Personalized Patient Care Research Articles

Engaging Oral Health Students in Learning Basic Science Through Assessment That Weaves in Personal Experience.

Learning basic science forms an essential foundation for oral health therapy and dentistry, but frequently students perceive it as difficult, dry, and disconnected from clinical practice. This perception is encouraged by assessment methods that reward fact memorization, such as objective examinations. This study evaluated use of a learner-centered assessment portfolio designed to increase student engagement with basic science in an oral health therapy program at the University of Sydney, Australia. The aim of this qualitative study based on focus groups was to investigate students' engagement with basic science courses following introduction of the portfolio. Three assessments were conducted in three subsequent semesters: one based on students' interest in everyday phenomena (one student, for example, explored why she had red hair); the second focussed on scientific evidence and understanding of systemic diseases; and the third explored relations between oral and general health. Students were encouraged to begin with issues from their personal experience or patient care, to focus on what they were curious about, and to ask questions they really cared about. Each student prepared a written report and gave an oral presentation to the entire cohort. After the portfolios were completed, the authors held focus groups with two cohorts of students (N=21) in 2016 and analyzed the results using Zepke's framework for student engagement research. The results showed that the students successfully interweaved personal experience into their studies and that it provided significant motivation for learning. The students described their learning in terms of connection to themselves, their peer community, and their profession. Many additional benefits were identified, from increased student engagement in all courses to appreciation of the relevance of basic science. The findings should encourage dental and allied dental educators to reconsider the effects of assessments and seek integrative methods to help students engage in meaningful knowledge production and understand that what they are learning goes beyond acquisition of scientific facts.

Viewpoint: The Practice Visit - An Obituary.

I was introduced to practice visits 25 years ago under the auspices of the ‘What Sort of Doctor’ scheme (colloquially ‘Whatsod’). These were peer-to-peer visits to practices and at their heart was a friendly but challenging discussion about what practices were actually doing to deliver good care, and how they might do it better. Their strength was that they were carried out by fellow GPs who knew that general practice is a difficult balance between efficiency and personal patient care. In the 1990s I visited each of 51 practices in and around St Helens in north west England. My central question was, ‘Would I want them to care for my mother?’ Some failed. But as I waited in some scruffy waiting rooms I frequently saw rather muddled patients coming to reception desks to be greeted by name. They were then helped to navigate …

Abstract P2-03-05: AJCC prognostic stage including oncotype DX®RS: Impact on breast cancer staging compared with traditional anatomic TNM stage

Abstract INTRODUCTION The recently published AJCC Cancer Staging Manual 8th edition, scheduled to be adopted into clinical practice in January 2018, proposes a new breast cancer (BC) Prognostic stage that includes histological grade, estrogen receptor (ER), progesterone receptor (PR), and HER2 status in addition to the traditional Anatomic TNM stage. In a further modification, patients with ER positive, HER2 negative, lymph node negative BC and an Oncotype DX® recurrence score (RS) of less than 11 will be assigned to Prognostic stage 1A irrespective of histological grade and size (up to 5cm). The changes have been proposed in recognition of the prognostic influence of these parameters and in attempt to improve personalised patient care. The aim of this study is to profile the impact on staging by comparing Prognostic stage, with and without RS, to traditional Anatomic stage, in a series of patients with early BC and an RS of less than 11. METHODS The study population comprised 127 patients with primary BC and an RS of less than 11, derived from a consecutive series of 729 patients with ER positive, Her2 negative, lymph node negative, primary BC whose tumors were tested using the Oncotype DX® multigene assay between November 2011 and December 2016. The median patient age was 57 years (35-78). Pathological tumour size was T1a (n=2), T1b (n=19), T1c (n=79) and T2 (n= 27). Median tumor size was 15mm. Histological tumour grade was grade 1 (n=14), 2 (n=98) and 3 (n=15). Each patient was assigned an Anatomic and Prognostic stage, with and without RS modification, according to the AJCC Classification of Cancer Staging, 8th edition. The three staging categories were compared and the impact on stage profiled. RESULTS Applying the traditional Anatomic Stage (TNM), 100 patients were assigned to stage IA (T1N0) and 27 patients to stage IIA (T2N0). Applying the Prognostic stage (without RS) 89 patients were assigned to stage IA, 33 to stage IB, four to stage IIA, and one to stage IIB. All patients were assigned to stage IA according to the Prognostic stage that includes a RS of < 11. Comparing Prognostic stage without RS to traditional Anatomic stage, 26.7% of patients (n=34) underwent a change in stage, 9.4% (n=12) to a higher stage and 17.3% (n=22) to a lower stage. 21.3% (n=27) of patients were down staged when comparing Prognostic stage including RS to traditional Anatomic stage. Comparing Prognostic stage including RS to Prognostic stage without RS, 29.9% (n=38) of patients were down staged. CONCLUSION Breast cancer staging is an important tool in guiding patient management. This study demonstrates that the introduction of the Prognostic stage and the modified Prognostic stage to include RS will alter the assigned stage in approximately 25% of patients with early BC. REFERENCE Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, Gershenwald JE et al (2016). AJCC Cancer Staging Manual, 8th edn. Springer, Chicago. Citation Format: O'Cearbhaill RM, Gannon JM, Devane LA, Prichard RS, Walshe J, McDermott EW, Quinn CM. AJCC prognostic stage including oncotype DX®RS: Impact on breast cancer staging compared with traditional anatomic TNM stage [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-05.

Genomic and Epigenomic Signatures in Ovarian Cancer Associated with Resensitization to Platinum Drugs.

DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer. In this study, we elucidated an epigenetic signature associated with platinum drug resensitization that may offer utility in predicting the outcomes of patients who are coadministered a DNA methyltransferase inhibitor. The ovarian cancer specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant ovarian cancer who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard-of-care chemotherapy regimen selected by the treating physician. Tumor biopsies or malignant ascites were collected from patients before treatment (day 1, cycle 1) or after treatment (after 2 cycles) for epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450). We defined 94 gene promoters that were hypomethylated significantly by guadecitabine, with 1,659 genes differentially expressed in pretreatment versus posttreatment tumors. Pathway analysis revealed that the experimental regimen significantly altered immune reactivation and DNA repair pathways. Progression-free survival correlated with baseline expression levels of 1,155 genes involved in 25 networks. In functional investigations in ovarian cancer cells, engineered upregulation of certain signature genes silenced by promoter methylation (DOK2, miR-193a, and others) restored platinum drug sensitivity. Overall, our findings illuminate how inhibiting DNA methylation can sensitize ovarian cancer cells to platinum drugs, in large part by altering gene expression patterns related to DNA repair and immune activation, with implications for improving the personalized care and survival outcomes of ovarian cancer patients.Significance: Epigenomic targeting may improve therapeutic outcomes in platinum-resistant and recurrent ovarian cancer in part by effects on DNA repair and antitumor immune responses. Cancer Res; 78(3); 631-44. ©2017 AACR.

Decoding the molecular switches of natriuretic peptides which differentiate its vascular and renal functions.

Heart failure (HF) is associated with high morbidity and mortality. Dysfunction of blood pressure and/or volume homeostatic processes result in lower perfusion and/or congestion. Treatment strategies exerting differential effects on pressure and volume mechanisms are critical in handling patients with HF. Atrial natriuretic peptides (ANPs) are a key hormone in maintaining circulation. It binds to NP receptor-A (NPR-A) on vasculature, kidneys and nervous system to lowers blood pressure and volume. It exerts a concentration-dependent pharmacological activity, and only increased renal excretion of water and sodium at low doses and vasodilation along with renal effects at slightly higher doses. Recently, we showed that K-Ring (conserved ring of krait venom NP) elicited only vasodilatory properties despite its ability to evoke NPR-A. Through systematic analysis of the structure-function relationships of K-Ring, we have delineated the molecular switches that control vasodilatory and diuretic properties of NPs in anesthetized rats. In the process, we have identified residues that - (a) differentiate vascular and renal functions, (b) affect heart rate and pulse pressure, (c) exhibit sustained effect on vasodilatory function and (d) forceful diuresis switches. Furthermore, we have shown these residues to have equivalent effects on ANP scaffold, thereby introducing modularity in designing function-based ANP analogs. By comparing the ability of designed NPs to evoke cGMP levels, we propose a hypothetical mechanism for the observed tissue-specific effects. The present study opens new avenues in the development of suitable therapeutic agents for personalized care for HF patients.

Technology in Medicine: Moving Towards Precision Management of Acute Kidney Injury.

The integration of modern information communication technology and technologically advanced equipment to routine clinical practice are important technological stepping stones in the management of patients with acute kidney injury (AKI). These tools improve practice and patient outcomes by supporting and individualizing all phases of AKI management. This narrative review describes the most recent bedside technological advances in AKI diagnosis, renal replacement therapy education, prescription, monitoring, delivery, and measurement of outcomes with an emphasis on providing highly personalized patient care.

Credible ecological inference for medical decisions with personalized risk assessment

This paper studies an identification problem that arises when clinicians seek to personalize patient care by predicting health outcomes conditional on observed patient covariates. Let y be an outcome of interest and let (x=k, w=j) be observed patient covariates. Suppose a clinician wants to choose a care option that maximizes a patient's expected utility conditional on the observed covariates. To accomplish this, the clinician needs to know the conditional probability distribution P(y|x=k, w=j). It is common to have a trustworthy evidence‐based risk assessment that predicts y conditional on a subset of the observed covariates, say x, but not conditional on (x, w). Then the clinician knows P(y|x=k) but not P(y|x=k, w=j). Research on the ecological inference problem studies partial identification of P(y|x, w) given knowledge of P(y|x) and P(w|x). Combining this knowledge with structural assumptions yields tighter conclusions. A psychological literature comparing actuarial predictions and clinical judgments has concluded that clinicians should not attempt to subjectively predict patient outcomes conditional on covariates that are not utilized in evidence‐based risk assessments. I argue that formalizing clinical judgment through analysis of the identification problem can improve risk assessments and care decisions. Ambiguity clinical judgment partial identification patient care C14 I19

Bladder cancer: Multi-omic profiling refines the molecular view.

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease for which treatment has, historically, lagged behind that of other solid tumour types. A more detailed understanding of the biology of individual tumours, and the identification of molecular features providing prognostic and predictive information is key to the application of personalized care for patients with MIBC. The publication of a study of 412 samples now provides such data.

Cell-surface marker discovery for lung cancer.

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients.

Measuring the Quality of Personal Care in Patients Undergoing Radiotherapy for Prostate Cancer

AimsTo describe the quality of the non-technical component of the care (personal care) of patients receiving radical radiotherapy for prostate cancer and to identify elements of personal care that should be priorities for quality improvement. Materials and methodsOne hundred and eight patients undergoing radiotherapy for localised prostate cancer completed a self-administered questionnaire that asked them to rate the importance of 143 non-technical elements of care and to rate the quality of their own care with respect to each element. The elements that a patient rated as both ‘very important’ and less than ‘very good’ were deemed to be his priorities for improvement. The priorities of the population were established by ranking the elements based on the percentage of patients who identified them as a priority (importance/quality analysis). ResultsThe response rate was 65%. The percentage of elements rated ‘very good’ varied from patient to patient: median 79% (interquartile range 69–92%). The percentage of elements rated either ‘very good’ or ‘good’ was higher: median 96% (interquartile range 86–98%). Nonetheless, almost every patient rated at least some elements of his care as less than optimal, regardless of the cut-off point used to define optimal quality. Patients assigned their lowest quality ratings to elements relating to the quality of the treatment environment and comprehensiveness of additional services available to them. However, patients rated most of these elements as relatively unimportant, and importance/quality analysis identified elements of care relating to communication of information about the disease and its treatment as the highest priorities for quality improvement. ConclusionsMost patients rated most elements of their personal care as very good, but almost all were able to identify some elements that were less than optimal. When ratings of quality were integrated with ratings of importance, elements relating to communication emerged as the patients' highest priorities for quality improvement.

Epigenetic research in multiple sclerosis: progress, challenges, and opportunities.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, integrate influences from the genes and the environment to regulate gene expression accordingly. Studying epigenetic modifications, which are stable and reversible, may provide an alternative approach to better understand and manage disease. We here aim to review findings from epigenetic studies in MS and further discuss the challenges and clinical opportunities arising from epigenetic research, many of which apply to other diseases with similar complex etiology. A growing body of evidence supports a role of epigenetic processes in the mechanisms underlying immune pathogenesis and nervous system dysfunction in MS. However, disparities between studies shed light on the need to consider possible confounders and methodological limitations for a better interpretation of the data. Nevertheless, translational use of epigenetics might offer new opportunities in epigenetic-based diagnostics and therapeutic tools for a personalized care of MS patients.

Clinical Features of Psoriatic Arthritis: a Comprehensive Review of Unmet Clinical Needs

Psoriatic arthritis (PsA) is a form of inflammatory arthritis (IA) affecting approximately 0.25% of the population. It is a heterogeneous disorder associated with joint damage, disability, disfiguring skin disease and in severe cases, premature mortality. Inherently irreversible and frequently progressive, the process of joint damage begins at, or before, the clinical onset of disease. Early recognition and intervention is thus crucial to patient outcome. At disease onset, however, PsA often resembles other forms of arthritis-especially rheumatoid arthritis (RA). Despite the similarities between PsA and RA, their distinctive pathologies require different treatments. For example, drugs that are effective in RA may not be effective in PsA and can even cause adverse effects. Since there is no currently validated test for PsA, the diagnosis is often missed or delayed and this has functional consequences for the patient. In the context of PsA and RA, making an accurate diagnosis is not the only challenge faced by rheumatologists. Choosing an effective and safe medication to manage the disease is another significant challenge and currently approximately 40% achieve meaningful responses such as minimal disease activity status. For the patient, several months may be lost as a result of trial and error testing-meanwhile, irreversible joint damage may occur. Clearly, more effective clinical tests are urgently needed to improve personalised patient care in PsA. Specifically, there is need to develop minimally invasive tests predictive of diagnosis, response to treatment and radiographic progression. In this review, we examined the biomarker development process, highlighted the importance of qualifying unmet clinical needs and emphasised the challenges that impede biomarker studies. We have compiled a comprehensive list of potentially clinically relevant biomarkers in PsA and provided a summary of proteomic technologies that might usefully support additional biomarker research in PsA.

Abstract 1528: Forecasting novel therapies by understanding the role BRD4 in regulating the Notch3 signaling in ovarian cancer

Abstract Advances in cancer research have led to the rapid development of novel drug therapies designed for optimal personalized patient care. Despite this surge of treatments, there is still a challenge in accurately predicting the most effective targeted therapy for a specific cancer. Additionally, the potential of systematically identifying and re-purposing currently existing therapeutics designed for one specific cancer to treat other malignancies remains understudied. To address this problem, our group has developed an integrative computational therapy-forecasting algorithm. This algorithm incorporates data from The Cancer Genome Atlas (TCGA) as well as molecular and survival correlations to identify candidate anti-tumor drugs that can be re-purposed for other malignancies by targeting novel pathways. Our computational analysis predicted that bromodomain inhibitors, which inhibit bromodomain-containing proteins such as BRD4, would target the Notch3 pathway in high-grade serous ovarian carcinoma (HGSC). Upregulation of Notch3 plays a crucial role in HGSC tumorigenesis and is associated with worse patient survival. Current Notch3 targeted therapies are not effective, thus designing therapeutic strategies to target Notch3 are critical for HGSC. We hypothesize that inhibition of BRD4 is an effective therapeutic target in HGSC by downregulating the Notch3 pathway. Current in vitro results demonstrated that BRD4 inhibition either by using chemical inhibitors or siRNA results in a decrease in HGSC cell viability by both MTT and 2-D colony formation assays. Furthermore, inhibition of BRD4 resulted in a decrease in both Notch3 transcription and protein levels. Given that BRD4 regulates gene transcription, we performed chromatin immunoprecipitation (ChIP) and observed that BRD4 was present in the Notch3 gene promoter. These findings suggest that by inhibiting BRD4 in HGSC, we can target Notch3 and biologically validates our initial in sillico analysis. The successful completion of this project could have major implications for development of personalized therapies not only for HGSC but for other cancers as well. Note: This abstract was not presented at the meeting. Citation Format: Alejandro Villar-Prados, Sherry Y. Wu, Jason Roszik, Anil K. Sood, Margaret I. Engelhardt. Forecasting novel therapies by understanding the role BRD4 in regulating the Notch3 signaling in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1528. doi:10.1158/1538-7445.AM2017-1528

중년기 요양 환자의 건강사정도구 개발

Purpose: This was a methodological study to develop a valid and reliable health assessment tool for middle-aged adults in long-term care settings (HATMAL). Methods: At the first stage of this study, initial 56-items HATMAL were derived via literature review, survey for needs assessment, and focus group interviews with experts. At the second stage, 54 items HATMAL were finalized via content validity test with 5 experts and a pilot study with 30 nurses. At the third stage, validity and reliability tests were conducted with 100 middle-aged patients in a long-term care hospital. Data were analyzed by factor analysis using SPSS 18.0 program. Results: Exploratory factor analysis resulted in 3 factors; functional assessment, symptom assessment, and comfort assessment. These 3 factors explained 83.8% of total variance and construct validity was confirmed. Test-retest reliability was .67 for appetite changes, .76 for regulating for behavior problems, and 1.0 for other items. Conclusion: Results indicate that HATMAL is valid and reliable to assess the health for middle-aged patients in long-term care settings. This study would contribute to provide more effective personalized treatment and care for middle-aged patients in long-term care settings considering their own characteristics.

A Statewide Survey Report of Roles and Responsibilities in Current Utah Care Management Processes

Measure current roles and responsibilities of care managers in the state of Utah. All settings of health care including inpatient, outpatient, community, payer, post-acute, and transitional care settings. A quantitative descriptive survey design was used to assess and describe current care management roles and responsibilities of 191 care managers within the state of Utah. Quantitative variables of roles and responsibilities were collected an electronic database (REDCap). Major results conclude that care managers spend most of their time on direct patient interactions including discharge planning, population care, and utilization review. These care managers are highly experienced in their field, with most being in their professional practice for more than 10 years. Most of the care managers are bachelor's prepared nurses. To create or expand care management processes to meet the goals of health care reform, systems first need to know what care managers/coordinators are doing and where their current focus on care presides. Educators, leaders, and, indeed, the care managers themselves are a part of preparing this dynamic workforce. The major responsibility of care management continues to be direct patient interactions, meaning that care managers are performing vital interpersonal patient interaction needed to achieve highly personalized patient care with assurances of quality and safety. No matter the name-care management, case management, or care coordination-these activities are an essential part of health care, with highly specialized skills that promote patient engagement and activation.

Pharmacists help patients get started on hepatitis C regimens.

A pharmacist-led program for the treatment of chronic hepatitis C is providing personalized care for patients in New Jersey and helping their treatment plan stay on track. The program, operated out of the Hunterdon Medical Center’s infectious diseases (ID) clinic in Flemington, was developed in

Basic and New Techniques for MRI of the Breast

: MRI of the breast has evolved as a non-invasive imaging modality and is ideally suited for several indications e.g. pre-operative staging and screening in women at increased risk for breast cancer. The widespread use opens also the discussion on over-diagnosis if only 20 - 30 out of 100 MRI - guided breast biopsies lead to the diagnosis of breast cancer. Thus MRI based strategies are needed to significantly reduce the number of unnecessary biopsies by decreasing over-diagnosis. In their development cancer have acquired several functional capabilities, which are defined as the hallmarks of cancer. For a deeper understanding of the hallmarks of cancer, and, consequently, improved personalized patient care, diagnostic tests must be multilayered and complex to identify the relevant underlying processes of cancer development and progression. Contrast-enhanced MRI (CE-MRI) is the most sensitive test for breast cancer detection, with a good specificity. Recently, several functional parameters on MRI have been assessed for breast imaging and this combined application is defined as multiparametric imaging. Multiparametric imaging with different functional MRI parameters (mpMRI) visualizes and quantifies the functional processes of cancer development and progression at multiple levels, and provides specific information about the hallmarks of cancer. MpMRI of the breast improves diagnostic accuracy in breast cancer, obviates unnecessary breast biopsies, and enables an improved assessment and prediction of response to neoadjuvant therapy. This lecture will provide a comprehensive overview of the current strategies and emerging techniques for mpMRI of the breast.

Increased Frequency and Vasculogenic Potential of Endothelial Colony-Forming Cells in Patients with Kaposi’s Sarcoma

Kaposi's sarcoma (KS) is characterized by hyperproliferation of spindle cells that have an endothelial origin and assume their characteristic features upon infection with human herpesvirus-8, the causative agent for KS. The multifocal nature of KS suggests that spindle cells derive from circulating HHV8-infected precursors that yet lack identification. We investigated whether endothelial colony-forming cells (ECFCs) obtained from KS patients may be putative precursors of spindle cells by assessing whether their invitro behavior may evoke the invivo behavior of KS spindle cells. We isolated and cultured ECFCs from the blood of 83 patients with classic KS and compared them with ECFCs obtained from 86 healthy donors. ECFCs were highly increased in the blood of classic KS patients; they showed higher proliferative and vasculogenic potential and higher production of IL-6 than control ECFCs. Similarly to spindle cells in KS lesions, a variable proportion of cells within each ECFC colony expressed the human herpesvirus-8 latency-associated nuclear antigen. ECFCs obtained from classic KS patients evoked KS spindle cell behavior, thus supporting the hypothesis that ECFCs may be putative precursors of spindle cells. ECFCs can therefore represent a noninvasive tool for studying KS and screening drug activity, thus possibly guiding personalized care for KS patients.

Whole Slide Imaging for Analytical Anatomic Pathology and Telepathology: Practical Applications Today, Promises, and Perils.

Whole slide imaging (WSI) offers a convenient, tractable platform for measuring features of routine and special-stain histology or in immunohistochemistry staining by using digital image analysis (IA). We now routinely use IA for quantitative and qualitative analysis of theranostic markers such as human epidermal growth factor 2 (HER2/neu), estrogen and progesterone receptors, and Ki-67. Quantitative IA requires extensive validation, however, and may not always be the best approach, with pancreatic neuroendocrine tumors being one example in which a semiautomated approach may be preferable for patient care. We find that IA has great utility for objective assessment of gastrointestinal tract dysplasia, microvessel density in hepatocellular carcinoma, hepatic fibrosis and steatosis, renal fibrosis, and general quality analysis/quality control, although the applications of these to daily practice are still in development. Collaborations with bioinformatics specialists have explored novel applications to gliomas, including in silico approaches for mining histologic data and correlating with molecular and radiologic findings. We and many others are using WSI for rapid, remote-access slide reviews (telepathology), though technical factors currently limit its utility for routine, high-volume diagnostics. In our experience, the greatest current practical impact of WSI lies in facilitating long-term storage and retrieval of images while obviating the need to keep slides on site. Once the existing barriers of capital cost, validation, operator training, software design, and storage/back-up concerns are overcome, these technologies appear destined to be a cornerstone of precision medicine and personalized patient care, and to become a routine part of pathology practice.

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology.

Purpose Molecular testing of colorectal cancers (CRCs) to improve patient care and outcomes of targeted and conventional therapies has been the center of many recent studies, including clinical trials. Evidence-based recommendations for the molecular testing of CRC tissues to guide epidermal growth factor receptor (EGFR) -targeted therapies and conventional chemotherapy regimens are warranted in clinical practice. The purpose of this guideline is to develop evidence-based recommendations to help establish standard molecular biomarker testing for CRC through a systematic review of the literature. Methods The American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) convened an Expert Panel to develop an evidence-based guideline to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for patients with CRC. A comprehensive literature search that included over 4,000 articles was conducted to gather data to inform this guideline. Results Twenty-one guideline statements (eight recommendations, 10 expert consensus opinions and three no recommendations) were established. Recommendations Evidence supports mutational testing for genes in the EGFR signaling pathway, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize molecular testing for predictive and prognostic molecular biomarkers involve selection of assays, type of specimens to be tested, timing of ordering of tests and turnaround time for testing results. Additional information is available at: www.asco.org/CRC-markers-guideline and www.asco.org/guidelineswiki.