Publications by authors named "Kenneth A Iczkowski"

Aims: In radical prostatectomy (RP), Grade Group (GG) 4/5 prostate cancer [high-grade prostate cancer (HGPC) hereafter] is often associated with extension beyond the prostate and positive surgical margins. Hence, there is limited information on post-RP outcomes of patients with completely resected HGPC confined to the prostate (pT2).

Materials And Methods: Clinical outcomes were assessed in a cohort of patients with pT2 HGPC and negative surgical margins using Kaplan-Meier statistics and Cox regression analysis.

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Current prostate cancer risk stratification tools are not adapted for magnetic resonance imaging (MRI)-targeted biopsies and do not include the presence of cribriform carcinoma/intraductal carcinoma (CC/IDC), an independent predictor of adverse clinical outcomes. We developed an MRI-adapted prostate cancer risk tool (MAPCaRT), which incorporates CC/IDC presence to the Cancer of the Prostate Risk Assessment (CAPRA) tool. We compared the prognostic power of MAPCaRT with that of CAPRA in MRI-targeted biopsies (n = 266, 2015-2023) and systematic-only biopsies (n = 1291, 2010-2018) that had matched radical prostatectomy.

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Purpose: Histologic evaluation of prostatic needle biopsies is essential for prostate cancer (PCa) diagnosis and treatment planning, yet tissue targeting remains suboptimal despite MRI-guided Bx procedures. This pilot study investigates the use of label-free Fluorescence Lifetime Imaging (FLIm) for real-time biopsy guidance. Using ex vivo specimens, we assess FLIm's preliminary efficacy in discriminating malignant from benign prostate tissue.

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We present a panel of virtual staining neural networks for lung and heart transplant biopsies, providing rapid and high-quality histological staining results while bypassing the traditional histochemical staining process. Allograft rejection is a common complication of organ transplantation, which can lead to life-threatening outcomes if not promptly managed. Histological examination is the gold standard method for evaluating organ transplant rejection status, as it provides detailed insights into rejection signatures at the cellular level.

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Purpose: This study investigates the potential of DALL·E 3, an artificial intelligence (AI) model, to generate synthetic pathologic images of prostate cancer (PCa) at varying Gleason grades. The aim is to enhance medical education and research resources, particularly by providing diverse case studies and valuable teaching tools.

Methods: This study uses DALL·E 3 to generate 30 synthetic images of PCa across various Gleason grades, guided by standard Gleason pattern descriptions.

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Working Group 1 at ISUP's Cancer Precursors meeting (September 2024) evaluated 5 putative precursors of invasive prostate cancer: high-grade prostatic intraepithelial neoplasia (HGPIN), intraductal carcinoma (IDC), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/adenosis, and proliferative inflammatory atrophy (PIA). Objectives were to compile recent evidence, interrogate current practices, and vote on recommendations, with 67% approval defined as consensus. Consensus was reached against the reporting of the low-grade form of PIN.

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The androgen receptor (AR) is a pivotal regulator of growth and survival of prostate cancer (PCa) and the majority of lethal castration-resistant prostate cancers (CRPC) remain reliant on AR signaling. PCa exhibits variability in progression and responses to treatment suggesting genetic heterogeneity. Two independent studies identified PCa predisposing single nucleotide polymorphisms (SNPs) within the FAM111A protease gene, but the mechanistic basis of this association remained elusive.

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A significant subset of well-differentiated prostatic acinar neoplasms with invasive histologic features will not spread outside of the prostate, become symptomatic, or shorten a patient's life even if the tumor is left untreated. Overdiagnosis and overtreatment of these indolent prostate cancers (PCa) remain a significant health care problem despite the improved risk assessment and uptake in acceptance of conservative management. While detection of indolent PCa on an entirely resected prostate is possible, recognition of indolent PCa on a needle biopsy (NBX) cannot be reliably made as Grade Group 1 (GG1) PCa diagnosis on NBX is not always identical to one from radical prostatectomy due to a variety of reasons.

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Detection of indolent prostate cancer in contemporary practice is an issue that can result in overtreatment for patients and a financial burden for health care systems. Solutions to this problem require a coordinated multidisciplinary approach involving clinicians, radiologists, and pathologists.

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Following the publication of this paper, a concerned reader drew to the attention of the Editorial Office that, for the photomicrographs shown in Fig. 2B on p. 8, the same image had apparently been selected to represent the images for cerebrum and cerebellum from the brain.

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Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

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Article Synopsis
  • - The study aimed to assess how pathologists report tumor content in prostate cancer biopsies and evaluate consistency among them using 10 standardized cases.
  • - A survey of 304 pathologists revealed that most report tumor extent as a percentage, but there is significant variability in how they calculate these percentages.
  • - The findings indicate high interobserver variability, especially with percentage reporting, suggesting that using absolute measures of tumor content could provide more consistent results for patient prognosis.
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Unlabelled: It is imperative to identify patients with prostate cancer (PCa) who will benefit from androgen receptor signaling inhibitors that can impact quality of life upon prolonged use. Using our extensively-validated artificial-intelligence technique: cellular morphometric biomarker via machine learning (CMB-ML), we identified 13 CMBs from whole slide images of needle biopsies from the trial specimens ( NCT02430480 , n=37) that accurately predicted response to neoadjuvant androgen deprivation therapy (NADT) (AUC: 0.980).

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Article Synopsis
  • A significant portion of prostate cancer cases may have a hereditary link, prompting a study into germline pathogenic variants among patients.
  • Among 160 prostate cancer patients tested, 12% were found to have pathogenic variants in various genes, with no notable differences in clinicopathologic characteristics between those with and without these variants.
  • The study highlighted that patients with a family history of cancer were more likely to possess these genetic variants, suggesting a need for further research with larger samples to explore the connections between genetic and clinical data.
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The purpose of this study was to assess the efficacy, specificity, and predictive value of a newly discovered biomarker, Zinc finger-like1 protein (referred to as neuroendocrine marker, NEM) for the detection of prostate cancer (PCa). We retrospectively analyzed banked plasma samples from 508 men, with a median age of 67 years (range 48-97), to compare the performance of NEM and PSA in predicting subsequent histologic PCa. The cohort consisted of four groups of patients visiting a urology clinic: (1) patients not diagnosed with either benign prostatic disease or prostate cancer (PCa) were defined as normal; (2) patients diagnosed with benign hyperplasia (BPH) but not PCa; (3) patients with confirmed PCa; and (4) patients with cancer other than PCa.

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Article Synopsis
  • * The survey received an 85% response rate from 98 uropathologists, revealing strong agreement on distinguishing between luminal and basal UC types, but varied opinions on the importance of certain genetic tests like FGFR3 and TERT promoter mutations.
  • * Most uropathologists acknowledged the aggressive nature of tumors with micropapillary features and favored further evaluation and specific molecular testing for aggressive subtypes, indicating a need for improved consensus in UC classification and treatment strategies.
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The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs.

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Background: Vasculature plays a crucial role in the progression of prostate cancer (PC). Changes to the prostatic native vessels have not been studied since 2000 when Garcia et al. demonstrated marked media hypercellularity and increased artery thickness in prostatic native arteries within PC.

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Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC).

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Aims: Pre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification.

Methods: A retrospective cohort of treatment-naïve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC.

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Prostate cancer is the most commonly diagnosed cancer in men, accounting for 27% of the new male cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is considered curative; however, distant metastases may occur, resulting in a poor patient prognosis. This study sought to determine whether quantitative pathomic features of prostate cancer differ in patients who biochemically experience biological recurrence after surgery.

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Prostate cancer (PCa) is the most diagnosed non-cutaneous cancer in men. Despite therapies such as radical prostatectomy, which is considered curative, distant metastases may form, resulting in biochemical recurrence (BCR). This study used radiomic features calculated from multi-parametric magnetic resonance imaging (MP-MRI) to evaluate their ability to predict BCR and PCa presence.

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