Rinsho byori. The Japanese journal of clinical pathology最新文献

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative treatment for many kinds of hematological diseases, but high transplant-related mortality (TRM), involving almost one quarter of patients who receive allo-HCT, remains problematic. TRM is mainly caused by infection (bacteria, virus, and fun- gus), acute or chronic graft versus host disease (GVHD), and/or organ dysfunction, such as-that involving the liver, lung, and/or kidney. Post-transplant infectious or noninfectious pulmonary complications are some of the important events after allo-HCT that may often be associated with TRM. The pre- or post-transplant pulmonary function test (PFT) plays an important role for the following reasons: 1) It may predict the devel- opment of noninfectious pulmonary complications such as chronic GVHD of the lung, i.e., bronchiolitis oblit- erans syndrome (BOS). 2) The diagnostic criteria and evaluation of the severity of BOS contain some PFT parameters. Therefore, we are not able to diagnose a patient with BOS nor evaluate the severity without PFT. 3) Pre- and post-transplant PFTs predict TRM and/or the overall transplant outcome. In order to improve the allo-HCT outcome, future studies of PFT in allo-HCT are needed. [Review].

Standardization based on clinical guidelines and personalization by molecular-targeted therapy have been introduced into the field of cancer treatment. To select patients appropriate for molecular-targeted drugs, various companion diagnostics have been developed. To catch up with revision of the clinical guidelines and progress of companion diagnostics, the effective utilization of "Guidelines for clinical examinations JSLM2015" is desirable. [Review].

The reversed clinicopathological conference (RCPC) is one of the most effective training methods to inter- pret routine laboratory data. In this RCPC, three specialists in laboratory medicine discussed laboratory data of a patient with upper gastrointestinal bleeding. Even though they interpreted the data with different methods, they arrived at the same conclusion. This discussion shows that it is possible to grasp the disease condition by RCPC training. In addition, combining laboratory data, the medical history, and physical find- ings helps improve the diagnostic ability. [Review].

Transplantation therapy for hematopoietic diseases is conducted by a team led by an attending physician. After transplantation, various adverse effects occur, such as graft versus host disease (GVHD) and thrombotic microangiopathy (TMA), recurrence, and engraftment failure. Therefore, attending physicians are busy with the evaluation of laboratory data, monitoring of immunosuppressants, use of blood products, and management of infectious diseases. Under such circumstances, laboratory technicians play various roles. Our blood test technicians conduct tests to predict outcomes desired by attending physicians and report them quickly and accurately. For that purpose, they must develop skills to interpret test results and examine morphological findings. In this report, we introduce our efforts to improve post-transplantation medical care. [Review].

At the annual meeting of the Japanese Society of Laboratory Medicine in Kobe in 2016, a joint symposium was held in cooperation between the Japanese Society of Laboratory Medicine and Japanese Association of Clinical Laboratory Physicians. We presented and discussed 5 cases at the Reversed Clinico-pathological Conference. Each case was analyzed by 5 new members of the Japanese Association of Clinical Laboratory Physicians, who had passed the examination for Certified Clinical Laboratory Physicians in 2015. After the presentation of their interpretation for basic laboratory tests, the correct diagnosis and useful practical advice were given by experienced Certified Clinical Laboratory Physicians. The first case involved hemolytic anemia due to valve replacement and multiple myeloma with the BJP type. The second case involved primary aldos- teronism with hypokalemia. The third case involved cold agglutination with a high value of MCHC. The fourth case involved pneumonia due to influenza virus. The last case involved diabetic ketoacidosis. All 5 cases were common rather than rare, and any members of the clinical laboratories may encounter them in routine work. A systemic analysis of routine laboratory data can sometimes directly lead to the correct diag- nosis using laboratory data alone and give doctors valuable clinical information on patients. Continuous daily efforts in systemic analysis will ensure that the evaluation skills of inexperienced Certified Clinical Laboratory Physicians in their hospitals will increase. Certified Clinical Laboratory Physicians in clinical laboratories are gatekeepers in every hospital from the viewpoints of both "medical audit" and "risk management".

International clinical trials need to achieve ISO 15189 Certification. However, there are a large number of challenges to be addressed before the achievement. While the retirement of experienced staff may result in insufficient knowledge, technology, quality assurance, or reliability, approaches to achieve ISO 15189 Certifi- cation are useful for human resource development and quality assurance. Furthermore, work efficiency improvement and standardization as part of such approaches can be incorporatea into programs for continuous education.

Advances in treatment have resulted in a high rate of sustained virological response in patients with hepati- tis C, whereas many asymptomatic carriers of hepatitis C virus (HCV) remain untreated. Therefore, HCV antibody screening holds great significance. However, the measurement principles or types of antigen used in screening vary according to the manufacturer, leading to discrepancies in the results obtained using differ- ent screening reagents. In this study, the performances of five HCV antibody screening assays - ARCHITECT HCV, ECLusys Anti-HCV II assay, HISCL HCV Ab assay, LUMIPULSE II Ortho HCV, and LUMIPULSE Presto Ortho HCV- were compared using 2,042 serum samples. The positive rates for the various assays ranged from 3.6% to 4.5%, and 1,937 and 70 samples were determined as negative and positive, respectively. Discordant results were obtained for 35 samples (1.7%). Additional confirmatory testing was performed on 105 samples that tested positive with at least one reagent. Thus, of the 35 samples with discordant results, 24 single-positive samples were highly likely to be false-positive and 5 single-negative sam- ples were likely to be truly positive. Considering that HCV antibody would not be missed by any assay, those showing no or minimal non-specific or crossover reactions would be ideal for HCV antibody screening. Indeed, further improvement of screening reagents is also needed.

A haplobank of induced pluripotent stem cell (iPSC) lines derived from healthy donors with homozygous human leukocyte antigen(HLA), which is called "an iPSC stock", has been under construction in Japan. The iPSC stock is expected to enable HLA matching of a majority of recipients and reduce the risk of trans- plant rejection. Full-scale operations began in FY2013, with the aim of covering 30-50% of the Japanese population by FY2017 and most of the population by FY2022 with the iPSC stock. A novel feeder-free and xeno-free culture system for iPSCs was developed to comply with regulatory safety standards. In 2015, a clinical-grade iPSC line with homozygous HLA of the highest-frequency haplotype was released as a first in the world. Other clinical-grade lines are being generated successively. If all goes to plan, the first clinical research using the iPSC stock will start in 2017. However, many challenges remain to ensuring the future of iPSC stock. In accordance with the progress of the latest research, safety issues regarding iPSC-based cell therapy are being monitored with much interest, and one of the major concerns is tumorigenicity. We have to continue to discuss the extent of genomic abnormalities that would or would not be acceptable in not only iPSC-derived products but also iPSC stock, taking into account the risks and benefits of cell therapy. It is also necessary to demonstrate the clinical efficacy of HLA matching, which is indicated to promote graft survival and reduce immunosuppressive drug use.

The development of genomic medicine has enabled us to perform contemporary clinical sequencing, while the acquisition of high-quality biospecimens and the appropriate handling of these materials are indispensable. We started Clinical Biobank, a novel system for on-demand-type banking, in 2014. During the 22 months from August 2014, we stored around 6,000 biospecimens from 1,700 patients, and most of them were obtained for diverse clinical research. The quality and amount of extracted DNA and RNA from PFPE samples were markedly high; thus, these samples are adequate for targeted amplicon sequencing using MiSeq (Illumina). In addition, we recently established the Division of Clinical Cancer Genetics for personalized cancer medicine. We obtain biospecimens including blood and tissue fixed using the PAXgene Tissue system, and the samples are immediately analyzed for targeted amplicon sequencing using MiSeq. The rest of the samples are stored after adequate procedures in a -80 degree freezer. We obtain DNA and RNA from PAX-fixed paraffin- embedded samples with a high quality and sufficient amounts for clinical sequencing after pathological evalua- tion. For three months, we examined 40 cancer patients and performed targeted exome sequencing. As a result, detection rates of actionable and druggable gene mutations were around 85 and 50%, respectively. We have also established the Clinical Biobank Study Group in Japan, collaborating with several universities and cancer centers. We believe that this novel biospecimen repository system will help to effectively estab- lish cancer clinical sequencing throughout Japan.

Many biobanks that have stored human clinical biospecimens have been established in Japan since 2005. Those biospecimens were mainly used in academia to perform basic research. The use of those biospeci- mens by industries, especially pharmaceutical or in vitro diagnostic companies, was restricted for ethical rea- sons. In this review, we discuss the importance of the standardization of the quality of biospecimens and workflow at biobanks for the utilization of specimens, and the possibility and issues regarding specimen use by industries.