Biobanking for better healthcare

Translational cancer research is highly dependent of large series of cases including high quality samples and their associated data. Comprehensive Cancer Centers should be involved in networks to enable large‐scale multi‐center research projects between the centers [Ringborg, U., de Valeriola, D., van Harten, W., Llombart‐Bosch, A., Lombardo, C., Nilsson, K., Philip, T., Pierotti, M.A., Riegman, P., Saghatchian, M., Storme, G., Tursz, T., Verellen, D, 2008. Improvement of European translational cancer research. Collaboration between comprehensive cancer centers. Tumori 94, 143–146.]. Combating cancer knows many frontiers. Research is needed for prevention as well as better care for those who have acquired the disease. This implies that human samples for cancer research need to be sourced from distinct forms of biobanking. An easier access to these samples for the scientific community is considered as the main bottleneck for research for health, and biobanks are the most adequate site to try to resolve this issue [Ozols, R.F., Herbst, R.S., Colson, Y.L., Gralow, J., Bonner, J., Curran Jr., W.J., Eisenberg, B.L., Ganz, P.A., Kramer, B.S., Kris, M.G., Markman, M., Mayer, R.J., Raghavan, D., Reaman, G.H., Sawaya, R., Schilsky, R.L., Schuchter, L.M., Sweetenham, J.W., Vahdat, L.T., Winn, R.J., and the American Society of Clinical Oncology, 2007. Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening: a report from the American Society of Clinical Oncology. J. Clin. Oncol. 25, 146–162.].However, biobanks should not be considered a static activity. On the contrary, biobanking is a young discipline [Morente, M.M., Fernandez, P.L., de Alava, E. Biobanking: old activity or young discipline? Semin. Diagn. Pathol., in press.], which need continuously evolve according to the permanent development of new techniques and new scientific goals. To accomplish current requirements of the scientific community biobanks need to face some essential challenges including an appropriate design, harmonized and more suitable procedures, and sustainability, all of them in the framework of their ethic, legal and social dimensions.This review therefore presents an overview on these issues, based on the works and discussions of the Marble Arch International Working Group on Biobanking for Biomedical Research, integrated by experts in biobanking from five continents.     

Systems pathology: a critical review

The technological advances of the last twenty years together with the dramatic increase in computational power have injected new life into systems-level thinking in Medicine. This review emphasizes the close relationship of Systems Pathology to Systems Biology and delineates the differences between Systems Pathology and Clinical Systems Pathology. It also suggests an algorithm to support the application of systems-level thinking to clinical research, proposes applying systems-level thinking to the health care systems and forecasts an acceleration of preventive medicine as a result of the coupling of personal genomics with systems pathology.     

Molecular pathology – The value of an integrative approach

Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a proper model or trained pathologists to support the diagnostic and research missions makes MP a rare commodity overall.Here we analyse the scientific and technology areas, in research and diagnostics, which are encompassed by MP of solid tumours; we highlight the broad overlap of technologies and analytical capabilities in tissue research and diagnostics; and we describe an integrated model that rationalizes technical know‐how and pathology talent for both. The model is based on a single, accredited laboratory providing a single standard of high‐quality for biomarker discovery, biomarker validation and molecular diagnostics.     

基于深度学习的人工智能在数字病理学中的进展

全切片数字化图像扫描技术的进步促成了数字病理学的诞生。随着存储技术的提高和互联网技术与计算机技术的迅速发展,深度学习的方法被广泛应用于病理学图像的分析中,其目标是化解病理学图像冗余复杂的信息导致病理学医师诊断和分析困难的问题,减轻病理学医师日常繁琐的分析工作,并提高分析结果的准确度。回顾分析常用于病理学分析的深度学习方法,介绍深度学习在病理学分析中各领域的应用,并讨论深度学习在病理学分析中的挑战和机遇。     

Molecular pathology

Molecular pathology as applied to neoplasia is a rapidly expanding component of the discipline of pathology that uses molecular biology tools in addition to conventional morphologic, immunohistochemical and chemical analyses of abnormalities in tissues and cells to understand the etiology and pathogenesis of tumors, establish their diagnosis, and contribute to prognostication and therapeutic decisions for cancer patient care. Biomarkers are a fundamental component of personalized cancer care, and the discipline of molecular pathology therefore contributes throughout the continuum from biomarker research to use in standard-of-care personalized cancer therapy. This brief review addresses some of the specific roles of molecular pathology in that continuum.     

Redefining shared decision-making in the digital era

Perioperative shared decision-making can be improved through the development of novel patient-centered outcome measures made possible by digital phenotyping—“the moment-by-moment quantification of individual-level human phenotype in situ using data from personal digital devices, in particular smartphones.” This Short Report presents data from a patient with breast cancer that illustrates the opportunities of digital phenotyping to better inform patient quality of life while also discussing the challenges to its adoption. With time, effort, and physician engagement, digital phenotyping can help surgeons better understand the patient experience in the postoperative period and in turn, help them provide care that maximizes patient quality of life.     

PICan: An integromics framework for dynamic cancer biomarker discovery

Modern cancer research on prognostic and predictive biomarkers demands the integration of established and emerging high‐throughput technologies. However, these data are meaningless unless carefully integrated with patient clinical outcome and epidemiological information. Integrated datasets hold the key to discovering new biomarkers and therapeutic targets in cancer. We have developed a novel approach and set of methods for integrating and interrogating phenomic, genomic and clinical data sets to facilitate cancer biomarker discovery and patient stratification. Applied to a known paradigm, the biological and clinical relevance of TP53, PICan was able to recapitulate the known biomarker status and prognostic significance at a DNA, RNA and protein levels.     

Optimal breast cancer pathology manifesto

This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014.It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus.It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community – pathologists, oncologists, patient advocates, health administrators and policymakers – to check that services are available that serve the needs of patients in a high quality, timely way.     

Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery

BACKGROUNDGastric cancer (GC) is a highly heterogeneous disease, and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups. However, the costs and technical complexity of molecular methodologies remains an obstacle to its adoption, and their clinical significance by other approaches needs further evidence.AIMTo evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry (IHC) and in situ hybridization (ISH).METHODSWe retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent. Microsatellite instability (MSI) status, E-cadherin, and p53 expression were analyzed by IHC, and Epstein-Barr virus (EBV) by ISH. Tissue microarrays were constructed for analysis. Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas (TCGA) Research Network Group and Asian Cancer Research Group (ACRG) classification systems.RESULTSA total of 287 GC patients were included. Based on IHC and ISH analysis, five profiles were defined as follows: E-cadherin aberrant (9.1%), MSI (20.9%), p53 aberrant (36.6%), EBV positivity (10.5%), and p53 normal (31%), which corresponded to tumors that showed no alteration in another profile. A flowchart according to the TCGA and ACRG classifications were used to define the subtypes, where clinical and pathological characteristics associated with GC subtypes were evidenced. Proximal location (P < 0.001), total gastrectomy (P = 0.001), and intense inflammatory infiltrate (P < 0.001) were characteristics related to EBV subtype. MSI subtype was predominantly associated with advanced age (P = 0.017) and the presence of comorbidities (P = 0.011). While Laurén diffuse type (P < 0.001) and advanced stage (P = 0.029) were related to genomically stable (GS) subtype. GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival (DFS) and overall survival (OS) than other subtypes. Conversely, MSI subtype of GC had better survival in both classifications. Type of gastrectomy, pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSIONThe IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis, resembling the subtypes of the molecular classifications. Accordingly, this method of classification may represent a viable option for use in a clinical setting.     

美欧Biobank建设及管理现状研究

鉴于Biobank在未来医学研究中的作用,为了促进我国Biobank的健康发展,全文通过对国内外的Biobank的建设情况及其基本管理措施和经验进行了总结、归纳与分析,为我国Biobank的发展提供借鉴.     

妇科肿瘤病理诊断的新进展

本文结合近年来妇科病理诊断领域的新进展，从妇科细胞学、交界性肿瘤诊断进展、子宫内膜癌的分型、外阴和阴道间叶源性肿瘤、免疫组化在妇科病理诊断中的应用等方面进行了综述。     

Evolving entities and changing concepts in breast pathology

Among the evolving entities and changing concepts in breast pathology are those relating to columnar cell hyperplasia, pseudoangiomatous stromal hyperplasia, mucocele-like lesions, pleomorphic lobular carcinoma in situ, pseudo-Paget's disease of nipple, microinvasive carcinoma of breast, spindle cell metaplastic carcinoma, and minimal metastatic disease in axillary lymph nodes. Pathologists, as well as physicians involved in the management of breast diseases, need to be aware of these recent developments in breast pathology since the recognition and understanding thereof may have considerable clinical relevance.     

Window of opportunity studies: Do they fulfil our expectations?

Window of opportunity studies are trials in which patients receive one or more new compounds between their cancer diagnosis and standard treatment (mainly surgery). Patients are generally cancer treatment naïve. Tumor biopsies before and after the investigational treatment are collected for translational research. Similarly, anatomic and functional pre- and post-treatment imaging may be incorporated. Ideally, the investigational treatment is kept short to avoid delaying standard treatment.Window of opportunity trials may expedite drug development, improve our understanding of pharmacodynamic parameters, and help to identify biomarkers for better patient selection. They can, however, have major drawbacks including potential safety and logistical issues, delayed standard treatment, and a probable lack of patient benefit. By focusing on breast and head and neck cancers, in this paper we discuss the advantages, disadvantages and design of window of opportunity studies.     

肺癌图表演化见证转化性研究发展

肺癌从传统化疗到分子靶向,再到如今免疫治疗的转变,转化性研究发挥着无可替代的作用,其中图表演化更是见证一次次重大变迁,从“森林图”到“生存曲线图”,“瀑布图”,“蜘蛛图”再到最近的“时间线区域面积图”,纵向展示了肺癌治疗从群体逐渐向个体深入细化的理念和演进过程。尽管目前最新的免疫治疗炙手可热,但其研究结果并没有达到预期理想,同时传统的治疗手段仍然存在局限性,需要更深入探索。本文将从图表演化角度论述肺癌转化性研究的发展历程,剖析部分失败的外科临床研究,以期对未来肺癌治疗及图表演化有所启发。     

The diagnostic challenge of low-grade ductal carcinoma in situ

BackgroundDiagnostic agreement among pathologists is 84% for ductal carcinoma in situ (DCIS). Studies of interpretive variation according to grade are limited.MethodsA national sample of 115 pathologists interpreted 240 breast pathology test set cases in the Breast Pathology Study and their interpretations were compared to expert consensus interpretations. We assessed agreement of pathologists' interpretations with a consensus reference diagnosis of DCIS dichotomised into low- and high-grade lesions. Generalised estimating equations were used in logistic regression models of rates of under- and over-interpretation of DCIS by grade.ResultsWe evaluated 2097 independent interpretations of DCIS (512 low-grade DCIS and 1585 high-grade DCIS). Agreement with reference diagnoses was 46% (95% confidence interval [CI] 42–51) for low-grade DCIS and 83% (95% CI 81–86) for high-grade DCIS. The proportion of reference low-grade DCIS interpretations over-interpreted by pathologists (i.e. categorised as either high-grade DCIS or invasive cancer) was 23% (95% CI 19–28); 30% (95% CI 26–34) were interpreted as a lower diagnostic category (atypia or benign proliferative). Reference high-grade DCIS was under-interpreted in 14% (95% CI 12–16) of observations and only over-interpreted 3% (95% CI 2–4).ConclusionGrade is a major factor when examining pathologists' variability in diagnosing DCIS, with much lower agreement for low-grade DCIS cases compared to high-grade. These findings support the hypothesis that low-grade DCIS poses a greater interpretive challenge than high-grade DCIS, which should be considered when developing DCIS management strategies.     

Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview

The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.     

An analysis of the impact of pathology review in gynecologic cancer

Purpose: To analyze the impact of pathology review in gynecologic malignancies.

Methods and Materials: For all new gynecologic patients seen between December 2, 1993 and January 4, 1996, we conducted a retrospective chart review to determine if a pathology review by the institute’s consultant pathologist changed the diagnosis, and if so whether the change altered patient management. A total of 514 patients were seen, of whom 120 had cervical cancer, 226 had endometrial cancer, 122 had a primary ovarian or peritoneal malignancy, 9 had a vaginal malignancy, 28 had vulvar cancer, and 9 had a miscellaneous gynecologic malignancy.

Results: On pathology review the diagnosis changed for 200 of 599 specimens (33%). This altered management for 63 of 514 patients (12%). For patients with cervical cancer, the grade of tumor was the main change in pathologic diagnosis, with occasional change in the presence of lymph vascular invasion. These did not translate into patient management alterations. Eight patients (1.5%) had management alterations. The changes in depth of invasion and vascular invasion altered management for 3 patients. Changes in pap smears resulted in two management alterations, and changes in histologic diagnoses altered management for 3 cases. For endometrial primaries the changes in pathologic diagnosis included grade, depth of invasion, and the presence of cervical involvement. This did alter management in 40 cases (8%). For the ovarian malignancies, the main changes were grade, extent of disease, or histologic classification, some of which (10 patients, 2%) resulted in altered management. One patient with a vaginal lesion had the diagnosis changed, which did alter management. Of the patients diagnosed with vulvar cancer, the pathologic diagnosis changed for 11 patients. This included changes in grade and depth of invasion. This altered management of 2 patients. The remaining miscellaneous gynecologic malignancies had only two diagnosis changes that altered management.

Conclusions: Pathologic review of gynecologic malignancies is justified as it can alter patient management. In addition, the process facilitates cooperation of the multidisciplinary team and provides a valuable educational forum to enhance patient care.     

胃肠道间质瘤的临床病理研究

 胃肠道间质瘤（gastrointestinal stromal tumors，GIST）的概念提出后，其内涵几经变更，近年随着分子生物学研究的进展，才得以明确GIST是具有独特临床、病理及分子遗传学特征的肿瘤，不同于消化道真正的平滑肌或神经源性肿瘤。由于GIST分子靶向治疗的成功，GIST越来越受到人们的关注，因此，有必要对GIST的临床病理研究作一概述。