Publications by authors named "Ashutosh K Tewari"

Background: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic, and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.

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Article Synopsis
  • All cells, regardless of being eukaryotic or prokaryotic, release extracellular vesicles (EVs) for various functions like communication and waste disposal, with small EVs containing small RNAs that may serve as important disease markers.
  • This study focuses on identifying unannotated small RNAs in EVs from prostate cancer and benign tissues, overcoming limitations of previous sequencing methods to explore the 'dark matter' of genomes and their role in gene expression regulation.
  • Researchers found that these novel EV-associated small RNAs, termed EV-UGRs, showed a significant reduction in aggressive prostate cancer, but their expression increased after treatment, potentially promising for fluid-based diagnostics in cancer screening.
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Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes.

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Prostate cancer (PCa) incidence, morbidity, and mortality rates are significantly impacted by racial disparities. Despite innovative therapeutic approaches and advancements in prevention, men of African American (AA) ancestry are at a higher risk of developing PCa and have a more aggressive and metastatic form of the disease at the time of initial PCa diagnosis than other races. Research on PCa has underlined the biological and molecular basis of racial disparity and emphasized the genetic aspect as the fundamental component of racial inequality.

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The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors on NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression by cancer cells can be targeted for MHC-E-restricted T cell control, we immunized rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors genetically programmed to elicit MHC-E-restricted CD8 T cells and to express established tumor-associated antigens (TAAs) including prostatic acidic phosphatase (PAP), Wilms tumor-1 protein, or Mesothelin. T cell responses to all three tumor antigens were comparable to viral antigen-specific responses with respect to frequency, duration, phenotype, epitope density, and MHC restriction.

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Background: Urologic research often requires data abstraction from unstructured text contained within the electronic health record. A number of natural language processing (NLP) tools have been developed to aid with this time-consuming task; however, the generalizability of these tools is typically limited by the need for task-specific training.

Objective: To describe the development and validation of a zero-shot learning NLP tool to facilitate data abstraction from unstructured text for use in downstream urologic research.

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Background: Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging males, affecting 50% of men over 50 and up to 80% of men over 80 years old. Its negative impact on health-related quality of life implores further investigation into its risk factors and strategies for effective management. Although the exact molecular mechanisms underlying pathophysiological onset of BPH are poorly defined, the current hypothesized contributors to BPH and lower urinary tract symptoms (LUTS) include aging, inflammation, metabolic syndrome, and hormonal changes.

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Introduction: The extensive heterogeneity of prostate cancer (PCa) and multilayered complexity of progression to castration-resistant prostate cancer (CRPC) have contributed to the challenges of accurately monitoring advanced disease. Profiling of the tumor microenvironment with large-scale transcriptomic studies have identified gene signatures that predict biochemical recurrence, lymph node invasion, metastases, and development of therapeutic resistance through critical determinants driving CRPC.

Areas Covered: This review encompasses understanding of the role of different molecular determinants of PCa progression to lethal disease including the phenotypic dynamic of cell plasticity, EMT-MET interconversion, and signaling-pathways driving PCa cells to advance and metastasize.

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Article Synopsis
  • - The study evaluated the effects of the Saline-Assisted Fascial Exposure (SAFE) technique on erectile function (EF), urinary continence, and cancer outcomes in patients undergoing Robot-Assisted Laparoscopic Radical Prostatectomy (RALP) from January 2021 to July 2022.
  • - Patients with a baseline Sexual Health Inventory for Men (SHIM) score of ≥17 and high risk of extracapsular extension were included, comparing outcomes between those who had the SAFE technique alongside RALP (33 patients) and those who had just RALP (66 patients).
  • - Results indicated significantly improved SHIM scores and higher EF rates in the RALP + SAFE group at multiple follow-up intervals,
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Objective: To provide a systematic summary of prospectively performed studies evaluating ablative therapies for the treatment of prostate cancer (PCa) that included protocol-mandated assessment of (1) residual disease by post-treatment biopsy and/or (2) erectile functional outcomes.

Materials And Methods: We performed a comprehensive literature search in September 2022. Studies were evaluated according to a predefined and registered plan in PROSPERO (CRD42022302777).

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  • * There is growing excitement around using these therapies for localized or locally advanced genitourinary (GU) cancers to help lower recurrence rates and boost survival outcomes.
  • * Although neoadjuvant therapies were once standard for bladder cancer, they are currently being tested in clinical trials for renal and prostate cancers, with future advancements expected through precision medicine guided by biomarkers.
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Large language models such as ChatGPT are poised to transform health care. We envision them being used in the future in urology, albeit with appropriate supervision, to educate patients, guide clinicians and scientists, and automate complex tasks.

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Introduction: Urinary incontinence is one of the most common long term side effects after robotic prostatectomy (RALP), and significantly impacts patient quality of life. Pelvic floor muscle training (PFMT) has been a standard part of the urologist's armamentarium for maximizing continence outcomes post-op. Recently, aerobic and resistance exercises have been described as improving functional outcomes post RALP.

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Background: Radiohybrid (rh) F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging.

Objective: To evaluate the diagnostic performance and safety of F-rhPSMA-7.

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Background: An informed decision regarding a treatment option requires data on its long-term efficacy and side-effect profile. While the side-effects of robotic radical prostatectomy have been well-quantified, the data on its long-term efficacy are lacking. We here provide 15-year oncological outcomes of clinically-localized prostate cancer (CLPCa) patients treated with robot-assisted laparoscopic prostatectomy (RALP).

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  • The study aimed to explore the link between genomic characteristics of connective tissue and negative clinical outcomes in patients who underwent radical prostatectomy for localized prostate cancer.
  • A retrospective analysis of 695 patients revealed significant variations in the expression of selected connective tissue genes, indicating a correlation with clinical features like extra-capsular extension (ECE), lymph node (LN) invasion, and early biochemical recurrence (eBCR).
  • Results showed that higher Decipher scores, associated with gene overexpression, correlated with worse progression-free survival (PFS) and clinical conditions, highlighting the potential prognostic significance of connective tissue gene expression in prostate cancer.
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Background And Objective: Multi-photon microscopy (MPM) is a 3-dimension fluorescence imaging technique that combines the excitation of two low-energy photons, enabling less photo-bleaching and deeper penetration of the imaged tissue. Two signals are detected, autofluorescence (AF), from natural intracellular fluorophores [such as nicotinamide adenine dinucleotide phosphate (NADP) and flavine adenine dinucleotide (FAD) transformation], and second harmonic generation (SHG), a physical property of the laser enhancing non-centrosymmetric structures such as collagen fibers. MPM can give both visual and quantitative information of a fresh tissue (without the need of processing, cutting or staining the tissue), aiding in the progress towards optimizing a real-time imaging device.

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Background: Prediction of extracapsular extension (ECE) is essential to achieve a balance between oncologic resection and neural tissue preservation. Microultrasound (MUS) is an attractive alternative to multiparametric magnetic resonance imaging (mpMRI) in the staging scenario.

Objective: To create a side-specific nomogram integrating clinicopathologic parameters and MUS findings to predict ipsilateral ECE and guide nerve sparing.

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The diagnosis of prostate cancer (PCa) depends on the evaluation of core needle biopsies by trained pathologists. Artificial intelligence (AI) derived models have been created to address the challenges posed by pathologists' increasing workload, workforce shortages, and variability in histopathology assessment. These models with histopathological parameters integrated into sophisticated neural networks demonstrate remarkable ability to identify, grade, and predict outcomes for PCa.

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Kidney stones are one of the most common renal pathologies. While emerging evidence has implicated a potential association between kidney stones and upper urinary tract cancers (including renal cancer), there is limited understanding as to the common underlying biological pathways functionally linking the etiology of kidney stone formation and the incidence, development, and progression of urinary tract cancers. From a clinical perspective, kidney stone disease can be a barrier to oncologic care due to renal obstruction.

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In the United States, African American (AA) men have a 2.4 times higher mortality rate due to prostate cancer than White men. The multifactorial causes of the racial disparities in prostate cancer involve various social determinants of health, socioeconomic status, and access to healthcare.

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