Automated decision algorithms in prostate cancer

A diagnostic decision support system (DDSS) is defi ned as a methodology that provides guidance in situations involving complex decision sequences. DDSSs result in a systematic, ordered, and exhaustive evaluation of evidence and weighting of individual items of evidence as they are combined to form the basis for a fi nal decision. Most DDSSs provide a numeric measure of confi dence in the fi nal decision or diagnostic recommendation. Th e decisive advantage of DDSSs is the ability to process descriptive symbolic information, in contrast to systems limited to the handling of numerical information only for which extensive analytical procedures are already established. Most human knowledge and insight related to diagnostic and prognostic evaluation exist in symbolic form as concepts and linguistic terms, so the DDSSs have facilitated systematic evaluation of evidence to provide diagnostic and prognostic decision support. DDSSs may be implemented as inference networks (or Bayesian Belief Networks – BBNs), automated reasoning systems, case-based reasoning systems, or expert systems. In inference networks and automated reasoning systems, the emphasis is on uncertainty assessment of a given decision sequence. In case-base reasoning, the emphasis is on prognostic assessment for an individual patient. In expert systems, the emphasis is on diagnostic or prognostic assessment, by making available a comprehensive knowledge base of facts and professional experience. However, even though the emphasis is slightly diff erent in these kinds of decision support systems, much of the methodology is shared. A BBN consists of a decision node for the diagnostic alternatives and of evidence nodes for the diagnostic clues. Each clue is observed, rated, and assigned to a function with a given probability. Th e evidence is then forwarded to the decision node via a conditional probability link matrix. At the decision node, the belief in each diagnostic alternative is accumulated. A series of BBNs have already been successfully developed for prostate and non-prostate neoplasms (7-13) including comparing cancer with benign lesions and those with prostatic intraepithelial neoplasms

Molecular diagnostics in uro-oncology.

Research on molecular diagnostics in uro-oncology goes along with the development of complex emerging techniques, ranging from the application of next generation sequencing (NGS) platforms to archi..

Uropathologists During the COVID-19 Pandemic: What Can Be Learned in Terms of Social Interaction, Visibility, and Social Distance

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic

Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine

Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor.' These results were filtered to include manuscripts that focused on diagnostic tests for determining BRAF mutation status. Numerous BRAF testing methods were identified, including DNA-based companion diagnostic tests and DNA- and protein-based laboratory-developed tests. Herein we review the characteristics of each method and highlight the strengths and weaknesses that should be considered before use and when interpreting results for each patient. Molecular profiling has shown that mutation load increases with melanoma tumor progression and that unique patterns of genetic changes and evolutionary trajectories for different melanoma subtypes can occur. Discordance in the BRAF mutational status between primary and metastatic lesions, as well as intratumoral heterogeneity, is known to occur. Additionally, the development of acquired resistance to combination BRAF and MEK inhibitor therapy is still a formidable obstacle. Therefore, tumor heterogeneity and the development of acquired resistance have important implications for molecular testing and ultimately the treatment of patients with advanced-stage melanoma. Overall, this information may help community oncologists more accurately and effectively interpret results of diagnostic tests within the context of recent data characterizing melanoma tumor progression

Immunohistochemical analysis of chromatin remodeler DAXX in high grade urothelial carcinoma

Background/Aims: The chromatin remodeler DAXX, a predominantly nuclear protein, regulates the status of chromatin organization. The aim of this exploratory immunohistochemical study was to evaluate DAXX protein expression in high grade invasive urothelial carcinoma (UC) of the bladder as a biological regulator of aggressiveness. Methods: Quantitative analysis was made on DAXX immunostained nuclei in tissue sections from 5 cases of bladder normal urothelium (NU) and 5 cases of bladder pT1 UC. Carcinoma in situ (CIS) and high grade papillary carcinoma (HGPCa) were identified in 2 out of 5 UC cases. Results: The nuclei in UC show an open configuration of the chromatin composed of granules varying in size and distribution and a mean nuclear area 1.7 times greater than that in NU (UC: mean and SD 24.4 ± 11.4 square microns; NU: 14.8 6.5 square microns. The differences are statistically significant). 70% of the NU nuclei are immunostained, whereas 90% of UC nuclei are positive. The mean gray level value in UC, related to the intensity of nuclear immunostaining, is lower than in NU by a factor of 0.94 (UC: mean and SD 100 ± 15; NU: 106 ± 15. The differences are statistically significant). In particular, the value in the nuclei adjacent to the stroma in UC is slightly lower than in the intermediate cell layers by factor of 0.98, whereas in NU it is slightly greater by a factor 1.02 and 1.04 compared to the intermediate and superficial cell layers. The values in CIS and HGPCa are similar to those in UC. Conclusions: The quantitative immunohistochemical analysis shows an altered protein expression of chromatin remodeler DAXX in UC and in its preinvasive phases, when compared to NU. DAXX evaluation, if associated with markers related to global DNA methylation and histone acetylation, could be used in clinical practice as a marker of aggressiveness. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/139845729710237

Emerging prognostic biomarkers in testicular germ cell tumors: Looking beyond established practice

none6siTesticular germ cell tumors are unique among solid cancers. Historically, this disease was deadly if progressed beyond the stage I. The implementation of cisplatin-based chemotherapy regimens has drastically changed the clinical outcome of metastatic testicular cancer. Several biomarkers were established to refine the prognosis by International Germ Cell Collaborative Group in 1997. Among these, the most significant were primary tumor site; metastatic sites, such as non-pulmonary visceral metastases; and the amplitude of serum tumor markers α-fetoprotein, β-chorionic gonadotropin, and lactate dehydrogenase. Since then, oncology has experienced discoveries of various molecular biomarkers to further refine the prognosis and treatment of malignancies. However, the ability to predict the prognosis and treatment response in germ cell tumors did not improve for many years. Clinical trials with novel targeting agents that were conducted in refractory germ cell tumor patients have proven to have negative outcomes. With the recent advances and developments, novel biomarkers emerge in the field of germ cell tumor oncology. This review article aims to summarize the current knowledge in the research of novel prognostic biomarkers in testicular germ cell tumors.openChovanec M.; Albany C.; Mego M.; Montironi R.; Cimadamore A.; Cheng L.Chovanec, M.; Albany, C.; Mego, M.; Montironi, R.; Cimadamore, A.; Cheng, L

Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other Potential Predictive Biomarker Testing

Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different antibodies, immunohistochemical protocols, cutoffs (defining “high” vs. “low” PD-L1 expression), and scoring algorithms. The robust control of pre-analytical and analytical standards is needed to obtain high-quality PD-L1 results. To better understand the status and perspectives of biomarker-guided patient selection for anti–PD-1 and anti–PD-L1 agents in UC, three workshops were held from December 2018 to December 2019 in Italy, Malaysia, and Spain. The primary goal was to develop recommendations for best practice approaches to PD-L1 testing in UC. Recommendations pertaining to the interpretation and reporting of the results of PD-L1 assays from experienced pathologists and oncologists from around the globe are included. A test request form for pathology laboratories was developed as a critical first step for oncologists/urologists to encourage communication between clinicians and pathologists, ensuring fast and high-quality test results. In this era of personalized medicine, we briefly discuss novel biomarkers being evaluated for IO agents in UC