National Mesothelioma Virtual Bank: A standard based biospecimen and clinical data resource to enhance translational research

Background: Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods: The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result: The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion: The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers. © 2008 Amin et al; licensee BioMed Central Ltd

The development and deployment of Common Data Elements for tissue banks for translational research in cancer – An emerging standard based approach for the Mesothelioma Virtual Tissue Bank

<p>Abstract</p> <p>Background</p> <p>Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) – compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC).</p> <p>Methods</p> <p>The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML).</p> <p>Results</p> <p>Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions.</p> <p>Conclusion</p> <p>The CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained.</p

The CAP cancer protocols – a case study of caCORE based data standards implementation to integrate with the Cancer Biomedical Informatics Grid

BACKGROUND: The Cancer Biomedical Informatics Grid (caBIG™) is a network of individuals and institutions, creating a world wide web of cancer research. An important aspect of this informatics effort is the development of consistent practices for data standards development, using a multi-tier approach that facilitates semantic interoperability of systems. The semantic tiers include (1) information models, (2) common data elements, and (3) controlled terminologies and ontologies. The College of American Pathologists (CAP) cancer protocols and checklists are an important reporting standard in pathology, for which no complete electronic data standard is currently available. METHODS: In this manuscript, we provide a case study of Cancer Common Ontologic Representation Environment (caCORE) data standard implementation of the CAP cancer protocols and checklists model – an existing and complex paper based standard. We illustrate the basic principles, goals and methodology for developing caBIG™ models. RESULTS: Using this example, we describe the process required to develop the model, the technologies and data standards on which the process and models are based, and the results of the modeling effort. We address difficulties we encountered and modifications to caCORE that will address these problems. In addition, we describe four ongoing development projects that will use the emerging CAP data standards to achieve integration of tissue banking and laboratory information systems. CONCLUSION: The CAP cancer checklists can be used as the basis for an electronic data standard in pathology using the caBIG™ semantic modeling methodology

Synoptic tool for reporting of hematological and lymphoid neoplasms based on World Health Organization classification and College of American Pathologists checklist

<p>Abstract</p> <p>Background</p> <p>Synoptic reporting, either as part of the pathology report or replacing some free text component incorporates standardized data elements in the form of checklists for pathology reporting. This ensures the pathologists make note of these findings in their reports, thereby improving the quality and uniformity of information in the pathology reports.</p> <p>Methods</p> <p>The purpose of this project is to develop the entire set of elements in the synoptic templates or "worksheets" for hematologic and lymphoid neoplasms using the World Health Organization (WHO) Classification and the College of American Pathologists (CAP) Cancer Checklists. The CAP checklists' content was supplemented with the most updated classification scheme (WHO classification), specimen details, staging as well as information on various ancillary techniques such as cytochemical studies, immunophenotyping, cytogenetics including Fluorescent In-situ Hybridization (FISH) studies and genotyping. We have used a digital synoptic reporting system as part of an existing laboratory information system (LIS), CoPathPlus, from Cerner DHT, Inc. The synoptic elements are presented as discrete data points, so that a data element such as tumor type is assigned from the synoptic value dictionary under the value of tumor type, allowing the user to search for just those cases that have that value point populated.</p> <p>Results</p> <p>These synoptic worksheets are implemented for use in our LIS. The data is stored as discrete data elements appear as an accession summary within the final pathology report. In addition, the synoptic data can be exported to research databases for linking pathological details on banked tissues.</p> <p>Conclusion</p> <p>Synoptic reporting provides a structured method for entering the diagnostic as well as prognostic information for a particular pathology specimen or sample, thereby reducing transcription services and reducing specimen turnaround time. Furthermore, it provides accurate and consistent diagnostic information dictated by pathologists as a basis for appropriate therapeutic modalities. Using synoptic reports, consistent data elements with minimized typographical and transcription errors can be generated and placed in the LIS relational database, enabling quicker access to desired information and improved communication for appropriate cancer management. The templates will also eventually serve as a conduit for capturing and storing data in the virtual biorepository for translational research. Such uniformity of data lends itself to subsequent ease of data viewing and extraction, as demonstrated by rapid production of standardized, high-quality data from the hemopoietic and lymphoid neoplasm specimens.</p

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland

An Aggressive Large Epithelioid Hemangioendothelioma of the Anterior Mediastinum in a Young Woman

Hemangioendothelioma is a rare vascular tumor with involvement of the liver, brain, long bones, and lung. Among the 6 histological subtypes, epithelioid hemangioendothelioma (EHE) is the most aggressive. Its occurrence in the mediastinum is quite rare, and very few cases have been documented. The reported cases in the literature have described difficulties in the preoperative diagnosis due to the unusual histological appearance of the tumor. Immunohistochemistry remains the mainstay for a definitive diagnosis. Due to its low incidence, there is no standard treatment for mediastinal EHE, but curative resection is the preferred treatment option where possible, with chemotherapy used as an adjuvant treatment or in cases of widespread inoperable disease. The present case study describes an aggressive EHE occurring in an 18 year-old woman in the anterior mediastinum

Subfascial Endoscopic Perforator Surgery: A safe and novel minimal invasive procedure in treating varicose veins in 2nd trimester of pregnancy for below knee perforator incompetence

Aim: Aim of this study is to evaluate the results of Subfascial Endoscopic Perforator Surgery(SEPS) in treating varicose veins in 2nd trimester of pregnancy for below knee perforator incompetence. Materials and Methods: A case series was undertaken at our institute from the period January 2010 to January 2014 on 45 pregnant women. Pregnant women with failed conservative management for varicose veins were subjected to SEPS in 2nd trimester Perioperative parameters like operative time, intraoperative complications, post-operative complications, hospital stay, pain relief, ulcer healing duration and recurrence rate were studied. All the patients were reviewed and followed up for a minimum period of 3 years. Results: During the study period.total of 45 pregnant women were enrolled in the study. The median age of the patients was 26 years (range 22 years - 30 years). The mean operative time was 90±10 minutes. The post-operative hospital stay was 1-2days. There were no intraoperative complications like bleeding or gas embolism. There were no post-operative complications like seroma or abscess, port site infection, deep vein thrombosis and gas embolism. Mean healing duration of ulcers following surgery was 7-8 weeks.No patient complained of temporary or permanent paraesthesia. Every patient was subjected to follow up for a minimum period of 3 years. 5(11.1%) patients with recurrence were documented in the study. Conclusion: SEPS is a safe, cost effective and novel minimal invasive procedure in treatment of varicose veins in 2nd trimester of pregnancy for below knee perforator incompetence

Immune checkpoints and their inhibitors: Reappraisal of a novel diagnostic and therapeutic dimension in the urologic malignancies

Advances in molecular immunology have unveiled some of the complexity of the mechanisms regulating cellular immune responses and led to the successful targeting of immune checkpoints in attempts to enhance antitumor T cell responses. Surgery, chemotherapy, and radiation therapy have been the mainstay of treatment in urologic malignancies. Immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4, programmed cell death protein-1, and programmed death-ligand 1 have been shown to play central roles in evading cancer immunity. Thus these molecules have been targeted by inhibitors for the management of cancers forming the basis of immunotherapy. Immunotherapy is now among the first line therapeutic options for metastatic renal cell carcinomas. In advanced bladder cancer, immunotherapy is the standard of care in the second line and the first line for cisplatin ineligible patients. There continues to be ongoing research to identify the role if any of immunotherapy in testicular, prostatic, and penile cancers. The ideal biomarker for response to immunotherapy is still elusive. Although programmed death-ligand 1 immunohistochemical testing has been widely used across the globe as a biomarker for immunotherapy, companion diagnostic tests have inherent issues with testing and reporting and cannot have universal applicability. Additional biomarkers including, tumor mutational burden, deficient mismatch repair, high microsatellite instability, and immune gene expression profiling are being evaluated in various clinical trials. This review appraises the data of immunotherapy in the management of urologic malignancies

Primary malignant giant cell tumor of the sternum

Primary malignant giant cell tumor (PMGCT) is a diagnosis based on the presence of a high-grade sarcomatous component along with a typical benign giant cell tumor (GCT). We report the first case of PMGCT of the sternum in a 28-year-old male with painless swelling over the manubrium sterni. The differential diagnoses of PMGCT and giant cell-rich osteosarcoma were considered. Surgical resection was performed, and the reconstruction was done with a neosternum using polymethyl methacrylate and prolene mesh. At 30 months follow-up, the patient is disease-free