had higher CCI scores (6.2 vs. 5.3, p < 0.05). In comparing perioperative outcomes, RARC patients had lower EBL (500 vs. 850, p < 0.01), lower blood transfusion rate (p < 0.01), and lower lymph-node yield (12 vs. 20, p < 0.01), and higher ICU admission rate (29% vs. 16% p < 0.01). There was no difference in BMI (p = 0.93), sex (p = 0.28), final pathological stage (p = 0.35), positive surgical margins (p = 0.47), complications (p = 0.58), or LOS (p = 0.34). Kaplan-Meier analysis showed no difference in OS (p = 0.26) or RFS (p = 0.86). There was no difference in restricted mean survival time for OS (53 vs. 56 months, p = 0.81) or for RFS (65 vs. 64 months, p = 0.90). Cox multivariate regression models showed that surgical approach does not have a significant impact on OS (p = 0.46) or RFS (p = 0.35). Our study indicates that in our 10-year experience, patients undergoing there was no difference between RARC and ORC patients with respect to OS and RFS despite being older and having more comorbidities. Our work supports the importance of patient selection to optimize outcomes.

Effect of Diaphragmatic Breathing on Procedural Anxiety During Transrectal Prostate Biopsy.

OBJECTIVE: To improve the tolerability of transrectal ultrasound guided prostate biopsy through use of diaphragmatic breathing. METHODS: Forty-seven patients, aged 52-79 years, who were scheduled for a transrectal ultrasound guided prostate biopsy with or without MRI guidance, were recruited at a single Veterans Affairs medical center for the diagnosis or evaluation of prostate cancer. Patients either met with a health psychologist for a 1-time, diaphragmatic breathing intervention immediately prior to their biopsy, or received usual care. All biopsies were performed using local anesthetic without sedation or anxiolytic therapy. The primary outcome was the difference in self-reported procedural situational anxiety as measured with the State Trait Anxiety Inventory, assessed both pre- and post-transrectal ultrasound guided prostate biopsy. We also examined secondary outcomes including physiological parameters (heart rate and blood pressure). RESULTS: There were no significant differences in preprocedural anxiety or physiological parameters between patients who received the intervention and those who received usual care. Patients who received the intervention had a significantly larger decrease in situational anxiety from pre- to postprocedure (M = 14.15, SD = 6.64) compared with those who received usual care (M = 3.45, SD = 9.97); t (38) = -4.0, P <.000; d = 1.26. Patients who received the intervention had a significantly larger decrease in heart rate (bpm) from pre- to postprocedure (M = 10.63, SD = 12.21) compared with those who received usual care (M = 0.07, SD = 9.25); t (31) = 2.75 P = 0.010; d = 0.97. CONCLUSION: A guided diaphragmatic breathing intervention reduced procedural anxiety during prostate biopsy and improved patient experience.

Learning Non-rigid Deformations for Robust, Constrained Point-based Registration in Image-Guided MR-TRUS Prostate Intervention.

Accurate and robust non-rigid registration of pre-procedure magnetic resonance (MR) imaging to intra-procedure trans-rectal ultrasound (TRUS) is critical for image-guided biopsies of prostate cancer. Prostate cancer is one of the most prevalent forms of cancer and the second leading cause of cancer-related death in men in the United States. TRUS-guided biopsy is the current clinical standard for prostate cancer diagnosis and assessment. State-of-the-art, clinical MR-TRUS image fusion relies upon semi-automated segmentations of the prostate in both the MR and the TRUS images to perform non-rigid surface-based registration of the gland. Segmentation of the prostate in TRUS imaging is itself a challenging task and prone to high variability. These segmentation errors can lead to poor registration and subsequently poor localization of biopsy targets, which may result in false-negative cancer detection. In this paper, we present a non-rigid surface registration approach to MR-TRUS fusion based on a statistical deformation model (SDM) of intra-procedural deformations derived from clinical training data. Synthetic validation experiments quantifying registration volume of interest overlaps of the PI-RADS parcellation standard and tests using clinical landmark data demonstrate that our use of an SDM for registration, with median target registration error of 2.98 mm, is significantly more accurate than the current clinical method. Furthermore, we show that the low-dimensional SDM registration results are robust to segmentation errors that are not uncommon in clinical TRUS data.

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in patients with a solitary PI-RADS v2-scored lesion.

PURPOSE: To evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: A total of 176 patients underwent MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location. RESULTS: Fusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone. CONCLUSION: The PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ.

Negative Multiparametric Magnetic Resonance Imaging of the Prostate Predicts Absence of Clinically Significant Prostate Cancer on 12-Core Template Prostate Biopsy.

OBJECTIVE: To determine the negative predictive value of multiparametric magnetic resonance imaging (mpMRI), we evaluated the frequency of prostate cancer detection by 12-core template mapping biopsy in men whose mpMRI showed no suspicious regions. METHODS: Six hundred seventy patients underwent mpMRI followed by transrectal ultrasound (TRUS)-guided systematic prostate biopsy from December 2012 to June 2016. Of this cohort, 100 patients had a negative mpMRI. mpMRI imaging sequences included T2-weighted and diffusion-weighted imaging, and dynamic contrast enhancement sequences. RESULTS: The mean age, prostate-specific antigen, and prostate volume of the 100 men included were 64.3 years, 7.2 ng/mL, and 71 mL, respectively. Overall cancer detection was 27% (27 of 100). Prostate cancer was detected in 26.3% (10 of 38) of patients who were biopsy-naïve, 12.1% (4 of 33) of patients who had a prior negative biopsy, and in 44.8% (13 of 29) of patients previously on active surveillance; Gleason grade ≥7 was detected in 3% of patients overall (3 of 100). The negative predictive value of a negative mpMRI was 73% for all prostate cancer and 97% for Gleason ≥7 prostate cancer. CONCLUSION: There is an approximately 3% chance of detecting clinically significant prostate cancer with systematic TRUS-guided biopsy in patients with no suspicious findings on mpMRI. This information should help guide recommendations to patients about undergoing systematic TRUS-guided biopsy when mpMRI is negative.

Age and Prostate-Specific Antigen Level Prior to Diagnosis Predict Risk of Death from Prostate Cancer.

A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50-89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50-59 years, through 80-89 years) and PSA range at diagnosis (10 ranges) using Kaplan-Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7-10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50-59 years to 51% for age 80-89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study.

Diagnostic laparoscopy after anterior abdominal stab wounds: worth another look?

BACKGROUND: The National Institute of Medicine's report Hospital-Based Emergency Care: At the Breaking Point highlighted the critical issue of emergency department overcrowding. At our institution, patients with anterior abdominal stab wounds (AASW) have been managed with a protocol that uses diagnostic laparoscopy (DL) after positive result on local wound exploration. Patients with negative DL result are eligible for discharge directly from the recovery room. The purpose of this study was to evaluate the use of DL for AASWs in light of the recommendations that suggested serial abdominal examination (SAE) is preferred to determine the need for laparotomy. METHODS: Patients admitted to a Level 1 trauma center from January 2010 through August 2012 with AASWs were included (contemporary period to Western Trauma Association study). Information regarding baseline characteristics, diagnostic workup, injury management, and outcomes were retrospectively reviewed and compared with the SAE AASW algorithm. RESULTS: A total of 158 patients with AASWs were evaluated using our institutional algorithm. Thirty-eight patients (24%) went directly to the operating room for peritonitis, shock, or evisceration; 120 underwent local wound exploration; 99 had positive result (82%). Twenty-eight patients had immediate laparotomy owing to worsening clinical examination findings. Seventy had DL, and 19 of these patients were discharged home from the recovery room, with a mean length of stay of 6.4 hours. When comparing patients managed using the DL algorithm to those managed using the SAE-based algorithm, the nontherapeutic laparotomy rate was lower, although not statistically significant. However, the DL algorithm produced a significantly higher percentage of patients discharged directly home following local wound exploration. CONCLUSION: With some trauma centers suffering from emergency department overcrowding and constrained resources, DL may offer an alternative to SAE to efficiently use available resources. Both SAE and DL are safe and offer similar therapeutic laparotomy rates. The method used to evaluate patients after AASW should be tailored to institutional needs and resources. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Fat embolism syndrome in an adolescent before surgical treatment of an isolated closed tibial shaft fracture.

Fat embolism syndrome (FES) occurs most commonly in adults with high-energy trauma, especially fractures of the long-bones and pelvis. Because of unique age-related physiologic differences in the immature skeleton, as well as differences in fracture management in pediatric patients, FES is rare in children. To our knowledge, this is the first case report of FES occurring before surgical fixation of a closed tibial shaft fracture in an adolescent. A 16-year-old, 109 kg, Caucasian adolescent boy developed FES after closed diaphyseal fractures of the distal tibia and fibula, showing signs of respiratory distress and mental status changes. The FES resolved with supportive respiratory care and intramedullary nailing of the fracture was done without further respiratory compromise. FES is uncommon in children and adolescents. A high index of suspicion is required to make the diagnosis promptly and institute appropriate treatment. Intramedullary nailing of a long-bone fracture can be done safely and successfully after resolution of the FES.