Vincenzo Della Mea

Digital storage of glass slides for quality assurance in histopathology and cytopathology

Proficiency testing programmes for measuring screening skills in pathology are mainly conducted using conventional glass microscope slides. However, the availability of robotic microscopes allows an entire conventional slide to be digitized. Our experiments have shown that, using a widely available robotized microscope and a PC, the image of a single field may be acquired in 2 s on average, including stage movements, autofocus and storage. Digitizing an entire slide, a fully automated procedure, takes up to 8 h. If the image of each field is compressed at an appropriate quality level (a compression ratio of, say, 35:1) it requires about 40 kByte to be stored, resulting in a total storage requirement of about 600 MByte per slide. Thus one CD-ROM can be used to store one virtual slide, as well as a self-installing program to provide a microscope simulator facility. This allows pathologists to examine the virtual case from their computer in a similar manner to looking at a glass slide on a conventional microscope. This permits a new, computer-based approach to proficiency testing in histopathology and cytopathology. Use of virtual slides should encourage the diffusion of national quality assurance programmes, which at present suffer from certain organizational and logistical limitations.

Biomarkers of lymphoma in Sjögren's syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study.

OBJECTIVES To define the biomarkers associated with lymphoproliferation in primary Sjögrens syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV). METHODS A multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkins lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions. RESULTS Six hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%). Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive. CONCLUSIONS Lymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution.

Combining dynamic and static robotic telepathology: a report on 184 consecutive cases of frozen sections, histology and cytology

The aim of this paper is to describe the experiments carried out to evaluate the diagnostic efficacy of a dynamic‐robotic telepathology system for the delivery of pathology services to distant hospitals. The system provides static/dynamic features and the remote control of a robotized microscope over 4 ISDN lines. For evaluation purposes, 184 consecutive cases of frozen sections (60), gastrointestinal pathology (64), and urinary cytology (60) have been diagnosed at a distance using the system, and the telediagnosis obtained in this way has been compared with the traditional microscopic diagnosis. Diagnostic agreement ranged from 90% in urinary cytology to 100% in frozen sections. The results obtained suggest that such a system can be considered a useful tool for supporting the pathology practice in isolated hospitals.

Internet electronic mail: a tool for low-cost telemedicine

Electronic mail, in addition to the sending of text messages, may be used to transfer multimedia and privacyenhanced messages. Email can be used for so-called store-and-forward telemedicine, which can be particularly useful for remote consultations. This paper reviews the standards used in Internet email, from communication protocols to the message formats, and pays special attention to multimedia and confidential messages; it then describes some email-based telemedicine applications. The problems of the Internet are principally the lack of any guarantee of quality of service and the low bandwidth; intranets can guarantee appropriate performance.

Measuring retrieval effectiveness: a new proposal and a first experimental validation

Most common effectiveness measures for information retrieval systems are based on the assumptions of binary relevance (either a document is relevant to a given query or it is not) and binary retrieval (either a document is retrieved or it is not). In this article, these assumptions are questioned, and a new measure named ADM (average distance measure) is proposed, discussed from a conceptual point of view, and experimentally validated on Text Retrieval Conference (TREC) data. Both conceptual analysis and experimental evidence demonstrate ADMs adequacy in measuring the effectiveness of information retrieval systems. Some potential problems about precision and recall are also highlighted and discussed.

Standardizing the use of whole slide images in digital pathology

Whole slide imaging/images (WSI) offers promising new perspectives for digital pathology. We launched an initiative in the anatomic pathology (AP) domain of integrating the healthcare enterprise (IHE) to define standards-based informatics transactions for integrating AP information and WSI. The IHE integration and content profiles developed as a result of this initiative successfully support the basic image acquisition and reporting processes in AP laboratories and provide a standard solution for sharing or exchanging structured AP reports in which observations can be explicitly bound to WSI or to regions of interest (ROI) in images.

Recent advances in standards for Collaborative Digital Anatomic Pathology.

ContextCollaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology can only be fully achieved using medical informatics standards. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive.ObjectiveTo define the best use of medical informatics standards in order to share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities.MethodsSpecific working groups dedicated to Anatomy Pathology within multiple standards organizations defined standard-based data structures for Anatomic Pathology reports and images as well as informatic transactions in order to integrate Anatomic Pathology information into the electronic healthcare enterprise.ResultsThe DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and Whole Slide Image acquisition, storage and display. The content profile “Anatomic Pathology Structured Report” (APSR) provides standard templates for structured reports in which textual observations may be bound to digital images or regions of interest. Anatomic Pathology observations are encoded using an international controlled vocabulary defined by the IHE Anatomic Pathology domain that is currently being mapped to SNOMED CT concepts.ConclusionRecent advances in standards for Collaborative Digital Anatomic Pathology are a unique opportunity to share or exchange Anatomic Pathology structured reports that are interoperable at an international level. The use of machine-readable format of APSR supports the development of decision support as well as secondary use of Anatomic Pathology information for epidemiology or clinical research.

25 years of telepathology research: a bibliometric analysis

Background The first appearance of the word “telepathology” in a scientific paper can be tracked down to 1986, in a famous editorial of Ronald Weinstein. Since that paper, research in telepathology grew up developing different subfields, including static and dynamic telepathology and more recently virtual microscopy. The present work attempts an analysis of research in telepathology, starting from the tools provided by bibliometrics.BackgroundThe first appearance of the word “telepathology” in a scientific paper can be tracked down to 1986, in a famous editorial of Ronald Weinstein. Since that paper, research in telepathology grew up developing different subfields, including static and dynamic telepathology and more recently virtual microscopy. The present work attempts an analysis of research in telepathology, starting from the tools provided by bibliometrics.MethodsA query has been developed to extract papers related to telepathology and virtual microscopy, and it has been then submitted to Pubmed by means of Entrez Utilities functions. Results obtained in XML have been processed through ad-hoc developed PHP scripts, in order to extract data on Authors, countries, and keywords.ResultsOn PubMed, 967 papers related to telepathology and virtual microscopy have been retrieved, which involved 2904 Authors; corresponding authors were from 37 countries. Of those authors, 2213 co-authored just one paper. Papers were published on 344 different journals, of which only 52 from the Pathology field. An analysis of papers per year has been also attempted, that demonstrates variable research output in time.ConclusionsFrom the proposed analysis, telepathology seems to have been consistently studied, in time, by about 400 researchers, with occasional participation of many other people. Telepathology research seems also to have varied in time, although some peaks in paper publishing are certainly related to the proceedings of the European congress on telepathology series, when they have been published on journals. However, some clear sign appears that suggests research in traditional telepathology, after a peak in 2000, showed some decline until virtual microscopy became mainstream, topic that currently pushes research again. The low number of clinical trials calls for more randomized studies in telepathology, to enable evidence-based application.

Internet agents for telemedicine services

Telemedicine can be defined as telematic support of collaboration between distant medical professionals, co-operating on shared resources of various kinds. Attention should be paid to telematics and informatics concepts, especially those oriented towards collaboration. In particular, the recent agent paradigm seems suitable for the analysis, design and development of telemedicine services because of its commitment to intercommunication and sharing of resources. The present paper is an introduction to the agent paradigm from its theoretical basis to the technological issues, and describes an agent-based approach to telemedicine, specifically applied to telepathology applications. The system is based on an agent-based model and template (JAMES) using Java, which has been used to implement a prototype multipurpose telepathology application based on a federated agency architecture.

Dynamic robotic telepathology: a preliminary evaluation on frozen sections, histology and cytology

We evaluated the diagnostic efficacy of a dynamic robotic telepathology system for the delivery of pathology services to distant hospitals. The system provided static/dynamic features and the remote control of a robotic microscope using four ISDN lines. For evaluation purposes, 184 consecutive cases were diagnosed at distance using the system. The cases were 60 frozen sections, 64 cases of gastrointestinal pathology and 60 cases of urinary cytology. The telemedicine diagnoses obtained in this way were compared with traditional microscopic diagnosis. Diagnostic agreement ranged from 90% in urinary cytology to 100% in frozen sections. The results suggest that a dynamic robotic telepathology system can be a useful tool for supporting the pathology practice of isolated hospitals.