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1.
Sensors (Basel) ; 24(2)2024 Jan 14.
Article in English | MEDLINE | ID: mdl-38257613

ABSTRACT

The use of low-cost sensors (LCSs) for the mobile monitoring of oil and gas emissions is an understudied application of low-cost air quality monitoring devices. To assess the efficacy of low-cost sensors as a screening tool for the mobile monitoring of fugitive methane emissions stemming from well sites in eastern Colorado, we colocated an array of low-cost sensors (XPOD) with a reference grade methane monitor (Aeris Ultra) on a mobile monitoring vehicle from 15 August through 27 September 2023. Fitting our low-cost sensor data with a bootstrap and aggregated random forest model, we found a high correlation between the reference and XPOD CH4 concentrations (r = 0.719) and a low experimental error (RMSD = 0.3673 ppm). Other calibration models, including multilinear regression and artificial neural networks (ANN), were either unable to distinguish individual methane spikes above baseline or had a significantly elevated error (RMSDANN = 0.4669 ppm) when compared to the random forest model. Using out-of-bag predictor permutations, we found that sensors that showed the highest correlation with methane displayed the greatest significance in our random forest model. As we reduced the percentage of colocation data employed in the random forest model, errors did not significantly increase until a specific threshold (50 percent of total calibration data). Using a peakfinding algorithm, we found that our model was able to predict 80 percent of methane spikes above 2.5 ppm throughout the duration of our field campaign, with a false response rate of 35 percent.

2.
Oncologist ; 28(2): 149-156, 2023 02 08.
Article in English | MEDLINE | ID: mdl-35920550

ABSTRACT

INTRODUCTION: This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period. PATIENTS AND METHODS: All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database. Patients were divided into groups based on self-reported race. Grade group progression was defined as pathologic upgrading above International Society of Urological Pathology Grade Group 1 disease on subsequent biopsies following diagnostic biopsy. All tests were 2 sided using a significance of .05. RESULTS: A total of 228 men met inclusion criteria in the study, including 154 non-Hispanic African American and 74 non-Hispanic Caucasian American men, with a median follow-up of 5 years from the initiation of AS. Race was not predictive of Gleason grade progression, AS discontinuation, or biochemical recurrence on Cox multivariate analysis (HR = 1.01, 0.94, 0.85, P = .96, .79, .81, respectively). On Kaplan-Meier analysis at 5 years, African-American progression-free, AS discontinuation free, and overall survival probability was comparable to their Caucasian American counterparts (P > .05 for all). CONCLUSIONS: Active surveillance is a safe treatment option for low and very low risk prostate cancer, regardless of race. African-American and Caucasian-American men did not have any significant difference in Gleason grade group progression in our cohort with 5-year follow-up.


Subject(s)
Black or African American , Prostatic Neoplasms , Male , Humans , Watchful Waiting , Prostatic Neoplasms/pathology , Neoplasm Grading , Prospective Studies , Prostate-Specific Antigen
3.
Epilepsy Behav Rep ; 19: 100560, 2022.
Article in English | MEDLINE | ID: mdl-35856042

ABSTRACT

We report a female child with PCDH19 related developmental and epileptic encephalopathy with drug-resistant seizures, cognitive and language impairment, autism spectrum disorder and sleep dysfunction. Her seizures, which started at 10 months of age, were resistant to multiple anti-seizure medications. Developmental stagnation followed by regression occurred after the onset of recurrent seizures. Her ictal EEGS suggested left temporal lobe origin for her recorded seizures. MRI upon expert re-review showed a subtle abnormality in the left temporal lobe. In view of the severe nature and frequency of her seizures, a left temporal lobectomy was undertaken at the age of 2 years and 3 months. Though her seizure outcome was Engel class 3, her seizure frequency and severity were significantly reduced. She has been seizure-free for 10 months at her last outpatient assessment when she was 4 years and 8 months of age (2 years and 5 months after epilepsy surgery). However she recently had an admission for COVID19 infection, with a breakthrough cluster of seizures. Her developmental trajectory changed, though she is making good progress with her cognitive and language skills.

4.
JAMA Oncol ; 8(8): 1128-1136, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35708696

ABSTRACT

Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. Design, Setting, and Participants: The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites. Eligible patients were 18 years or older, had received a diagnosis of histologically proven low-risk or intermediate-risk localized prostate cancer within 6 months of screening, and were undergoing AS. Patients were monitored during 1 year of treatment and up to 2 years of follow-up. Data analysis was conducted in February 2021. Interventions: Randomized 1:1 to enzalutamide, 160 mg, monotherapy for 1 year or continued AS, as stratified by cancer risk and follow-up biopsy type. Main Outcomes and Measures: The primary end point was time to pathological or therapeutic prostate cancer progression (pathological, ≥1 increase in primary or secondary Gleason pattern or ≥15% increased cancer-positive cores; therapeutic, earliest occurrence of primary therapy for prostate cancer). Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, and incidence of a secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression. Adverse events were monitored to assess safety. Results: A total of 114 patients were randomized to treatment with enzalutamide plus AS and 113 to AS alone; baseline characteristics were similar between treatment arms (mean [SD] age, 66.1 [7.8] years; 1 Asian individual [0.4%], 21 Black or African American individuals [9.3%], 1 Hispanic individual [0.4%], and 204 White individuals [89.9%]). Enzalutamide significantly reduced the risk of prostate cancer progression by 46% vs AS (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). Compared with AS, odds of a negative biopsy result were 3.5 times higher; there was a significant reduction in the percentage of cancer-positive cores and the odds of a secondary rise in serum PSA levels at 1 year with treatment with enzalutamide; no significant difference was observed at 2 years. Treatment with enzalutamide also significantly delayed PSA progression by 6 months vs AS (hazard ratio, 0.71; 95% CI, 0.53-0.97; P = .03). The most commonly reported adverse events during enzalutamide treatment were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three patients in the enzalutamide arm died; none were receiving the study drug at the time of death. No deaths were considered treatment-related. Conclusions and Relevance: The results of this randomized clinical trial suggest that enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing AS. Trial Registration: ClinicalTrials.gov Identifier: NCT02799745.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Aged , Benzamides/pharmacology , Benzamides/therapeutic use , Canada , Humans , Male , Middle Aged , Nitriles/pharmacology , Nitriles/therapeutic use , Phenylthiohydantoin/pharmacology , Phenylthiohydantoin/therapeutic use , Prostate-Specific Antigen , Prostatic Neoplasms/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Treatment Outcome , Watchful Waiting
5.
JNCI Cancer Spectr ; 6(1)2022 02.
Article in English | MEDLINE | ID: mdl-35079693

ABSTRACT

Background: Altered DNA damage response (DDR) has emerged as an important mechanism for the development of aggressive prostate cancer among men of European ancestry but not other ancestry groups. Because common mechanisms for aggressive disease are expected, we explored a large panel of DDR genes and pathways to demonstrate that DDR alterations contribute to development of aggressive prostate cancer in both African American and European American men. Methods: We performed a case-case study of 764 African American and European American men with lethal or indolent prostate cancer treated at 4 US hospitals. We calculated carrier frequencies of germline pathogenic or likely pathogenic sequence variants within 306 DDR genes, summarized by DDR pathway, and compared lethal cases against indolent cases using 2-sided Fisher's exact tests. Secondary analysis examined if carrier frequencies differed by ancestry. Results: Lethal cases were more likely to carry a pathogenic sequence variant in a DDR gene compared with indolent cases (18.5% vs 9.6%, P = 4.30 × 10-4), even after excluding BRCA2 (14.6% vs 9.6%, P = .04). The carrier frequency was similar among lethal cases of African (16.7% including and 15.8% excluding BRCA2) and lethal cases of European (19.3% including and 14.2% excluding BRCA2) ancestry. Three DDR pathways were statistically significantly associated with lethal disease: homologous recombination (P = .003), Fanconi anemia (P = .002), and checkpoint factor (P = .02). Conclusions: Our findings suggest that altered DDR is an important mechanism for aggressive prostate cancer not only in men of European but also of African ancestry. Therefore, interrogation of entire DDR pathways is needed to fully characterize and better define genetic risk of lethal disease.


Subject(s)
Black or African American/genetics , DNA Repair-Deficiency Disorders/genetics , DNA Repair/genetics , Prostatic Neoplasms/genetics , White People/genetics , Aged , DNA Mismatch Repair/genetics , Fanconi Anemia/genetics , Humans , Male , Middle Aged , Prostatic Neoplasms/ethnology
6.
Curr Oncol ; 28(4): 2308-2316, 2021 06 22.
Article in English | MEDLINE | ID: mdl-34206419

ABSTRACT

African American (AA) men have increased risk of prostate cancer diagnosis and mortality, but the cause remains unknown. MRI fusion improves diagnosis of localized prostate cancer, particularly in anterior lesions; however, cost and access are limited in a community practice setting. By utilizing a diverse cohort of veterans with equal access to care in a single payer system, we describe prostate cancer detection. We queried a prospectively maintained institutional review board-approved database of men undergoing prostate biopsy for untreated prostate cancer. We included all consecutive patients from October 2017 to February 2020. Statistical analysis including Kaplan-Meier Curves, Fisher's exact test, and Forest plot was performed. From 246 consecutive patients, 166 were AA and 80 were non-AA. There were similar distributions of PSA, PSAD, and number of targetable lesions between the AA and non-AA cohort (p > 0.05 for all). We found no difference in location on MRI between race groups. There was similar cancer detection, focusing on anterior lesions and rate of positive Gleason grade (≥GG1) and clinically significant (≥GG2) cancer between cohorts. In a predominant AA cohort of veterans, we found similar distribution of location for MRI-targeted lesions, along with rates of tumor detection and aggressiveness of disease. In this single payer veteran population, we did not identify specific biologic differences inherent to tumor detection between AA and non-AA patients.


Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Black or African American , Humans , Male , Prostate-Specific Antigen , Prostatic Neoplasms/diagnostic imaging , Race Factors
7.
Urology ; 148: 210, 2021 02.
Article in English | MEDLINE | ID: mdl-33549217
8.
Urology ; 148: 203-210, 2021 02.
Article in English | MEDLINE | ID: mdl-33166542

ABSTRACT

OBJECTIVE: To evaluate the risk upgrading of active surveillance (AS), we reviewed the outcomes of African American men (AA) after electing AS. AS is the standard of care for men with low-grade prostate cancer (PCa). AA are known to have more advanced PCa features and are more likely to die from PCa, thus subsequent disease progression for AA on AS is unclear. METHODS: A prospectively maintained AS database from the Southeast Louisiana Veterans Administration Medical Center, New Orleans, Lousiana was queried. We identified men with low- and very low-risk PCa (Gleason 3 + 3, PSA <10, ≤CT2a) who had undergone at least 2 prostate biopsies, including initial diagnostic and subsequent confirmatory prostate biopsies. Descriptive and comparative statistical analysis was performed using R version 3.5.1. RESULTS: From a total of 274 men on AS (70% AA), 158 men met inclusion criteria (104 AA [66%]). All patients underwent at least 2 biopsies, and 29% underwent 3 or more biopsies. The median follow-up was 2.7 years. At 3 years on AS protocol, 57% AA and 61% Caucasians demonstrated no evidence of upgrading or treatment. No significant difference was observed between upgrading or progression to treatment when comparing racial groups. Seven (4%) patients in this cohort died from non PCa-specific causes, but no patients demonstrated metastasis or death from PCa over the course of study. CONCLUSION: AA men with low-risk PCa can be safely followed with the same AS protocol as non-AA men. Further analysis with longer follow up is ongoing.


Subject(s)
Black or African American , Prostatic Neoplasms , Watchful Waiting , White People , Humans , Male , Middle Aged , Prospective Studies , Prostatic Neoplasms/therapy , Risk Assessment
9.
Aging Male ; 23(5): 1400-1408, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32500781

ABSTRACT

INTRODUCTION: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are useful clinical biomarkers for prognosis in several malignancies. Their predictive value has been less clearly demonstrated with prostate cancer (PCa), particularly, their utility within active surveillance (AS) protocols. We aim to evaluate NLR and PLR in AS patients. METHODS: We identified 98 patients who met inclusion criteria in our cohort of 274 men diagnosed with PCa on AS. Patients were then categorized into high and low NLR and PLR groups. RESULTS: The 2.5 and 5-year Gleason upgrading free probability for our high NLR cohort was 73.9%(CI 56.3% to 97.0%) and 46.2%(CI 22.4% to 95.1%) compared to 76.3%(CI 65.7% to 88.7%) and 61.7%(CI 47.7% to 80.0%) in the low NLR cohort(p = .73). The 2.5 and 5-year Gleason upgrading free probability for our High PLR cohort was 73.5%(CI 57.3% to 94.2%) and 60.1(CI 41.4% to 87.4%) compared to 76.8%(CI 65.8% to 89.65) and 58.1%(CI 42.2% to 80.1%) in our low PLR group(p = .41). A multivariant analysis demonstrated these groups were not significant predictors of upgrading or treatment. CONCLUSION: Despite their usefulness in many types of malignancy, NLR and PLR were not predictors of upgrading or treatment in men on AS for localized PCa in our cohort.


Subject(s)
Prostatic Neoplasms , Watchful Waiting , Humans , Lymphocytes , Male , Prognosis , Prospective Studies , Retrospective Studies
10.
Cancer Treat Res Commun ; 24: 100177, 2020.
Article in English | MEDLINE | ID: mdl-32454387

ABSTRACT

BACKGROUND: Although emerging evidence demonstrates increased risk of secondary bladder cancer following pelvic radiotherapy, the aggressiveness of these tumors is not well-characterized. MATERIALS AND METHODS: A search of the Surveillance, Epidemiology, and End Results (SEER) 18 Database, identified 25,734 patients diagnosed with bladder cancer following definitive therapy for previous pelvic malignancy. Kaplan-Meier curve analyses were utilized to determine overall survival with significance set at p<0.05. RESULTS: Of the 25,734 patients, 11,376 (44.2%) received radiation treatment for their first cancer. Overall survival of bladder cancer was found to be 80%, 69.5%, and 49.2% at 1,2 and 5 years, respectively. There was no significant survival difference between groups whose first cancer was treated with or without radiation (p=0.8). A survival advantage was seen for the bladder cancer patients not treated with radiation for cervical (p=0.004), uterine (p=0.0006), and vaginal cancers (p<0.0001). Bladder cancer patients treated with radiation for prostate cancer showed a survival advantage (p=0.002). The average time to second cancer diagnosis was 6.5±6.1 years. Patients treated with radiation for first primary cancer showed a longer time to second cancer (7.2±6.0 years) compared to those treated without radiation (5.9±6.0 years) (p<0.01). CONCLUSION: Patients with prior history of female cancers treated without radiation demonstrated significant survival advantage in second primary bladder cancer. A small significant survival advantage was seen in bladder cancer patients previously treated for prostate cancer with radiation. This data suggests that second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy. MICROABSTRACT: The overall survival of 25,734 patients diagnosed with bladder cancer following definitive therapy for a previous pelvic malignancy was 49.2% at 5 years. There was no significant survival difference between groups whose first cancer was treated with or without radiation. Second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy.


Subject(s)
Carcinoma, Transitional Cell/mortality , Neoplasms, Radiation-Induced/mortality , Neoplasms, Second Primary/mortality , Urinary Bladder Neoplasms/mortality , Aged , Carcinoma, Transitional Cell/etiology , Carcinoma, Transitional Cell/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasms, Radiation-Induced/etiology , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/pathology , Prognosis , Prostatic Neoplasms/therapy , Radiotherapy, Adjuvant/adverse effects , Retrospective Studies , SEER Program/statistics & numerical data , Time Factors , Urinary Bladder/pathology , Urinary Bladder/radiation effects , Urinary Bladder Neoplasms/etiology , Urinary Bladder Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Uterine Neoplasms/therapy , Vaginal Neoplasms/therapy
12.
J Robot Surg ; 14(4): 615-619, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31586270

ABSTRACT

Development of ureteroanastamotic strictures (UAS) after urinary diversion is not uncommon, but is challenging to treat. Poor outcomes are likely with endoscopic and radiologic management, and definitive surgical treatment can cause significant morbidity. The comparative advantages of an operative approach have not yet been fully described in the literature. We retrospectively reviewed the prospectively maintained Tulane University Department of Urology quality assurance database of 12 patients who underwent operative UAS repair between 2012 and 2018. Data were reviewed for operative approach, demographics, baseline disease characteristics, operative variables, and perioperative and pathological outcomes. Of the 12 patients analyzed, 5 underwent open repair (OR) (2 bilateral, 2 right, 1 left) and 7 underwent robotic repair (RR) (3 right, 4 left). One robotic case required conversion to open due to significant intestinal and peri-ureteral adhesions. The median ages were 59 years in OR and 60 years in RR. Two patients in each group had failed previous endoscopic repair. Median time from cystectomy to treatment of enteroanastamotic stricture was 13 months for OR and 10 months for RR (p = 0.25). Median estimated blood loss was 80 mL in both OR and RR (p = 1.0), median operative time was 260 min in OR and 255 min in RR (p = 0.13), and median hospital stay was 8 and 4 days, respectively (p = 0.06). There were two intra-operative and one post-operative complication in the OR group, one of whom required further surgical intervention, and no complications in the robotic cohort. A minimally invasive, robotic approach offers a non-inferior alternative to OR with similar outcomes for appropriately selected patients with UAS. High success rates combined with minimal morbidity may provide definitive therapy at an earlier stage of the stricture state.


Subject(s)
Anastomosis, Surgical/adverse effects , Cystectomy/adverse effects , Minimally Invasive Surgical Procedures/methods , Postoperative Complications/etiology , Postoperative Complications/surgery , Robotic Surgical Procedures/methods , Ureter/surgery , Ureteral Obstruction/etiology , Ureteral Obstruction/surgery , Urinary Diversion/adverse effects , Aged , Cohort Studies , Constriction, Pathologic , Data Analysis , Female , Humans , Male , Middle Aged , Quality Assurance, Health Care , Retrospective Studies , Treatment Outcome , Ureter/pathology , Urinary Bladder Neoplasms/surgery
13.
Clin Genitourin Cancer ; 17(5): 380-388, 2019 10.
Article in English | MEDLINE | ID: mdl-31395362

ABSTRACT

INTRODUCTION: The objective of this study was to characterize the demographic, prognostic, and treatment factors for patients with primary adenocarcinoma of the bladder by analyzing the impact of histologic subtype in a large sample size and interpreting newly released Surveillance, Epidemiology, and End Results (SEER) chemotherapy data. MATERIALS AND METHODS: The SEER 18 Registry was utilized to identify cases of primary adenocarcinoma diagnosed from 1973 to 2015. Demographic data, tumor and disease characteristics, treatment information, and survival outcome data were collected. Overall survival and disease-specific survival were determined using Kaplan-Meier curve analysis. Univariate and multivariate Cox regression analysis were then completed using SAS JMP. RESULTS: A total of 2305 cases of primary adenocarcinoma of the bladder were identified. Overall survival at 2-, 5- and 10-year intervals was 54.8%, 36.1%, and 25.4%, respectively. Disease-specific survival at 2-, 5- and 10-year intervals was 62.0%, 47.1%, and 40.1%, respectively. Patients were treated with surgery (86.4%), chemotherapy (21.9%), and radiation (15.0%) (P < .0001). Multivariate Cox regression analysis showed independent prognostic value for gender, stage, grade, primary tumor location, and histologic subtype. The urachus/dome location conferred survival advantage over non-urachal locations on univariable and multivariable Cox regression analysis. The papillary adenocarcinoma subtype conferred the best survival outcome, whereas signet cell carcinoma (hazard ratio, 2.069; P < .0001) and unclassified adenocarcinoma (not otherwise specified) (hazard ratio, 1.524; P < .0001) conferred the worst prognoses. CONCLUSION: This study utilized a population-based analysis to showcase the utility of various prognostic features in primary bladder adenocarcinoma cases. In characterizing treatments, we find the prevailing treatment remains surgical intervention, whereas a sizable minority receives chemotherapy and/or radiation, often in combination with surgery.


Subject(s)
Adenocarcinoma/epidemiology , Adenocarcinoma/therapy , Carcinoma, Signet Ring Cell/mortality , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/therapy , Adenocarcinoma/pathology , Aged , Carcinoma, Papillary/epidemiology , Carcinoma, Papillary/pathology , Carcinoma, Papillary/therapy , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/therapy , Combined Modality Therapy/statistics & numerical data , Demography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , SEER Program , Survival Rate , United States/epidemiology , Urinary Bladder Neoplasms/pathology
14.
Oncogene ; 38(45): 7060-7072, 2019 11.
Article in English | MEDLINE | ID: mdl-31409897

ABSTRACT

Deregulated expression of circular RNAs (circRNAs) is associated with various human diseases, including many types of cancer. Despite their growing links to cancer, there has been limited characterization of circRNAs in metastatic castration-resistant prostate cancer, the major cause of prostate cancer mortality. Here, through the analysis of an exome-capture RNA-seq dataset from 47 metastatic castration-resistant prostate cancer samples and ribodepletion and RNase R RNA-sequencing of patient-derived xenografts (PDXs) and cell models, we identified 13 circRNAs generated from the key prostate cancer driver gene-androgen receptor (AR). We validated and characterized the top four most abundant, clinically relevant AR circRNAs. Expression of these AR circRNAs was upregulated during castration-resistant progression of PDXs. The upregulation was not due to global increase of circRNA formation in these tumors. Instead, the levels of AR circRNAs correlated strongly with that of the linear AR transcripts (both AR and AR variants) in clinical samples and PDXs, indicating a transcriptional mechanism of regulation. In cultured cells, androgen suppressed the expression of these AR circRNAs and the linear AR transcripts, and the suppression was attenuated by an antiandrogen. Using nuclear/cytoplasmic fractionation and RNA in-situ hybridization assays, we demonstrated predominant cytoplasmic localization of these AR circRNAs, indicating likely cytoplasmic functions. Overall, this is the first comprehensive characterization of circRNAs arising from the AR gene. With greater resistance to exoribonuclease compared to the linear AR transcripts and detectability of AR circRNAs in patient plasma, these AR circRNAs may serve as surrogate circulating markers for AR/AR-variant expression and castration-resistant prostate cancer progression.


Subject(s)
Gene Expression Regulation, Neoplastic , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , RNA, Circular/genetics , Receptors, Androgen/genetics , Animals , Humans , Male , Mice, SCID , Protein Isoforms , Receptors, Androgen/classification , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
15.
Urology ; 128: 62-65, 2019 Jun.
Article in English | MEDLINE | ID: mdl-29660369

ABSTRACT

OBJECTIVE: To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. MATERIALS AND METHODS: The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). RESULTS: Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) ≤6 PCa and 27 (33%) with GS ≥7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS ≥7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS ≥7 PCa were 78.8% and 94.2%, respectively. CONCLUSION: In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy.


Subject(s)
Biomarkers, Tumor/genetics , Black or African American , Epigenesis, Genetic , Image-Guided Biopsy/methods , Prostate/pathology , Prostatic Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Grading , Prognosis , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/genetics , Reproducibility of Results , Retrospective Studies , United States/epidemiology
16.
J Paediatr Child Health ; 55(7): 789-794, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30407686

ABSTRACT

AIM: A new-onset seizure clinic (NOSC) was established at our hospital in 2011, with the aim to provide accurate diagnosis and appropriate management to children with new-onset seizures or seizure mimics. METHODS: We report on the data analysis of the first 200 children seen in NOSC. A paediatric neurologist or paediatric/neurology trainee under supervision of a neurologist reviewed all the children. A detailed history and clinical examination were undertaken. Electroencephalogram (EEGs) were undertaken prior to clinic review in most emergency departments. Children were classified as 'epilepsy positive' (EP+) or 'epilepsy negative' (EP-) after the first consultation. RESULTS: Of 200 patients, 109 were classified as EP+: generalised epilepsy in 57 of 109, focal in 36, childhood seizure susceptibility syndrome in 26 and epileptic encephalopathy in 5. EEG was available in 192: in 117, it was abnormal - 23 with background abnormalities and 109 with epileptiform activity. Of the 109 patients, 80 were commenced on anti-epileptic drugs (AEDs): 12 were able to come off medication after seizure-free period, 61 were controlled on AEDs and 7 were refractory. Children were followed up for 12-48 months. None of the children had diagnosis revised on follow-up. CONCLUSIONS: This is the first Australian study to report on a large cohort of children from a NOSC. An EEG and a paediatric neurologist assessment is a good combination to enable diagnostic accuracy: In the first 200 patients seen, there were no revisions of the initial diagnosis on follow-up.


Subject(s)
Electroencephalography/methods , Seizures/diagnosis , Seizures/epidemiology , Age Distribution , Age of Onset , Australia , Child , Child, Preschool , Cohort Studies , Databases, Factual , Female , Hospitals, Pediatric/organization & administration , Humans , Incidence , Male , Neuroimaging/methods , Retrospective Studies , Risk Assessment , Seizures/therapy , Severity of Illness Index , Sex Distribution , Tertiary Care Centers/organization & administration
17.
Transl Androl Urol ; 7(Suppl 4): S397-S410, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30363480

ABSTRACT

Active surveillance (AS) is a treatment modality for prostate cancer that aims to simultaneously avoid overtreatment and allow for the timely intervention of localized disease. AS has become the de facto standard of care for most men with low-risk prostate cancer. However, few African American (AA) men were included in the prospective observational cohorts that resulted in a paradigm shift in treatment recommendations from active intervention toward AS. It has been established that AA men have an increased prostate cancer incidence, higher baseline prostate-specific antigen (PSA) values, more aggressive prostate cancer features, greater frequency of biochemical recurrence after treatment, and higher overall cancer-specific mortality compared to their Caucasian counterparts. As such, this has given many physicians pause before initiating AS for AA patients. In the following manuscript, we will review the available literature regarding AS, with a particular focus on AA men. The preponderance of evidence demonstrates that AS is as viable a management method for AA with low-risk prostate cancer as it is with other racial groups.

18.
J Robot Surg ; 12(1): 27-33, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28108975

ABSTRACT

To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.


Subject(s)
Kidney Neoplasms/surgery , Printing, Three-Dimensional , Robotic Surgical Procedures/education , Aged , Feasibility Studies , Female , Humans , Kidney Neoplasms/diagnostic imaging , Male , Middle Aged , Models, Anatomic , Preoperative Care , Robotic Surgical Procedures/methods , Simulation Training/methods , Tomography, X-Ray Computed
19.
Psychooncology ; 27(3): 810-816, 2018 03.
Article in English | MEDLINE | ID: mdl-29125208

ABSTRACT

OBJECTIVE: To evaluate the relationship between personality and emotional distress in prostate cancer. Neuroticism and introversion were hypothesized to be associated with clinically significant symptoms of emotional distress, including depression, anxiety, and suicidal ideation. METHODS: Men with a history of prostate cancer (n = 212) completed an NIH-funded cross-sectional study using well-validated measures of personality, depression, anxiety, and suicidal ideation. Covariates were age, education, time since diagnosis, comorbidity, and presence of metastases. RESULTS: Emotional distress was reported by 37% of participants, including depression (23%), anxiety (15%), and suicidal ideation (10%). As hypothesized, men who were more neurotic were more likely to report emotional distress (44.5% vs 26.9%; OR = 2.78, P = .004), depression (31.9% vs 11.8%; OR = 4.23, P = .001), and suicidal ideation (29.4% vs 9.7%; OR = 4.15, P = .001). Introverts were more likely to report emotional distress (45.2% vs 28.7%; OR = 2.32, P = .012) and depression (30.8% vs 15.7%; OR = 2.57, P = .014). Men with metastases were more likely to report emotional distress (51.7% vs 31.2%; OR = 4.56, P < .001). CONCLUSIONS: Neuroticism and introversion were associated with clinically significant emotional distress in men with prostate cancer. Findings suggest that, in the context of treatment for prostate cancer, patient distress reflects disease characteristics (eg, metastases presence) as well as stable personality traits. Implications for clinical care are discussed.


Subject(s)
Anxiety/psychology , Depression/psychology , Personality , Prostatic Neoplasms/psychology , Rumination, Cognitive , Suicidal Ideation , Adult , Aged , Cross-Sectional Studies , Humans , Male , Middle Aged , Risk Factors
20.
J Urol ; 199(6): 1459-1463, 2018 06.
Article in English | MEDLINE | ID: mdl-29223389

ABSTRACT

PURPOSE: The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation. MATERIALS AND METHODS: Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men. RESULTS: Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group. CONCLUSIONS: The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men.


Subject(s)
Adenocarcinoma/diagnosis , Biomarkers, Tumor/blood , Black or African American/statistics & numerical data , Prostate/pathology , Prostatic Neoplasms/diagnosis , Adenocarcinoma/blood , Adenocarcinoma/pathology , Aged , Biopsy , Clinical Decision-Making , Hospitals, Veterans/statistics & numerical data , Humans , Male , Middle Aged , Neoplasm Grading , Patient Selection , Predictive Value of Tests , Prognosis , Prospective Studies , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Risk Assessment/methods , United States , United States Department of Veterans Affairs
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