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- Ben-Yosef, Yaara, et al.
(author)
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The HemoScreen, a novel haematology analyser for the point of care
- 2016
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In: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 69:8, s. 720-725
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: A haematology analyser, based on a new technology, is presented herein. The analyser that provides a complete blood count (CBC) and five-part differential accepts disposable cartridges containing all required reagents, making it maintenance-free and ideal for point-of-care (POC) settings. The test reproducibility and imperviousness to analytical errors are attributed to the imaging-based analysis employed. Imaging enables cell-morphology-based differentiation, which is analogous to the gold standard microscopic analysis. This article presents the HemoScreen new technology and evaluates its performance through a small-scale study conducted in its designated clinical settings.METHODS: Thirty anticoagulated whole blood samples were analysed on the HemoScreen and Sysmex XE-2100. Linear regression was performed for the methods comparison. Two samples with 15 replicates were processed for imprecision. Ease of use of the device was also considered.RESULTS: The HemoScreen demonstrated acceptable imprecision and good agreement with the Sysmex XE-2100. The white blood cells (WBCs), red blood cells (RBCs), haemoglobin (HGB), haematocrit (HCT), platelets (PLT), neutrophils, lymphocytes and eosinophils have coefficients of correlation (r) >0.97. For mean cell volume (MCV), mean cell HGB (MCH) and RBC distribution width (RDW), r values ranged from 0.92 to 0.96. For mean cell HGB concentration (MCHC) and monocytes r=0.82 was demonstrated. User-friendliness and suitability of the device for operation in the designated POC settings was also confirmed.CONCLUSIONS: The HemoScreen employs innovative technologies of viscoelastic focusing and microfluidics within a disposable cartridge for an image-based blood cell analysis. By providing accurate and repeatable CBC and five-part differential results within minutes and maintaining the simplicity of operation, the HemoScreen could have far-reaching implications for use at POC. Further extended evaluation is in progress.
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| 2. |
- Burger, Gerard, et al.
(author)
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Natural language processing in pathology: a scoping review
- 2016
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In: Journal of Clinical Pathology. - : BMJ PUBLISHING GROUP. - 0021-9746 .- 1472-4146. ; 69:11, s. 949-955
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Research review (peer-reviewed)abstract
- Background Encoded pathology data are key for medical registries and analyses, but pathology information is often expressed as free text. Objective We reviewed and assessed the use of NLP (natural language processing) for encoding pathology documents. Materials and methods Papers addressing NLP in pathology were retrieved from PubMed, Association for Computing Machinery (ACM) Digital Library and Association for Computational Linguistics (ACL) Anthology. We reviewed and summarised the study objectives; NLP methods used and their validation; software implementations; the performance on the dataset used and any reported use in practice. Results The main objectives of the 38 included papers were encoding and extraction of clinically relevant information from pathology reports. Common approaches were word/phrase matching, probabilistic machine learning and rule-based systems. Five papers (13%) compared different methods on the same dataset. Four papers did not specify the method(s) used. 18 of the 26 studies that reported F-measure, recall or precision reported values of over 0.9. Proprietary software was the most frequently mentioned category (14 studies); General Architecture for Text Engineering (GATE) was the most applied architecture overall. Practical system use was reported in four papers. Most papers used expert annotation validation. Conclusions Different methods are used in NLP research in pathology, and good performances, that is, high precision and recall, high retrieval/removal rates, are reported for all of these. Lack of validation and of shared datasets precludes performance comparison. More comparative analysis and validation are needed to provide better insight into the performance and merits of these methods.
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| 4. |
- Dessauvagie, Benjamin F., et al.
(author)
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Interobserver variation in the diagnosis of fibroepithelial lesions of the breast: a multicentre audit by digital pathology
- 2018
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In: Journal of Clinical Pathology. - : BMJ PUBLISHING GROUP. - 0021-9746 .- 1472-4146. ; 71:8, s. 672-679
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Journal article (peer-reviewed)abstract
- Aim Fibroepithelial lesions (FELs) of the breast span a morphological continuum including lesions where distinction between cellular fibroadenoma (FA) and benign phyllodes tumour (PT) is difficult. The distinction is clinically important with FAs managed conservatively while equivocal lesions and PTs are managed with surgery. We sought to audit core biopsy diagnoses of equivocal FELs by digital pathology and to investigate whether digital point counting is useful in clarifying FEL diagnoses. Method Scanned slide images from cores and subsequent excisions of 69 equivocal FELs were examined in a multicentre audit by eight pathologists to determine the agreement and accuracy of core needle biopsy (CNB) diagnoses and by digital point counting of stromal cellularity and expansion to determine if classification could be improved. Results Interobserver variation was high on CNB with a unanimous diagnosis from all pathologists in only eight cases of FA, diagnoses of both FA and PT on the same CNB in 15 and a weak mean kappa agreement between pathologists (k=0.36). Moderate agreement was observed on CNBs among breast specialists (k=0.44) and on excision samples (k=0.49). Up to 23% of lesions confidently diagnosed as FA on CNB were PT on excision and up to 30% of lesions confidently diagnosed as PT on CNB were FA on excision. Digital point counting did not aid in the classification of FELs. Conclusion Accurate and reproducible diagnosis of equivocal FELs is difficult, particularly on CNB, resulting in poor interobserver agreement and suboptimal accuracy. Given the diagnostic difficulty, and surgical implications, equivocal FELs should be reported in consultation with experienced breast pathologists as a small number of benign FAs can be selected out from equivocal lesions.
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| 5. |
- Gulyas, Miklos, et al.
(author)
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Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology
- 2019
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In: Journal of Clinical Pathology. - : BMJ PUBLISHING GROUP. - 0021-9746 .- 1472-4146. ; 72:8, s. 529-535
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Journal article (peer-reviewed)abstract
- Aims In order to improve diagnostics in pleural effusions, additional value of effusion cholesterol, carcinoembryonic antigen (CEA) and syndecan-2 assays to cytology was studied. Methods Biomarkers were measured in effusion supernatants from 247 patients, of whom 126 had malignant pleural involvement, and their additional diagnostic efficacy to cytology was assessed. Results Syndecan-2 measurement, although gave detectable concentrations in all effusions with highest median value in mesotheliomas, was non-discriminative between different pathological conditions. CEA concentrations exceeding 5 ng/mL cut-off point indicated carcinomas, regardless of pleural involvement, which gave a sensitivity of 62% and specificity of 100% for carcinoma. Cholesterol concentration over 1.21 mmol/L cut-off value indicated neoplastic pleural involvement with 99% sensitivity and 'merely' 69% specificity, the latter mainly due to raised levels being associated also with benign inflammatory effusions. Combined CEA and cholesterol determinations increased the sensitivity for diagnosing carcinomatosis from 70% with cytology alone to 84% and established the correct diagnosis in 16 of 31 carcinomatosis cases with inconclusive cytology. Cholesterol measurement alone, with elevated level, in combination with absence of substantial number of inflammatory cells in effusion sediment proved to be a magnificent marker for neoplastic pleural involvement with 99% efficacy, and recognised all 36 such cases with inconclusive cytology. Conclusions Simultaneous measurement of CEA and cholesterol concentrations in effusion, or at least cholesterol alone, in combination with non-inflammatory fluid cytology, provides additional specific information about neoplastic pleural involvement, and can therefore be used as an adjunct to cytology, above all, in inconclusive cases.
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| 7. |
- Hedner, Charlotta, et al.
(author)
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Expression and prognostic significance of human epidermal growth factor receptors 1, 2 and 3 in oesophageal and gastric adenocarcinomas preneoadjuvant and postneoadjuvant treatment
- 2018
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In: Journal of Clinical Pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 71:5, s. 451-462
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Journal article (peer-reviewed)abstract
- AIMS: Neoadjuvant treatment has now become the standard of care for oesophageal and gastric cancer. The aim of this study was to investigate the influence of neoadjuvant therapy on the expression of human epidermal growth factor receptor 1 (HER1/EGFR), HER2 and HER3, in oesophageal and gastric adenocarcinoma.METHODS: Immunohistochemical expression of EGFR, HER2 and HER3 was examined and compared in pretreatment biopsies, post-treatment surgical resection specimens and metastases in a retrospective cohort of 166 patients with adenocarcinoma of the oesophagus or stomach. The relationship between expression of the investigative markers and histopathological response to neoadjuvant treatment, overall survival (OS) and recurrence free survival (RFS) was analysed.RESULTS: Conversion of protein expression between pretreatment biopsy and post-treatment surgical resection was seen in 4.6% of the cases for EGFR, 5.9% for HER2% and 19.4% for HER3. Histopathological response to neoadjuvant treatment was significantly and stepwise associated with OS and RFS . High HER3 protein expression in post-treatment surgical resection specimens was significantly associated with a prolonged OS in univariable analysis (HR=0.39; 95% CI 0.17 to 0.93), but did not remain significant in multivariable analysis. Expression of EGFR and HER2 in post-treatment surgical resection specimens was not prognostic. No correlation between pretreatment HER-protein expression and histopathological response was seen.CONCLUSIONS: The results from this study underscore the need for further studies on the influence of neoadjuvant treatment on biomarker expression, as this may influence treatment strategy as well as prognosis. Histopathological response is validated as a useful prognostic factor.
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| 8. |
- Lin, YB, et al.
(author)
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Telomerase promoter mutations and copy number alterations in solitary fibrous tumours
- 2018
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In: Journal of clinical pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 71:9, s. 832-839
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Journal article (peer-reviewed)abstract
- Solitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by the NAB2–STAT6 fusion gene. Activating mutations in the telomerase reverse transcriptase (hTERT) gene promoter has been reported to associate with adverse patient outcome in SFTs.MethodsWe analysed the hTERT gene for promoter mutations and copy number alterations in 43 primary extrameningeal SFTs (9 malignant and 34 benign tumours according to WHO 2013 criteria), six local recurrences and three metastatic lesions.ResultsActivating −124 C>T (n=12) or −148 C>T (n=2) mutations were found in 33% of the tumours and associated with older age (P=0.006), necrosis (P=0.009), higher mitotic rate (P=0.003), nuclear atypia (P=0.002), malignant histological diagnosis (P=0.04) and worse progression-free survival (P=0.023). We also observed frequent (24%) hTERT promoter mutations in histologically benign tumours without metastasis (mean follow-up >9 years), and in 14%–18% of low-risk SFTs as determined by three risk-stratification models. Mutations were seen in 2/6 metastatic tumours and metastatic lesions. hTERT copy number gain was seen in 11/28 hTERT promoter wild-type cases.ConclusionsActivating hTERT promoter mutations associate with aggressive histopathological features, indicating a role in tumour progression. Given the comparatively high prevalence of hTERT promoter mutations in low-risk and non-metastasising lesions, further studies are required to clarify the prognostic value of hTERT promoter analysis before implementing the analysis in clinical diagnostics.
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| 9. |
- Linder, Nina, et al.
(author)
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Deep learning for detecting tumour-infiltrating lymphocytes in testicular germ cell tumours
- 2019
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In: Journal of Clinical Pathology. - : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 72:2, s. 157-164
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Journal article (peer-reviewed)abstract
- AIMS: To evaluate if a deep learning algorithm can be trained to identify tumour-infiltrating lymphocytes (TILs) in tissue samples of testicular germ cell tumours and to assess whether the TIL counts correlate with relapse status of the patient.METHODS: TILs were manually annotated in 259 tumour regions from 28 whole-slide images (WSIs) of H&E-stained tissue samples. A deep learning algorithm was trained on half of the regions and tested on the other half. The algorithm was further applied to larger areas of tumour WSIs from 89 patients and correlated with clinicopathological data.RESULTS: A correlation coefficient of 0.89 was achieved when comparing the algorithm with the manual TIL count in the test set of images in which TILs were present (n=47). In the WSI regions from the 89 patient samples, the median TIL density was 1009/mm2. In seminomas, none of the relapsed patients belonged to the highest TIL density tertile (>2011/mm2). TIL quantifications performed visually by three pathologists on the same tumours were not significantly associated with outcome. The average interobserver agreement between the pathologists when assigning a patient into TIL tertiles was 0.32 (Kappa test) compared with 0.35 between the algorithm and the experts, respectively. A higher TIL density was associated with a lower clinical tumour stage, seminoma histology and lack of lymphovascular invasion.CONCLUSIONS: Deep learning-based image analysis can be used for detecting TILs in testicular germ cell cancer more objectively and it has potential for use as a prognostic marker for disease relapse.
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| 10. |
- Nyström, H., et al.
(author)
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Hypoxia-inducible factor 1a predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall
- 2017
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In: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 70:10, s. 879-885
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Journal article (peer-reviewed)abstract
- Background and aim Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and pleomorphic undifferentiated sarcoma. Method We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)a using immunohistochemical staining and assessed microvessel density using CD31 in 73 highgrade leiomyosarcomas and undifferentiated pleomorphic sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival. Results Expression of HIF-1a was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither expression of the stromal markers CD163, CD16 and CSF-1 nor microvessel density was prognostically relevant in this series. Conclusions There is increasing evidence for the prognostic role of hypoxia in high-grade soft tissue sarcoma, and these data suggest that HIF-1a expression represents a candidate prognostic biomarker for clinical application in high-grade leiomyosarcoma and undifferentiated pleomorphic sarcoma.
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