Preoperative Fall Risk Assessment Score as a Prognostic Factor in Esophageal Cancer Patients after Esophagectomy.

The current study investigated the impact of preoperative fall risk assessment score (FRAS) on long-term prognoses in patients with esophageal cancer (EC). A total of 161 patients with EC who underwent curative surgery were classified into a high-risk (95, 41.0%) and low-risk (66, 41.0%) groups according to their FRAS. This study investigated the relationships between the FRAS and clinicopathological findings and prognoses. Accordingly, patients in the high-risk group were significantly older and had a significantly higher Charlson comorbidity index than those in the low-risk group. No significant difference was found in pathological findings between both groups. The high-risk group had significantly lower overall survival (OS) and relapse-free survival (RFS) rates than the low-risk group (p = 0.004 and 0.001, respectively). Multivariate analysis identified high FRAS as an independent prognostic factor for poor OS, with a hazard ratio of 1.75 (p = 0.033). Moreover, re-analysis of the data after excluding age as a category showed that the high-risk group had significantly worse OS (p = 0.004) and RFS (p = 0.003) than the low-risk group. The FRAS can, therefore, be considered a useful method for assessing frailty and a potential prognostic factor for EC.

Establishment and implementation of Cancer Genomic Medicine in Japan.

Approximately 1 in 2 Japanese people are estimated to be diagnosed with cancer during their lifetime. Cancer still remains the leading cause of death in Japan, therefore the government of Japan has decided to develop a better cancer control policy and launched the Cancer Genomic Medicine (CGM) program. The Ministry of Health, Labour, and Welfare (MHLW) held a consortium at their headquarters with leading academic authorities and the representatives of related organizations to discuss ways to advance CGM in Japan. Based on the report of the consortium, the CGM system under the national health insurance system has gradually been realized. Eleven hospitals were designated in February 2018 as core hospitals for CGM; subsequently, the MHLW built the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) as an institution to aggregate and manage genomic and clinical information on cancer patients, and support appropriate secondary use of the aggregated information to develop research aimed at medical innovation. As the first step in Japan's CGM in routine practice, in June 2019 the MHLW started reimbursement of 2 types of tumor profiling tests for advanced solid cancer patients using the national insurance system. Japan's CGM has swiftly been spreading nationwide with the collaboration of 167 hospitals and patients. The health and research authorities are expected to embody personalized cancer medicine and promote CGM utilizing state-of-the-art technologies.

Preoperative fall risk assessment score as a prognostic factor in gastric cancer patients after gastrectomy.

OBJECTIVE: Falls are related to frailty, which is known as an unfavorable prognosticator of gastric cancer. In this study, we investigated the influence of the fall risk assessment score on short- and long-term prognoses in patients with gastric cancer after gastrectomy. METHODS: A total of 430 patients who underwent gastrectomy for gastric cancer were included in this retrospective study. The fall risk assessment score was scored by nursing staffs on admission. We investigated the relationships between the fall risk assessment score and clinicopathological findings, postoperative outcomes and prognoses. We assigned patients with a fall risk assessment score ≥7 to the high-risk group (92 cases, 21.4%) and those with a fall risk assessment score <6 to the low-risk group (338 cases, 78.6%). RESULTS: There were no significant differences between the two groups in pathological stage of gastric cancer and postoperative complications, but the high-risk group had significantly longer postoperative hospital stays than the low-risk group (P < 0.001). The overall and the relapse-free survival rates in the high-risk group were significantly lower than those in the low-risk group. The high-risk group was one of the independent poor prognostic factors for overall survival, with a hazard ratio of 2.91 (P ≤ 0.001) in univariate analysis and a hazard ratio of 2.74 (P = 0.008) in multivariate analysis. CONCLUSIONS: While the fall risk assessment score is an objective and easy-to-use method to assess fall risk and frailty, it may present a prognostic factor in gastric cancer.

Assessment of TCR signal strength of antigen-specific memory CD8+ T cells in human blood.

Assessment of the quality and the breadth of antigen (Ag)-specific memory T cells in human samples is of paramount importance to elucidate the pathogenesis and to develop new treatments in various diseases. T-cell receptor (TCR) signal strength, primarily controlled by TCR affinity, affects many fundamental aspects of T-cell biology; however, no current assays for detection of Ag-specific CD8+ T cells can assess their TCR signal strength in human samples. Here, we provide evidence that interferon regulatory factor 4 (IRF4), a transcription factor rapidly upregulated in correlation with TCR signal strength, permits the assessment of the TCR signal strength of Ag-specific CD8+ T cells in human peripheral blood mononuclear cells (PBMCs). Coexpression of IRF4 and CD137 sensitively detected peptide-specific CD8+ T cells with extremely low background in PBMCs stimulated for 18 hours with MHC class I peptides. Our assay revealed that human memory CD8+ T cells with high-affinity TCRs have an intrinsic ability to highly express CD25. Furthermore, HIV-specific CD8+ T cells in chronic HIV+ subjects were found to display primarily low-affinity TCRs with low CD25 expression capacity. Impairment in the functions of HIV-specific CD8+ T cells might be associated with their suboptimal TCR signals, as well as impaired responsiveness to interleukin-2.

Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had ≥1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients.

Histological assessment of intra- and inter-institutional reliabilities in detection of desmoplastic reaction in biopsy specimens of early colorectal carcinomas.

We previously reported a relationship between depth of submucosal invasion of early colorectal carcinomas and desmoplastic reaction (DR). However, poor inter-observer agreement on the histopathological diagnosis of DR in biopsy specimens with hematoxylin and eosin (H&E) staining has been the major critique of this tool. In this study, reproducibility of the histopathological diagnosis of DR was evaluated. Furthermore, we investigated the possible improvement of the reproducibility after education about histological characteristics and tried to identify histological characteristics that are most important in the recognition of DR. A total of 34 H&E stained slides were included in this study and analyzed by three pathologists. Slides were reviewed before and after education about histological characteristics of DR. Kappa statistics were used to compare the inter-observer variability. We investigated the relationship between DR and histopathological factor. The inter-observer agreement during the first session varied between 0.30 and 0.63, which improved during the second session toward an agreement between 0.58 and 0.71. Myofibroblast proliferation associated with cancer invasion was found to be the most useful in the diagnosis of DR. In conclusion, the correct detection of myofibroblasts may facilitate the standardization of diagnosis of DR.

Standardization of whole slide image morphologic assessment with definition of a new application: Digital slide dynamic morphometry.

BACKGROUND: In histopathology, the quantitative assessment of various morphologic features is based on methods originally conceived on specific areas observed through the microscope used. Failure to reproduce the same reference field of view using a different microscope will change the score assessed. Visualization of a digital slide on a screen through a dedicated viewer allows selection of the magnification. However, the field of view is rectangular, unlike the circular field of optical microscopy. In addition, the size of the selected area is not evident, and must be calculated. MATERIALS AND METHODS: A digital slide morphometric system was conceived to reproduce the various methods published for assessing tumor budding in colorectal cancer. Eighteen international experts in colorectal cancer were invited to participate in a web-based study by assessing tumor budding with five different methods in 100 digital slides. RESULTS: The specific areas to be tested by each method were marked by colored circles. The areas were grouped in a target-like pattern and then saved as an .xml file. When a digital slide was opened, the .xml file was imported in order to perform the measurements. Since the morphometric tool is composed of layers that can be freely moved on top of the digital slide, the technique was named digital slide dynamic morphometry. Twelve investigators completed the task, the majority of them performing the multiple evaluations of each of the cases in less than 12 minutes. CONCLUSIONS: Digital slide dynamic morphometry has various potential applications and might be a useful tool for the assessment of histologic parameters originally conceived for optical microscopy that need to be quantified.

Symptom dimensions and needs of care among patients with schizophrenia in hospital and the community.

The purpose of the present paper was to examine the psychiatric symptom dimensions related to needs of care among patients with schizophrenia in hospital and in the community. Subjects were 217 patients with F2 ICD-10 diagnoses. Hospital patients included 102 inpatients (47.0%) in psychiatric long-term care units. Community patients included 115 outpatients (53.0%) living in their homes or residential facilities. Psychiatrists used the Brief Psychiatric Rating Scale (BPRS) to assess patients' psychiatric symptoms. Formal care providers assessed needs of care using a scale developed by the Committee on Case Management Guidelines for People with Mental Disabilities in Japan. Instrumental Activities of Daily Living (IADL) self-performance and difficulty were also measured using a scale from the Minimum Data Set-Home Care (MDS-HC). Multiple regression analyses were applied, using the symptom dimensions as dependent variables and needs of care as independent variables. Patient group (hospital or community) was also used as an independent variable. Hospital patients demonstrated more severe psychiatric symptoms and greater needs of care than community patients. Multiple regression analyses showed that the total needs of care were greater among male patients (B = 0.142, P = 0.005), hospital patients (B = 0.310, P < 0.001), patients with poor IADL self-performance (B = 0.217, P = 0.047), and patients with severe negative symptoms (B = 0.240, P = 0.002; R(2) = 0.515). The present results suggested an association between negative symptoms and needs of care in schizophrenia. Hospital patients had greater needs of care, even though their psychiatric symptoms were controlled for. Further research should examine the relationships between psychiatric symptoms and needs of care in a cohort study following patients when hospitalized and when living in the community.