Telepathology in Norway: A Review Article

Introduction: We reviewed a development and status of telepathology in Norway. Methods: The article is based on search in PubMed including “digital pathology” and “Norway”, “digital pathology” or “telepathology” and “Norway”, and “telepathology” and “Norway” as search terms. Results: Our review of selected 42 articles, published in peer reviewed journals, showed a steady development of telepathology and digital pathology in Norway contributing to widely accepted general applications and routine diagnostic uses including digital image analysis. Conclusions: The organization and execution of pathology services in histology, cytology and autopsy including teaching, research, and interdepartmental collaboration have been all improved by implementation of telepathology and digital pathology in Norway. Abbreviations: NST: Norwegian Centre for Telemedicine; OSODs: Original Second Opinion Diagnoses;


Introduction
Telepathology, also known today as digital pathology, whole slide imaging and virtual microscopy, stands for diagnostics, education and research using digital images of microscopic slides.
Since the pioneering work of Weinstein RS, telepathology has become an integral part of a modern pathology diagnostics. In addition to better ergonomics, instant access to slides and remote diagnostics, considerable technological advances contributed to the growing appeal of telepathology through years. Those evolved from still image diagnostics, through robotic microscopy and hybrid systems to novel scanning techniques [1][2][3]. Nordrum I and Eide TJ introduced telepathology in Norway in the late 1980 [4][5][6][7][8][9]. Multiple Norwegian pathology departments have been since implementing telepathology solutions in diverse clinical settings and degrees [10][11][12][13][14][15][16][17]. The Norwegian Centre for Telemedicine (NST) has made a tremendous contribution to the development and implementation of telemedicine and health services in Norway, including telepathology, over the past three decades. It has served as a WHO Collaboration Center for telemedicine since 2002. Since its introduction in 1996, an official telemedicine fee schedule has made telemedical services reimbursable by national health insurers for the first time in the world [18]. In this article, we reviewed development and status of telepathology in Norway, based of works published in peer reviewed journals. The list of reviewed articles in chronological order is shown in (Table 1).

Methods
We based our review on the search conducted in PubMed.
Search terms included "digital pathology" and "Norway", "digital pathology" or "telepathology" and "Norway", and "telepathology" and "Norway". We have used a combination of "MeSH" and "All field" options to conduct the search. Inclusion criteria were all papers published to the present day. We have found altogether 211 publications in all three searches, cross-matched them, and ended up with 41 publications fulfilling our subject criteria.

General Considerations
The term "telepathology" has been used in 1986 for the first time.
Initially, dynamic (real time) and static image (store-and-forward) telepathology were the first two competing modalities. The hybrid imaging system, which combined these two primary pathology imaging modalities into a single multi-modality pathology imaging system was established by Norwegian laboratory in 1989. Similar hybrid systems followed in other countries as well. It is important to emphasize that hybrid telepathology systems were the starting point for the first genuinely sustainable telepathology services.
Since then, astounding technical progress resulted in development "virtual microscopy" telepathology (also called "whole slide image" telepathology or "WSI" telepathology of digital pathology increasing number of health-care professionals exposed to and using telemedicine in the routine fashion, continued sustenance of the Norwegian health authorities, a national center guiding telemedicine research, no licensing barriers within the country, nationwide ISDN and reimbursement for telemedicine services, the future of telemedicine in Norway looked promising at the time [10].
The investigation by Aas IH, which was part of a larger study, and detailed information and discussions needed to be produced by users in order to attract further users, in expectation that the network was to be run by itself.
As this did not work, the study suggested that an open discussion among pathologists would be useful to explore and highlight emerging dilemmas [21]. The Northern Norway Regional Health Authority requested the evaluation of telemedicine services The first priority topics were teleradiology, digitalization of patient records and education. The second priority topics were teledialysis, pre-hospital thrombolysis, telepsychiatry and teledermatology.
The third priority topics were pediatrics, district medical centers, tele-ophthalmology, and tele-otorhinolaryngology. No priority was designed for the projects in cardiology, endocrinology, geriatrics, gynecology/obstetrics, pathology, and nursing/care. in the region [11].
Pathologists in Telemark have used the telepathology for teaching cytopathology to cytoscreeners and pathology assistants.
One was local and the other remote, in the refional hospital from their experience at the time, it was more convenient and cheaper to use internet-based than Path Sight telepathology [15]. Knudsen Two pathologists made diagnosis first on the still images (phase 1) followed by glass slides (phase 2). Both diagnoses were compared with the original second opinion diagnoses (OSODs).
The same diagnostic was made on both still images and glass slides. There were 29 cases with the diagnosis discordant with the OSOD. Incorrect benign diagnoses were recorded in three cases. including both local and regional education and cooperation [17].

Digital Image Analysis
Skaland, et al. [31] correlated modified FISH scores with HER2 3+ score, agreed between pathologists, and digital image analysis The prognostic threshold of PHH3 was the strongest prognostic factor. It has been shown as a robust, highly reproducible, prognostic over the thresholds around 13, and is the overall strongest prognostic factor amongst studied for patients with invasive, lymph node negative, and under 71 years old [33]. Immune modulating molecules cyclooxygenase-2 (COX-2), transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) regulate advancement of cancer cells, with conflicting data on their exact risk of the disease specific death. This could also effectively stratify a subpopulation of patients with a characteristic risk of recurrence and assist the choice of adjuvant therapy for these patients [43].
The results were collated with a standard IHC performed on the same tissue. The methods were comparable. Although DIA refined levels of differentiation in cases with high and low reactivity, there were challenges in DIA interpretation of membrane reactions, more consistently evaluated on the microscope. Combined use of DIA and mIHC assured quantification rates of marker's expression.
The result suggested a strong negative correlation between CDX2 and SOX2. Prognostication levels of CDX2 were confirmed, however, visualization and detection of associations between pathology and biology of tumors. This method showed as a potential novel way to regiment CDX2 detection [44].

Conclusion
Since the pioneering work of Nordrum and Eide, telepathology in Norway has come a long way in the last 30 years, improving routine diagnostics, education, and consultations. There is ongoing national digital pathology project, which has been driven by continuous increase in workload and shortages of pathologists.
Main objectives with the project are to improve patient care through shorter turnaround time, faster and more precise diagnostics, increase patient safety, increase utilization of the existing overall expertise and capacity of the pathology departments, strengthen education, and maintain recruitment to the pathology profession.
Its concept was introduced in 2016 and business plan approved in 2017. The project has entered its implementation phase in 2018.
The investment is expected to be repaid by the end of 2022. All four regional health authorities are expected to become fully digitalized by 2025 (https://ehelse.no/prosjekt/digital-patologi).