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

Serum biomarkers are playing an increasingly important role in the management of liver diseases. In this article, we provide an overview of the biomarkers that are currently used for the primary diagnosis of liver fibrosis, hepatocellular carcinoma (HCC), and occult hepatitis B virus (HBV) infection. Because liver fibrosis is a significant risk factor for hepatocarcinogenesis, monitoring its progression is important for predicting and preventing HCC. In 2015, the novel liver fibrosis glycobiomarker Wisteriaflori- bunda agglutinin-positive Mac-2 binding protein (WFA'-M2BP, M2BP glycan isomer [M2BPGiI) became available in Japan. The HISCL M2BPGi assay is fully automated, rapid (17 minutes), and requires only a small sample volume (10 μL). Serum tumor markers are noninvasive and valuable for the management of patients with a high risk of de- veloping HCC. Although a-fetoprotein (AFP) has been commonly used, its insufficient sensitivity and specificity for early-stage HCC make it unsuitable for managing patients at high risk of developing HCC. However, a combination of AFP and protein induced by vitamin K absence factor II (PIVKA-II), or Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and PIVKA-II are currently being evaluated for HCC pre- diction. Recently, a highly sensitive chemiluminescent enzyme immunoassay (CLEIA) for HBsAg detection by Lumipulse HBsAg-HQ has been reported as the latest clinical application. Although the sensitivity of this assay ( ≥5 mIU/mL) is 10-fold higher than that of the conventional assay, it is still lower than that of the HBV-DNA assay. HBsAg-HQ will be applied for detecting occult HBV infection and HBV reactivation. [Review].

The advent and long-term use of tyrosine kinase inhibitors in molecular target therapy for chronic myeloid leukemia have resulted in a marked improvement of treatment outcomes. This has changed'the algorithm of the laboratory process for the diagnosis and therapeutic monitoring of chronic myeloid leukemia. It includes defining the molecular typing of BCR-ABL1 to establish the diagnosis, and a quantitative and/or high- sensitivity assay for minimal residual disease to evaluate the treatment response. Along with improved long-term survival outcomes, new issues have arisen regarding the best index to use for the improved clinical outcomes, such as treatment-free remission. To this end, clinical and laboratory monitoring of CML patients has been investigated. Novel methodologies and technologies have been applied to improve decision-making on patient care, tailoring the treatment to the individual characteristics of each patient, including an early index for the treatment response and deeper molecular response to realize treatment-free survival, and BCR-ABLI kinase domain mutation screening for refractory disease. In response to the advancement and applications of these emerging technologies, proper laboratory practice with the quality assurance of testing is expected. [Review].

Genetic testing of hematological malignancy is-.indispensable to categorize and diagnose leukemia. The quantitation of fusion gene mRNA built up by chromosomal translocation including BCR-ABL1 (major, minor), RUNX1-RUNX1T1, and PML-RARA and detection of the JAK2 (V617F) mutant gene are performed by our- selves in our hospital. Efficient, practical use is necessary because the number of medical technologists is limited and numbers of tests are increasing annually. The detection of leukemic cells is important in hematological tests. In addition, experienced medical technologists can predict the existence of fusion mutant genes. In this report, we introduce our experience regarding the practical use and operation of biomarkers for leukemia. Medical technologists take advantage of peripheral blood tests for screening, such as the complete blood count (CBC), hemogram, fibrin and fibrinogen degradation products (FDP), and the quantitation of fusion gene mRNA, which offers a definitive diagnosis including BCR-ABL1, RUNX1-RUNX1T1, and PML-RARA, and genetic tests are performed efficiently. [Review].

The incidence of epilepsy is high in infants/children and elderly persons. Patients with epilepsy account for approximately 1% of the population. This chronic cerebral disorder is characterized by repeated epileptic seizures related to excessive excitation of the brain, and it is important to reduce such seizures in life. Therapeutic drug monitoring (TDM) is useful for evaluating the treatment response and checking for adverse effects. When interpreting the results of measurement of the blood concentrations of antiepileptic drugs, the duplication of various factors must be understood. In this article, matters that clinical technologists face in routine work are presented/arranged so that the results of TDM may be adequately interpreted. In 270% of patients with epilepsy, as a nervous disease, seizures may be reduced by administering adequate therapy with antiepileptic drugs; the response rate is high. If measurements deviate from the reference range, clini- cal technologists should utilize their specialized knowledge and adequately evaluate the values obtained, con- tributing to drug therapy. [Review].

Most of germ cell tumor is gonadal origin. However 5% of malignant germ cell tumors appear in extragonadal organs. Because extragonadal germ cell tumors (EGGCTs) are found anywhere on the midline such as pineal gland, mediastinum and retroperitoneum, the origin of this type of tumor is controversial. EGGCTs are often seen between childhood and young adult; an elderly patient with EGGCT is rarely met. Here we report a case that an abnormal alpha-fetoprotein (AFP) fractionation pattern was helpful for diagnosis of retroperitoneal germ cell tumor. A presenile man with hepatic cirrhosis caused by chronic hepatitis C showed an intraperitoneal tumor-like mass on computed tomography and thus hepatocellular carcinoma was suspected. A serological test re- vealed elevated total AFP level and AFP-L3%. The latter is the proportion of fucosylated AFP on the lectin-affinity based fractionation. Noticeably the fractionation pattern of AFP of this patient was abnormal, sug- gesting a diversity of lectin-affinity of AFP in germ cell tumors. This patient also showed an atypical in- crease in beta human chorionic gonadotropin (8hCG). We suggest the measurement of 6hCG for early differ- ential diagnosis of retroperitoneal germ cell tumor and hepatocellular carcinoma when an abnormal AFP frac- tionation pattern was detected in a patient with suspected hepatocellular carcinoma. [Short Communication].

Antiarrhythmic drugs (AADs) can exhibit lethal adverse effects including proarrhythmia. To avoid these adverse effects, therapeutic drug monitoring (TDM) provides a therapeutic benefit. Recently, the Japanese Circulation Society and Japan TDM Society collaborated to do publish "Guidelines for TDM of Cardiovascular Drugs". Class I AADs exert strong sodium channel-blocking effects. The initial dose should be set using a nomogram. When using a beta blocker, an electrocardiogram and heat rate monitoring are more useful than TDM. Pulmonary toxicity is frequently observed in patients treated with amiodarone. TDM of amiodarone and its active metabolite desethylamiodarone is available to assess the risk of pulmonary toxicity. The ther- apeutic range of bepridil is 250-800 ng/mL. Exceeding this range may result in abnormal QT prolongation and the development of torsade de pointes. Digitalis intoxication should be avoided. Its therapeutic range partially overlaps with its toxic range. In patients with congestive heart failure, the serum concentration of digoxin should be maintained at a lower range. In summary, regarding arrhythmia therapy using AADS, safety should be more important than efficacy. Appropriate TDM is recommended. [Review].

Objective: Rapid and accurate detection of norovirus is essential for the prevention and control of the out- breaks. The aim of this study is to compare the fully automated real-time reverse transcriptase-polymerase chain reaction method (EV-kit) with the conventional immunochromatography method (IC) for diagnosis of norovirus, using one-tube reverse transcriptase-polymerase chain reaction (RT-PCR) analysis as the gold standard.

Methods: Between November 2013 and March 2014, clinical data and fecal specimens (53 bulk stools, 41 rectal swabs) were collected from 94 patients who visited the Department of General Medicine, Juntendo University Hospital for acute diarrhea. The sensitivity and specificity of each study test was determined by comparing with RT-PCR, and reproducibility was analyzed by determining Cohen's kappa coefficients.

Results: Of 94 specimens, 35(37%, 26 bulk stools, 9 rectal swabs) were positive for norovirus antigen by RT-PCR. The sensitivity, specificity, and Cohen's kappa coefficient of the EV-kit were 91% (32/35), 88% (52/59), and 0.778, respectively; those of the IC were 54% (19/35), 90% (53/59), and 0.468, respectively. For rectal swab testing, the sensitivity was 89% (8/9) for the EV-kit and 33% (3/9) for IC, ana that for bulk stool testing was 92% (24/26) for the EV-kit and 62% (16/26) for IC.

Conclusions: Use of the EV-kit was significantly more sensitive than was IC testing, taking RT-PCR analy- sis as the gold standard. Rectal swab or bulk stool specimens may be adequate for the detection of norovirus antigen when the EV-kit is used. [Original].

In comprehensive health check performed in Japan, many errors have been found that were caused by man- ually transcribing family doctor's reports or commissioned health check company's reports to Medical Examina- tion Record and Results Report. Since those errors included unit's error of blood tests that caused digits differ- ences, we hereby present the result of an investigation on current situation of blood test reporting units in Japan. Results showed that, in prefectural medical institutions, only a few facilities used international units in reporting units of blood tests. However, most of the domestic or overseas quality control programs used in- ternational units, except for that conducted by the Japan Medical Association. We consider that it might be possible to prevent medical malpractices caused by erroneous judgment on health check results, by unifying the blood test reporting units upon sharing patients' information among medical facilities. [Letter].

In cancer immunotherapy, there are two major strategies for the treatment of cancers: the use of immune system modulators, and the inhibition of immune checkpoints. The immune system modulators including cytokines, antibodies, and Toll-like receptor (TLR) agonists activate the host immune response against tu- mors. Recently, the various mechanisms of immune suppressive systems have been extensively examined. Immune checkpoints are molecules involved in immune suppressive systems and the progression of various cancers. In tumor-bearing animals, the expression of some immune checkpoints increases, and many can- cers are protected from the host immune system by such immune checkpoints. Therefore, immune check- point inhibitors have recently been drawing much attention in cancer immunotherapy. Immune system modulators or immune checkpoint inhibitors are used against cancers as monotherapy. However, immune system modulators such as TLR agonists also induce immune checkpoints. Recently, we reported that combination therapies with immune system modulators and immune checkpoint inhibitors had more marked anti-tumor effects compared with monotherapies in a tumor-bearing mouse model. In previous reports, TLR7 agonist (imiquimod) or alpha-galactosylceramide (GalCer) was used as an immune system modulator, and the expression of indoleamine 2,3-dioxygenase (IDO) or inducible nitric oxide synthase was inhibited in cancer therapies with imiquimod or GalCer. These combination therapies can potently induce the tumor- antigen-specific cellular immune response. Moreover, the IDO activity well reflects the disease progression of hematological malignancy clinically, and the measurement of IDO activity is useful to assess the prognosis during chemotherapies. Thus, immune checkpoints such as IDO are helpful for the development of new cancer therapies and diagnosis. [Review].

Purpose: We aimed to evaluate the performance of an HIV antigen-antibody combination assay (fourth-generation) by comparing it with second generation assays that detect anti-HIV.

Methods: A total of 105,439 HIV screening tests were performed from January 2004 to March 2015; the second - and fourth generation assays were used for 75,302 and 30,137 samples, respectively. Samples positive on a screening test were confirmed by anti-HIV-1 western blotting (WB) and nucleic acid amplification. By the results of confirmation tests, the efficacies of the second and fourth generation assays were estimated. The clinical backgrounds with false-positive samples were examined.

Results: Of 75,302 samples, 136(0.18%) were positive by the second-generation assay; 14 were confirmed positives, and 122 were false positives. Of 30,137 samples, 18(0.06%) were positive by the fourth-generation assay; 6 were confirmed positives, and 12 were false positives. The reliability of the positives by fourth-generation assay was significantly improved (p=0.006) Samples form individuals with malignant neoplasms were frequently false positive by both the second and fourth-generation assays. Of 67 samples performed by WB, 10 samples, including 6 from patients with a malignancy, showed indeterminate results. All indeterminate samples were found to have antibodies responding to HIV core protein.

Conclusion: The fourth-generation assay had satisfactory reliability of the positives for HIV screening. Antibodies responding to HIV core protein may result in false positive HIV screening tests. [Original]