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Cancers Apr 2021In contrast to the decline in incidence and mortality of most other cancers, these rates are rising for endometrial cancer. Black women with endometrial cancer have... (Review)
Review
In contrast to the decline in incidence and mortality of most other cancers, these rates are rising for endometrial cancer. Black women with endometrial cancer have earlier diagnosis, more aggressive histology, advanced stage and worse outcomes compared with their White counterparts. Socioeconomic status, a higher incidence of aggressive histology, and comorbid conditions are known factors leading to racial disparity in patients with endometrial cancer; nevertheless, they do not account for the entire racial disparity; which emphasizes the roles of molecular, histopathological and genetic factors. We performed a comprehensive review of all published scientific literature up to January 2021 reporting histopathologic, genetic and molecular factors associated with racial disparities in patients with endometrial cancer. The interactions and pathways of molecules reported to have significant differential expression in endometrial cancers from Black and White patients were identified with Ingenuity Pathway Analysis. The majority of studies compared Black and White patients; however, limited data are available for other racial and ethnic groups. Reported differences that could account for the worse survival of Black endometrial cancer patients include more aggressive histopathologies and molecular alterations, including upregulation of molecules driving cell cycle progression, and p53 and HER2/NEU signaling. Several of these molecules are targeted by existing pharmaceuticals. These findings encourage further study and the development of race-specific treatment strategies.
PubMed: 33920951
DOI: 10.3390/cancers13081900 -
Journal of Surgical Oncology Oct 2022Resulting from 50 years of innovation, operations for pancreatic neoplasms can now be performed safely, albeit with significant but manageable morbidity. Molecular...
Resulting from 50 years of innovation, operations for pancreatic neoplasms can now be performed safely, albeit with significant but manageable morbidity. Molecular diagnosis has allowed for the identification of multiple distinct histopathologies with variable natural histories. Observation is now a strategy for selected indolent cysts and some neuroendocrine neoplasms. For ductal pancreatic adenocarcinoma, a long-term cure remains elusive and will require more than surgical resection for meaningful progress.
Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; Humans; Neuroendocrine Tumors; Pancreatic Neoplasms
PubMed: 36087087
DOI: 10.1002/jso.27030 -
Ocular Immunology and Inflammation 2022To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two...
PURPOSE
To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two patients with unique clinical courses, cytopathologic findings, and immune response.
METHODS
A retrospective review of patients with ARN who developed retinal detachment (RD) and underwent PPV from 22011 to 2019 at the Emory Eye Center was performed to assess cytopathology findings of vitreous biopsy samples. Patient demographics and laboratory testing including aqueous humor PCR for viral pathogens were recorded. Additional clinical details abstracted included intravitreal injections, surgical procedures, and vitreous cytopathological reports including immunohistochemistry findings.
RESULTS
Fourteen eyes of 12 patients with RD were reviewed. Ten eyes showed HSV DNA (71%) and 4 demonstrated VZV DNA (29%). All eyes received intravitreal antivirals (i.e. ganciclovir or foscarnet) with a median of 8.5 intravitreal injections per eye. Diagnoses prompting PPV included tractional RD in 14 eyes (100%), rhegmatogenous RD in 8 eyes (57%), vitreous hemorrhage in 4 eyes (29%) and vitreous opacity in 4 (29%). Ophthalmic pathology reports showed lymphocyte populations in 10 eyes (71%) with a CD3 + T-cell predominance in two patients where immunohistochemistry of CD3+ and CD20+ for T- and B-cell populations was performed. Observed immune cell populations included macrophages or histiocytes (11 eyes, 79%) and polymorphonuclear cells in 4 eyes (29%). Initial median VA was 2.5 (IQR 2.0-3.0) and improved to 2.0 (IQR 1.48-3.00, = .48) at 6-months and 1.8 (IQR 1.2-3.0, = .45) at 12 months follow-up.
CONCLUSIONS
Our cohort of ARN patients undergoing PPV show a spectrum of immunologic findings with the majority demonstrating a lymphocytic response. Histiocytes, macrophages, and PMNs were also observed. Cytopathologic and immunologic studies suggest that both innate and adaptive immunity are responsible for the clinical disease findings observed in ARN. The variability of the response to treatment in patients with ARN may reflect patient-to-patient differences in their antigen-specific immune response. Understanding the immunologic response associated with ARN may provide valuable information regarding the dosing and timing of treatment.
Topics: Humans; Retinal Necrosis Syndrome, Acute; Cytology
PubMed: 34242097
DOI: 10.1080/09273948.2021.1922926 -
Internal Medicine (Tokyo, Japan) Jan 2023TAFRO syndrome was first described in 2010, standing for thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Because the lymph node histopathology of...
TAFRO syndrome was first described in 2010, standing for thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Because the lymph node histopathology of TAFRO syndrome mimics idiopathic multicentric Castleman disease (iMCD), some researchers consider TAFRO syndrome to be a subtype of iMCD. However, the clinical features of TAFRO syndrome considerably differ from those of iMCD without TAFRO. The clinical features of patients with TAFRO syndrome with or without iMCD-histopathology are similar, and these patients require an accurate diagnosis and urgent treatment. Although a histological diagnosis, including a differential diagnosis, is important, lymph node involvement in patients with TAFRO syndrome is usually modest or sometimes absent. Furthermore, a bleeding tendency due to thrombocytopenia and severe anasarca hampers performing a biopsy. Nonetheless, patients with various other disorders may manifest TAFRO syndrome-like symptoms, making the differential diagnosis in borderline cases difficult. Therefore, the establishment of precise and specific biomarkers is important.
Topics: Humans; Castleman Disease; Lymph Nodes; Thrombocytopenia; Edema
PubMed: 35598998
DOI: 10.2169/internalmedicine.9622-22 -
Archives of Pathology & Laboratory... Jan 2022The presence of allogeneic contamination impacts clinical reporting in cancer next-generation sequencing specimens. Although consensus guidelines recommend the...
CONTEXT.—
The presence of allogeneic contamination impacts clinical reporting in cancer next-generation sequencing specimens. Although consensus guidelines recommend the identification of contaminating DNA as a part of quality control, implementation of contamination assessment methods in clinical molecular diagnostic laboratories has not been reported in the literature.
OBJECTIVE.—
To develop and implement a method to assess allogeneic contamination in clinical cancer next-generation sequencing specimens.
DESIGN.—
We describe a method to detect contamination based on the evaluation of single-nucleotide polymorphic sites from tumor-only specimens. We validate this method and apply it to a large cohort of cancer sequencing specimens.
RESULTS.—
Identification of specimen contamination was validated via in silico and in vitro mixtures, and reference range and reproducibility were established in a panel of normal specimens. The algorithm accurately detects an episode of systemic contamination due to reagent impurity. We prospectively applied this algorithm across 7571 clinical cancer specimens from a targeted next-generation sequencing panel, in which 262 specimens (3.5%) were predicted to be affected by greater than 5% contamination.
CONCLUSIONS.—
Allogeneic contamination can be inferred from intrinsic cancer next-generation sequencing data without paired normal sequencing. The adoption of this approach can be useful as a quality control measure for laboratories performing clinical next-generation sequencing.
Topics: High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Pathology, Molecular; Polymorphism, Single Nucleotide; Reproducibility of Results
PubMed: 34015814
DOI: 10.5858/arpa.2020-0679-OA -
Molecular Biology Reports Oct 2022During the course of 2020, the outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread rapidly across the world. Clinical diagnostic testing for... (Review)
Review
During the course of 2020, the outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread rapidly across the world. Clinical diagnostic testing for SARS-Cov-2 infection has relied on the real-time Reverse Transcriptase Polymerase Chain Reaction and is considered the gold standard assay. Commercial vendors and laboratories quickly mobilised to develop diagnostic tests to detect the novel coronavirus, which was fundamentally important in the pandemic response. These SARS-Cov-2 assays were developed in line with the Food Drug Administration-Emergency Use Authorization guidance. Although new tests are continuously being developed, information about SARS-CoV-2 diagnostic molecular test accuracy has been limited and at times controversial. Therefore, the analytical and clinical performance of SARS-CoV-2 test kits should be carefully considered by the appropriate regulatory authorities and evaluated by independent laboratory validation. This would provide improved end-user confidence in selecting the most reliable and accurate diagnostic test. Moreover, it is unclear whether some of these rapidly developed tests have been subjected to rigorous quality control and assurance required under good manufacturing practice. Variable target gene regions selected for currently available tests, potential mutation in target gene regions, non-standardized pre-analytic phase, a lack of manufacturer independent validation data all create difficulties in selecting tests appropriate for different countries and laboratories. Here we provide information on test criteria which are important in the assessment and selection of SARS-CoV-2 molecular diagnostic tests and outline the potential issues associated with a proportion of the tests on the market.
Topics: COVID-19; COVID-19 Testing; Humans; Pandemics; Pathology, Molecular; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35441938
DOI: 10.1007/s11033-022-07455-5 -
The Journal of Molecular Diagnostics :... May 2022Systematic implementation of bioinformatics resources for next generation sequencing (NGS)-based clinical testing is an arduous undertaking. One of the key challenges... (Review)
Review
Systematic implementation of bioinformatics resources for next generation sequencing (NGS)-based clinical testing is an arduous undertaking. One of the key challenges involves developing an ecosystem of information technology infrastructure for enabling scalable and reproducible bioinformatics services that is resilient and secure for handling genetic and protected health information, often embedded in an existing non-bioinformatics-oriented infrastructure. Container technology provides an ideal and infrastructure-agnostic solution for molecular laboratories developing and using bioinformatics pipelines, whether on-premise or using the cloud. A container is a technology that provides a consistent computational environment and enables reproducibility, scalability, and security when developing NGS bioinformatics analysis pipelines. Containers can increase the bioinformatics team's productivity by automating and simplifying the maintenance of complex bioinformatics resources, as well as facilitate validation, version control, and documentation necessary for clinical laboratory regulatory compliance. Although there is increasing popularity in adopting containers for developing NGS bioinformatics pipelines, there is wide variability and inconsistency in the usage of containers that may result in suboptimal performance and potentially compromise the security and privacy of protected health information. In this article, the authors highlight the current state and provide best or recommended practices for building, using containers in NGS bioinformatics solutions in a clinical setting with focus on scalability, optimization, maintainability, and data security.
Topics: Computational Biology; Ecosystem; High-Throughput Nucleotide Sequencing; Humans; Pathology, Molecular; Reproducibility of Results; Software
PubMed: 35189355
DOI: 10.1016/j.jmoldx.2022.01.006 -
The American Journal of Pathology May 2021Correct use of statistical methods is important to ensure the reliability and value of the published experimental pathology literature. Considering increasing interest... (Review)
Review
Correct use of statistical methods is important to ensure the reliability and value of the published experimental pathology literature. Considering increasing interest in the quality of statistical reporting in pathology, the statistical methods used in 10 recent issues of the American Journal of Pathology were reviewed. The statistical tests performed in the articles were summarized, with attention to their implications for contemporary pathology research and practice. Among the 195 articles identified, 93% reported using one or more statistical tests. Retrospective statistical review of the articles revealed several key findings. First, tests for normality were infrequently reported, and parametric hypothesis tests were overutilized. Second, studies reporting multisample hypothesis tests (eg, analysis of variance) infrequently performed post hoc tests to explore differences between study groups. Third, correlation, regression, and survival analysis techniques were underutilized. On the basis of these findings, a primer on relevant statistical concepts and tests is presented, including issues related to optimal study design, descriptive and comparative statistics, and regression, correlation, survival, and genetic data analysis.
Topics: Humans; Pathology; Periodicals as Topic; Reproducibility of Results; Research Design; Retrospective Studies; Statistics as Topic
PubMed: 33652018
DOI: 10.1016/j.ajpath.2021.02.009 -
Journal of Clinical Pathology Oct 2019Rapid procurement of a wide variety of metastatic and primary cancers and normal tissues after death through rapid autopsy opens largely unexplored avenues in cancer...
AIMS
Rapid procurement of a wide variety of metastatic and primary cancers and normal tissues after death through rapid autopsy opens largely unexplored avenues in cancer research. We describe a high-volume rapid research autopsy programme at a large academic medical centre.
METHODS
Advanced-stage cancer patients, most commonly inpatients in palliative care facilities, were approached to participate in a cancer research autopsy programme with the goal of acquiring multidimensionally annotated tissue for cancer research. On death of an enrolled patient, a predetermined notification plan was enacted, with the medical oncologist/clinical research coordinator informing a team of pathologists, researchers and allied staff. Quality assurance metrics were measured. Thereafter, tissues were annotated in a tissue bioinformatics database and linked to electronic patient records. All banked tissues were reviewed for tumour integrity, including DNA and RNA quality.
RESULTS
Over 100 rapid research autopsies from diverse cancer sites were performed, and specimens were procured and annotated with detailed clinical information, including treatment and response. Tissues were successfully enabling studies of tumour immunology, xenografts, genomics and proteomics.
CONCLUSIONS
Large-scale rapid procurement and biobanking of cancer tissues from a rapid autopsy programme is feasible. Multidisciplinary integration between health and administrative staff from medical oncology, palliative care, pathology and biospecimen sciences is critical for the success of this challenging endeavour.
Topics: Adult; Aged; Aged, 80 and over; Autopsy; Female; Genomics; Humans; Male; Medical Oncology; Middle Aged; Neoplasms; Palliative Care; Pathology, Surgical; Proteomics; Tissue Banks; Young Adult
PubMed: 31262953
DOI: 10.1136/jclinpath-2019-205874 -
Scientific Reports Sep 2022To investigate the value of the radiomic models for differentiating parasellar cavernous hemangiomas from meningiomas and to compare the classification performance with...
To investigate the value of the radiomic models for differentiating parasellar cavernous hemangiomas from meningiomas and to compare the classification performance with different MR sequences and classifiers. A total of 96 patients with parasellar tumors (40 cavernous hemangiomas and 56 meningiomas) were enrolled in this retrospective multiple-center study. Univariate and multivariate analyses were performed to identify the clinical factors and semantic features of MRI scans. Radiomics features were extracted from five MRI sequences using radiomics software. Three feature selection methods and six classifiers were evaluated in the training cohort to construct favorable radiomic machine-learning classifiers. The performance of different classifiers was evaluated using the AUC and compared to neuroradiologists. The detection rates of TWI, TWI, and CE-TWI for parasellar cavernous hemangiomas and meningiomas were approximately 100%. In contrast, the ADC maps had the detection rate of 18/22 and 19/25, respectively, (AUC, 0.881) with 2.25 cm as the critical value diameter. Radiomics models with the SVM and KNN classifiers based on TWI and ADC maps had favorable predictive performances (AUC > 0.90 and F-score value > 0.80). These models outperformed MRI model (AUC 0.805) and neuroradiologists (AUC, 0.756 and 0.545, respectively). Radiomic models based on TWI and ADC and combined with SVM and KNN classifiers have the potential to be a viable method for differentiating parasellar hemangiomas from meningiomas. TWI is more universally applicable than ADC values due to its higher detection rate for parasellar tumors.
Topics: Hemangioma, Cavernous; Humans; Machine Learning; Meningeal Neoplasms; Meningioma; Neuroblastoma; Retrospective Studies
PubMed: 36109577
DOI: 10.1038/s41598-022-19770-9