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1.
Transl Oncol ; 37: 101763, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37657155

ABSTRACT

Up to 430,000 cases of bladder cancer are diagnosed each year worldwide. A proposed method for non-invasive monitoring has been to utilize a "liquid biopsy." Liquid biopsy has been proposed as a non-invasive method of testing biomarkers in bodily fluids in order to detect and survey cancer. The liquid biopsy could be utilized to obtain information regarding circulating tumor cells, circulating cell-free tumor DNA, circulating cell-free tumor RNA, and more. It is currently being investigated to help guide adjuvant therapy and improve oncological outcomes. We highlight an array of exciting past and ongoing clinical trials regarding ctDNA and adjuvant therapy in regard to urothelial carcinoma which we believe to be amongst the leaders in the field.

2.
NPJ Precis Oncol ; 7(1): 6, 2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36658307

ABSTRACT

Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to the disease, urine, and analyzed urine tumor DNA in 74 localized bladder cancer patients. We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with urine cancer personalized profiling by deep sequencing (uCAPP-Seq) to achieve sensitive MRD detection and predict overall survival. Variant allele frequency, inferred tumor mutational burden, and copy number-derived tumor fraction levels in urine cell-free DNA (cfDNA) significantly predicted pathologic complete response status, far better than plasma ctDNA was able to. A random forest model incorporating these urine cfDNA-derived factors with leave-one-out cross-validation was 87% sensitive for predicting residual disease in reference to gold-standard surgical pathology. Both progression-free survival (HR = 3.00, p = 0.01) and overall survival (HR = 4.81, p = 0.009) were dramatically worse by Kaplan-Meier analysis for patients predicted by the model to have MRD, which was corroborated by Cox regression analysis. Additional survival analyses performed on muscle-invasive, neoadjuvant chemotherapy, and held-out validation subgroups corroborated these findings. In summary, we profiled urine samples from 74 patients with localized bladder cancer and used urine cfDNA multi-omics to detect MRD sensitively and predict survival accurately.

3.
Case Rep Urol ; 2021: 2060572, 2021.
Article in English | MEDLINE | ID: mdl-34603812

ABSTRACT

BACKGROUND: Intraoperative imaging for endourologic procedures is generally limited to single-plane fluoroscopic X-ray. The O-arm™ is a mobile cone-bean CT scanner that may have applications in urologic surgeries. Case Presentation. We present a case of an 85-year-old male with radiation cystitis and recurrent gross hematuria who was identified to have a bladder perforation on cystoscopy during emergent clot evacuation. Single-view fluoroscopic evaluation was inconclusive as to whether an intraperitoneal bladder perforation occurred. A portable cone-beam CT scan was used to acquire a 3-D CT cystogram, which demonstrated intraperitoneal contrast extravasation, confirming the diagnosis of an intraperitoneal bladder perforation. CONCLUSION: We report the first use of a portable cone-beam CT scanner to perform an intraoperative CT cystogram to diagnose an intraperitoneal bladder perforation and guide surgical management.

4.
Case Rep Urol ; 2021: 2687416, 2021.
Article in English | MEDLINE | ID: mdl-33936831

ABSTRACT

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.

5.
J Robot Surg ; 15(5): 773-780, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33226567

ABSTRACT

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.


Subject(s)
Carcinoma, Transitional Cell , Robotic Surgical Procedures , Urinary Bladder Neoplasms , Cystectomy/adverse effects , Humans , Postoperative Complications/epidemiology , Retrospective Studies , Robotic Surgical Procedures/methods , Treatment Outcome , Urinary Bladder Neoplasms/surgery
6.
Urology ; 137: 26-32, 2020 03.
Article in English | MEDLINE | ID: mdl-31893532

ABSTRACT

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.


Subject(s)
Anxiety/psychology , Prostate/pathology , Prostatic Neoplasms/pathology , Aged , Anxiety/etiology , Diaphragm , Humans , Image-Guided Biopsy/methods , Image-Guided Biopsy/psychology , Male , Middle Aged , Preoperative Care/methods , Rectum , Respiration , Ultrasonography, Interventional
7.
Pediatric Health Med Ther ; 10: 75-81, 2019.
Article in English | MEDLINE | ID: mdl-31496864

ABSTRACT

Prune belly syndrome (PBS) is a rare but morbid congenital disease, classically defined by a triad of cardinal features that includes cryptorchidism, urinary tract dilation and laxity of the abdominal wall musculature. Children often require numerous surgical interventions including bilateral orchidopexy as well as individually tailored urinary tract and abdominal wall reconstruction. Along with the classic features, patients with PBS often experience gastrointestinal, orthopedic, and cardiopulmonary comorbidities.

8.
Am J Surg Pathol ; 43(10): 1413-1420, 2019 10.
Article in English | MEDLINE | ID: mdl-31335354

ABSTRACT

Tumor size has been used for decision making in the management of patients with renal masses. Active surveillance in selected patients is now increasingly common in tumors ≤4 cm in size. Clear cell renal cell carcinoma (CCRCC) is the most common type of renal malignancy. Adverse histopathologic characteristics that correlate with worse prognosis have been described in CCRCCs. The aim of our study was to determine the frequency and extent of adverse histopathologic characteristics in CCRCCs ≤4 cm and their association with patient outcome. A search of a single institution for nephrectomies performed for CCRCC identified 631 consecutive cases. Cases were reviewed for the following morphologic features: high nuclear grade, necrosis, lymphovascular invasion, and rhabdoid or sarcomatoid histology. Relationships between the variables were examined by Kruskal-Wallis test, Wilcoxon test, χ test, and logistic regression. We found adverse tumor histopathologic characteristics were significantly related to size: In CCRCCs >4 versus ≤4 cm, there were more high nuclear grade (45% vs. 15%, P<0.01), necrosis (46% vs. 21%, P<0.01), and lymphovascular invasion (17% vs. 3%, P<0.01). Although adverse histologic features are less commonly seen in CCRCCs ≤4 cm, their presence was associated with lower disease-free survival (P<0.01). Adverse histopathologic characteristics in CCRCCs ≤4 cm correlated with worse prognosis and identification of these features through needle core biopsy examination may guide clinical management, especially in patients for whom active surveillance is considered.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Tumor Burden , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/surgery , Female , Follow-Up Studies , Humans , Kidney Neoplasms/surgery , Male , Middle Aged , Nephrectomy , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
9.
Urol Oncol ; 35(9): 542.e19-542.e24, 2017 09.
Article in English | MEDLINE | ID: mdl-28501565

ABSTRACT

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.


Subject(s)
Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Prostate/pathology , Ultrasonography/methods , Humans , Male , Middle Aged , Prostatic Neoplasms
10.
Can J Urol ; 24(2): 8759-8764, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28436365

ABSTRACT

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.


Subject(s)
Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Watchful Waiting , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Female , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Retrospective Studies , Survival Rate
11.
Med Image Anal ; 39: 29-43, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28431275

ABSTRACT

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.


Subject(s)
Algorithms , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Ultrasonography/methods , Humans , Imaging, Three-Dimensional/methods , Male , Pattern Recognition, Automated/methods
12.
Urology ; 105: 118-122, 2017 07.
Article in English | MEDLINE | ID: mdl-28322902

ABSTRACT

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.


Subject(s)
Carcinoma/diagnostic imaging , Carcinoma/pathology , Image-Guided Biopsy , Magnetic Resonance Imaging, Interventional , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Cohort Studies , Contrast Media , Diffusion Magnetic Resonance Imaging , Humans , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Prostate-Specific Antigen , Ultrasonography, Interventional
13.
Front Oncol ; 6: 157, 2016.
Article in English | MEDLINE | ID: mdl-27446803

ABSTRACT

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.

14.
Can J Urol ; 23(3): 8271-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27347619

ABSTRACT

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.


Subject(s)
Lymph Node Excision/methods , Neoplasm Recurrence, Local/surgery , Prostatectomy/methods , Prostatic Neoplasms/surgery , Salvage Therapy/methods , Surgical Wound Infection/etiology , Aged , Anastomotic Leak/etiology , Blood Loss, Surgical , Humans , Intraoperative Complications/etiology , Laparoscopy , Lymphatic Metastasis , Male , Margins of Excision , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Pelvis , Prostate-Specific Antigen/blood , Prostatectomy/adverse effects , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Robotic Surgical Procedures , Treatment Outcome
15.
Cancer Med ; 5(8): 2101-8, 2016 08.
Article in English | MEDLINE | ID: mdl-27228559

ABSTRACT

Significant racial disparities in survival for renal cell carcinoma (RCC) exist between white and black patients. Differences in access to care and comorbidities are possible contributors. To investigate if racial disparities persist when controlling for access to care, we analyzed data from a single-payer healthcare system. As part of a case-control study within the Kaiser Permanente Northern California system, pathologic and clinical records were obtained for RCC cases (2152 white, 293 black) diagnosed from 1998 to 2008. Patient demographics, comorbidities, tumor characteristics, and treatment status were compared. Overall survival and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. A Cox proportion hazards model estimated the independent associations of race, comorbidity, and clinicopathologic variables with DSS. We found that compared to white patients, black patients were diagnosed at a younger age (median 62 vs. 66 years, P < 0.001), were more likely to have papillary RCC (15% vs. 5.2%, P < 0.001), and had similar rates of surgical treatment (78.8% vs. 77.9%, P = 0.764). On multivariate analysis, advanced American Joint Committee on Cancer (AJCC) stage, lack of surgical treatment, larger tumor size, and higher grade were predictors of worse DSS. Race was not an independent predictor of survival. Therefore, we conclude that within a single healthcare system, differences in characteristics of black and white patients with RCC persist; black patients had different comorbidities, were younger, and had decreased tumor stage. However, unlike other series, race was not an independent predictor of DSS, suggesting that survival differences in large registries may result from barriers to healthcare access and/or comorbidity rather than disease biology.


Subject(s)
Carcinoma, Renal Cell/epidemiology , Ethnicity , Healthcare Disparities , Kidney Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , California/epidemiology , California/ethnology , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/therapy , Case-Control Studies , Comorbidity , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Male , Middle Aged , SEER Program , Survival Analysis
16.
Proc Natl Acad Sci U S A ; 113(8): 2170-5, 2016 Feb 23.
Article in English | MEDLINE | ID: mdl-26864202

ABSTRACT

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.


Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Mutation , Aged , Carcinoma, Renal Cell/classification , Cell Dedifferentiation/genetics , DNA Mismatch Repair/genetics , DNA-Binding Proteins , Exome , Female , Genes, p53 , Humans , Kidney Neoplasms/classification , Loss of Heterozygosity , Male , Middle Aged , Nuclear Proteins/genetics , Oncogenes , Polymorphism, Single Nucleotide , Prognosis , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics
17.
J Trauma Acute Care Surg ; 77(6): 879-85; discussion 885, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25248064

ABSTRACT

BACKGROUND: Blunt abdominal aortic injury (BAAI) is a rare injury. The objective of the current study was to examine the presentation and management of BAAI at a multi-institutional level. METHODS: The Western Trauma Association Multi-Center Trials conducted a study of BAAI from 1996 to 2011. Data collected included demographics, injury mechanism, associated injuries, interventions, and complications. RESULTS: Of 392,315 blunt trauma patients, 113 (0.03%) presented with BAAI at 12 major trauma centers (67% male; median age, 38 years; range, 6-88; median Injury Severity Score [ISS], 34; range, 16-75). The leading cause of injury was motor vehicle collisions (60%). Hypotension was documented in 47% of the cases. The most commonly associated injuries were spine fractures (44%) and pneumothorax/hemothorax (42%). Solid organ, small bowel, and large bowel injuries occurred in 38%, 35%, and 28% respectively. BAAI presented as free aortic rupture (32%), pseudoaneurysm (16%), and injuries without aortic external contour abnormality on computed tomography such as large intimal flaps (34%) or intimal tears (18%). Open and endovascular repairs were undertaken as first-choice therapy in 43% and 15% of cases, respectively. Choice of management varied by type of BAAI: 89% of intimal tears were managed nonoperatively, and 96% of aortic ruptures were treated with open repair. Overall mortality was 39%, the majority (68%) occurring in the first 24 hours because of hemorrhage or cardiac arrest. The highest mortality was associated with Zone II aortic ruptures (92%). Follow-up was documented in 38% of live discharges. CONCLUSION: This is the largest BAAI series reported to date. BAAI presents as a spectrum of injury ranging from minimal aortic injury to aortic rupture. Nonoperative management is successful in uncomplicated cases without external aortic contour abnormality on computed tomography. Highest mortality occurred in free aortic ruptures, suggesting that alternative measures of early noncompressible torso hemorrhage control are warranted. LEVEL OF EVIDENCE: Epidemiologic study, level III; therapeutic study, level IV.


Subject(s)
Aorta, Abdominal/injuries , Wounds, Nonpenetrating/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/surgery , Child , Female , Humans , Injury Severity Score , Length of Stay/statistics & numerical data , Male , Middle Aged , Multiple Trauma/epidemiology , Radiography , Retrospective Studies , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/diagnostic imaging , Wounds, Nonpenetrating/therapy , Young Adult
18.
J Trauma Acute Care Surg ; 75(6): 1013-7; discussion 1017-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24256675

ABSTRACT

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.


Subject(s)
Abdominal Injuries/diagnosis , Laparoscopy/methods , Trauma Centers , Wounds, Stab/diagnosis , Abdominal Injuries/mortality , Abdominal Injuries/surgery , Adult , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Survival Rate/trends , Trauma Severity Indices , United States/epidemiology , Wounds, Stab/mortality , Wounds, Stab/surgery
19.
Am J Orthop (Belle Mead NJ) ; 41(12): 565-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23431527

ABSTRACT

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.


Subject(s)
Embolism, Fat/diagnosis , Tibial Fractures/complications , Adolescent , Embolism, Fat/etiology , Embolism, Fat/therapy , Fibula/injuries , Fracture Fixation, Intramedullary , Humans , Male , Tibial Fractures/surgery
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