Searches / Rinsho Byori. The Japanese Journal Of Clinical Pathology[JOURNAL]

Rinsho Byori. The Japanese Journal Of Clinical Pathology[JOURNAL]

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[JAK2, CALR].

Ikejiri M

Rinsho Byori · 2017 Jan · PMID 30695513

Representative diseases of BCR/ABL-negative myeloproliferative neoplasms (MPN) are polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). It was reported in 2005 that there is a common ge... Representative diseases of BCR/ABL-negative myeloproliferative neoplasms (MPN) are polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). It was reported in 2005 that there is a common genetic mutation in Exon 14 of the JAK2 gene in MPN cases. The gene mutation is a point mutation at which the 617th amino acid of the JAK2 protein is substituted from valine to phenylalanine and is referred to as the JAK2 V617F mutation. Subsequently, JAK2 Exon 12 mutation, MPL gene mutation, and CALR gene mutation were detected in 2013, and it was revealed that in almost all cases of BCR/ABL- negative MPN, any gene mutation could be involved as a driver gene mutation. As a result, in the WHO classification 2016, gene mutation analyses of JAK2, MPL, and CALR were incorporated into the diagnostic criteria. Analysis of gene mutation is indispensable for the diagnosis of MPN. Also, its importance as an inspection item is increasing. [Review].

[Evolution of BCR-ABL1 Testing for Chronic Myeloid Leukemia Under Tyrosine Kinase Inhibitor Treatment].

Miyachi H

Rinsho Byori · 2017 Jan · PMID 30695512

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 labor... 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].

[FLT3 Mutations in Acute Myeloid Leukemia].

Shoji T, Kida Y, Yamashita K … +1 more , Ichiyama S

Rinsho Byori · 2017 Jan · PMID 30695511

FMS-like tyrosine kinase 3 (FLT3), a class III tyrosine kinase receptor, plays an important role in the pro- liferation, survival, and differentiation of hematopoietic stem/progenitor cells. Approximately 30% of pa- tien... FMS-like tyrosine kinase 3 (FLT3), a class III tyrosine kinase receptor, plays an important role in the pro- liferation, survival, and differentiation of hematopoietic stem/progenitor cells. Approximately 30% of pa- tients with cytogenetically normal acute myeloid leukemia (CN-AML) harbor FLT3 mutations. The most frequent FLT3 mutations are internal tandem duplications (ITDs) in the juxtamembrane domain. FLT3-ITD mutations cause ligand-independent dimerization of FLT3 and the constitutive activation of its downstream signaling pathways, such as PI3K/AKT, A4APK/ERK, and STAT5, leading to dysregulated cellular prolifera- tion. The relapse risk of CN-AML patients with FLT3-ITD is higher and the overall survival (OS) of such patients is shorter than those of patients with wild-type FLT3. Recently genome-wide studies with next-generation sequencing have suggested that mutational combinations of genes related to signal transduction, transcription, splicing, cancer suppressors, and epigenetics contribute to the pathogenesis of AML. These mutations including FLT3-ITD may be prognostic factors facilitating the risk stratification for CN-AML. The point mutations D835/I836 in the tyrosine kinase domain (TKD) are detected in 5-7% of AML patients. The clinical relevance of these FLT3-TKD mutations remains unclear. FLT3-TKD mutations are detected even in patients treated with FLT3 inhibitors as secondary mutations, suggesting that the mutations are as- sociated with the resistance. Therefore, the detection of these mutations might provide us with the opportunity to consider appropriate treatment for patients. The molecular abnormalities in AML patients give us insights into the pathology of AML and clinically significant information required for the diagnosis, prognosis, and treatment decisions. [Review].

[The Significance of Genetic Testing for Acute Promyelocytic Leukemia].

Satoh Y, Masuda A, Yatomi Y

Rinsho Byori · 2017 Jan · PMID 30695510

The majority of patients with acute promyelocytic leukemia (APL) harbor the t (15;17) (q22;q12) transloca- tion, which results in the expression of PML-RARA mRNA. All-trans retinoic acid (ATRA) is a representa- tive mole... The majority of patients with acute promyelocytic leukemia (APL) harbor the t (15;17) (q22;q12) transloca- tion, which results in the expression of PML-RARA mRNA. All-trans retinoic acid (ATRA) is a representa- tive molecular-targeted drug and is directed against PML-RARA. Therefore, the detection of PML-RARA mRNA has become indispensable for the diagnosis of APL and the decision regarding the treatment policy. Once the diagnosis is confirmed by genetic testing, ATRA-based induction therapy can be initiated. This is also applicable in atypical cases such as the M3 variant. Furthermore, after ATRA-based induction therapy, the curative effect is evaluated by quantitative PCR analysis. Thus, genetic testing is important in the follow-up of patients with APL. [Review].

[The Present State of Inter-Laboratory Differences in Setting and Practicing Critical Values -Results of a Questionnaire Survey Performed to the Laboratories of Keio University-Associated Hospitals].

Ito M, Kano S, Nakagawa T … +11 more , Kikuchi H, Shibata A, Ota A, Hayakawa T, Ogawa H, Tani A, Takeda H, Koyama H, Ishibashi M, Yamalzaki K, Murata M

Rinsho Byori · 2017 Jan · PMID 30695509

Presently we, Keio Endocrine and Metabolite Survey (KEMS) study group conducted a questionnaire sur- vey with respect to panic values in the laboratories belonging to Keio University-associated hospitals. As to the initi... Presently we, Keio Endocrine and Metabolite Survey (KEMS) study group conducted a questionnaire sur- vey with respect to panic values in the laboratories belonging to Keio University-associated hospitals. As to the initial setting, most of the laboratories answered to play a leading role in preparing the necessary matters to implementation of panic values and revise them corresponding to physician's request on each occasion. In almost all laboratories, they did not verify whether the notification procedure does work to exert appropriate clinical action. The numbers of critical values answered by the 18 laboratories distributed widely in the test items (8-39) and their critical limits (10-68). As to the critical limits, the lower limits of serum K and blood glucose converged among the laboratories, however, the limits of other test items diverged. The results of the present survey regarding to critical values, although being in small scale, may submit the im- portant issue to be solved in near future. [Short Communication].

[Validation of Whole Slide Imaging for Primary Diagnosis of Gastrointestinal Pathology].

Yoshizawa A, Tanaka M

Rinsho Byori · 2017 Jan · PMID 30695508

Whole-slide imaging (WSI) technology enables the primary diagnosis of histopathological slides. This study aimed to determine the diagnostic concordance between pathological interpretations made using WSI and those made... Whole-slide imaging (WSI) technology enables the primary diagnosis of histopathological slides. This study aimed to determine the diagnostic concordance between pathological interpretations made using WSI and those made using light microscopy (LM). For this study, 5,704 consecutive surgical pathological cases from a community hospital were included. The specimens were digitized at x40 magnification for biopsy and endoscopic resection specimens or at x20 magnification for other specimens and evaluated by 11 pathologists for diagnosis using WSI. Subsequently, the specimens were signed out using LM by 3 pathologists after 2 weeks. Diagnoses using WSI were then compared with the diagnoses made by using LM. Most (96.8%) of the 5,704 specimens were obtained from the gastrointestinal tract (2,441 biopsy specimens from the esophagogastroduodenum [42.7%], 1,678 endoscopic resection specimens from the colorectum [29.4%], 1,349 biopsy specimens from the colorectum [23.6%], 133 resected specimens from the gallbladder [2.3%], 56 endoscopic resection specimens from the stomach [0.9%], 30 resected specimens from the ap- pendix [0.5%], 14 skin biopsy specimens [0.2%], and 3 other specimens [0.1%]). The overall concordance between the diagnoses made using WSI and those made using LM was 95.1%. The major and minor dis- crepancy rates for WSI were 0.1% and 4.8%, respectively. None of the discordant cases had any clinical or prognostic implications. In conclusion, this study revealed that WSI can be used for primary diagnosis of gastrointestinal biopsy and endoscopic resection specimens. To the best of our knowledge, this is one of the studies that clearly proved that diagnosis using WSI is equivalent to diagnosis using LM. [Original].

[Evaluation of a Newly Developed Reagent "Lias Auto P-FDP" on Coapresta 2000 and Clinico-Pathological Analysis of Discrepant Samples in FDP Value].

Kondo M, Tamura T, Miura H … +1 more , Sato A

Rinsho Byori · 2017 Jan · PMID 30695507

Patients with disseminated intravascular coagulation (DIC) exhibit increased levels of fibrin/fibrinogen degradation products (FDP), and FDP levels are carefully monitored as a marker of fibrinolysis during the diagnosis... Patients with disseminated intravascular coagulation (DIC) exhibit increased levels of fibrin/fibrinogen degradation products (FDP), and FDP levels are carefully monitored as a marker of fibrinolysis during the diagnosis of DIC and other fibrinolysis-related conditions. Although FDP levels can be measured using automatic analyzers, it is reported that measured FDP values differ depending on the reagent used. Recently, a newly developed reagent for measuring FDP levels (Lias Auto P-FDP) was launched. In this study, we used Lias Auto P-FDP in combination with the Coapresta 2000 automatic analyzer and evaluated its reactivity. We confirmed the reproducibility of the measurements obtained with the Lias Auto P-FDP reagent when the manufacturer's instructions were followed and that the Lias Auto P-FDP reagent can be used with the Coapresta 2000. In the reactivity test, the Lias Auto P-FDP reagent exhibited stronger reactivity with low molecular weight FDP than the reagent we currently use (BL2 P-FDP). Moreover, the samples that exhibited non-specific reactions to the BL2 P-FDP reagent did not display similar reactions to the Lias auto P-FDP reagent. In the clinico-pathological analysis of divergent value between Lias Auto P-FDP and BL2 P-FDP, seven cases were highly discrepant value of FDP. Interestingly, we found the description of pleural fluid and/or ascites in 85.7% cases. In conclusion, we confirmed that the Lias Auto P-FDP reagent can be used in combination with the Coapresta 2000. In addition, the reactivity of FDP varied depending on the reagent used. It is important to understand the characteristics of each FDP reagent and which automatic analyzers they can be used with. [Original].

[IgM Antibody against IgG Antibody Binding to Antigen, So-Called Anti-Antibody, Reacts Mainly with F (ab')₂ Fragment Possessing Antibody Activity].

Matsuura T, Imamura A, Ota T

Rinsho Byori · 2017 Jan · PMID 30695506

OBJECTIVE: To develop enzyme-linked immunosorbent assay (ELISA) for measurement of IgM antibody (anti-antibody) against human IgG antibody that is binding to antigen, to distinguish anti-antibody from other antiglobulins... OBJECTIVE: To develop enzyme-linked immunosorbent assay (ELISA) for measurement of IgM antibody (anti-antibody) against human IgG antibody that is binding to antigen, to distinguish anti-antibody from other antiglobulins, e.g. rheumatoid factor (RF), and to search their localization of epitope on IgG molecule. METHODS: We chose purified human IgG anti-dsDNA antibody from a patient with systemic lupus erythematosus as IgG antibody and calf thymus dsDNA as antigen. IgG F (ab')₂ fragment was obtained by digestion of the IgG with pepsin. Those IgG and IgG F (ab') 2 with anti-dsDNA antibody were reacted with pre-coated dsDNA and formed immune complex on ELISA plate. On the other hand we prepared ELISA plate on which those IgG and IgG F (ab') 2 were coated directly for measurement of IgM RF and IgM antihinge antibody. Twenty-three sera from patients with rheumatoid arthritis were tested. RESULTS: Correct IgM anti-antibodies were obtained after subtraction of absorbance of IgM anti-dsDNA anti- bodies. Remarkable correlation between IgM anti-antibodies obtained by using whole IgG and those by using IgG F(ab')₂(n=23, r²=0.914, p=1.11X10-12). There were correlations neither between IgM antiantibodies and IgM RF(n=23, r²=0.001, p=0.889) nor between IgM antiantibodies and IgM antihinge antibodies (n=23, r²=0.063, p=0.249). CONCLUSIONS: IgM molecule with anti-antibody specificity seems to be different from IgM RF and IgM antihinge antibody. Moreover, epitope recognized by IgM anti-antibody seems to localize on IgG F (ab') 2 but not on hinge region. [Original].

[Efficacy of Human Immunodeficiency Virus (HIV) Antigen-Antibody Combination Assay as a Screening Test and Factors Causing False-Positivity].

Inoue T, Goto T, Ogiwara T … +7 more , Oohashi M, Ohike T, Kani S, Shinkai N, Wakimoto Y, Sato S, Tanaka Y

Rinsho Byori · 2016 Dec · PMID 30676009

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... 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]

[Therapeutic Drug Monitoring of Antiarrhythmic Drugs].

Takahashi N

Rinsho Byori · 2016 Dec · PMID 30653903

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... 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].

[Therapeutic Drug Monitoring of Immunosuppressive Drugs].

Satoh S, Miura M

Rinsho Byori · 2016 Dec · PMID 30653902

Calcineurin inhibitors, cyclosporine and tacrolimus, and everolimus are used to prevent reactions following organ transplantation. However, these immunosuppressive drugs have narrow therapeutic ranges, and their inter- a... Calcineurin inhibitors, cyclosporine and tacrolimus, and everolimus are used to prevent reactions following organ transplantation. However, these immunosuppressive drugs have narrow therapeutic ranges, and their inter- and intra-individual pharmacokinetics differ greatly. Therefore, daily doses must be adjusted accord- ing to blood trough concentrations. Although mycophenolate mofetil is generally used in a fixed dosing strategy, the need for more accurate drug dosing has become evident. A number of clinical factors, such as the time from transplantation, patient age and ethnicity, food consump- tion, albumin and hematocrit values, liver function, gastrointestinal motility, concomitant medication, and genetics, may affect the pharmacokinetics of immunosuppressive agents. The Japanese Society of Therapeutic Drug Monitoring (JSTDM) and the Japanese Society of Transplantation (JST) have developed and launched the first TDM guidelines to standardize routine TDM practice for immu- nosuppressive drugs used in kidney, liver and heart transplantation. These guidelines describe a consensus document among transplantation experts of the JST and TDM experts of the JSTDM. In the main part of this document, the TDM guidelines for immunosuppressive drugs are summarized and described. [Review].

[Monitoring of the Blood Concentrations of Antiepileptic Drugs (TDM)].

Kawasaki Y, Sendo T

Rinsho Byori · 2016 Dec · PMID 30653901

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 seiz... 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].

[Therapeutic Drug Monitoring of Antimicrobial Agents].

Kadomura S

Rinsho Byori · 2016 Dec · PMID 30653900

Antimicrobial dosing can be targeted to achieve pharmacokinetic (PK) -pharmacodynamic parameters at the minimal inhibitory concentration of bacteria. Therapeutic drug monitoring (TDM) of glycopetides [vanco- mycin (VCM)... Antimicrobial dosing can be targeted to achieve pharmacokinetic (PK) -pharmacodynamic parameters at the minimal inhibitory concentration of bacteria. Therapeutic drug monitoring (TDM) of glycopetides [vanco- mycin (VCM) and teicoplanin] and aminoglycosides (gentamicin, tobramycin, and amikacin) makes it possible to optimize dosing in individual patients. TDM of these antimicrobials can improve clinical outcomes, de- crease adverse events, and reduce costs. Therefore, PK-monitoring for VCM and aminoglycosides is rec- ommended in the Antimicrobial Stewardship Program implementing guidelines developed by the Infectious Disease Society of America and the Society for Healthcare Epidemiology of America in 2016. In addition, Clinical practice guidelines for TDM have been developed by the Japanese Society of Chemotherapy and the Japanese Society of TDM since 2012, and they were updated in 2016. The aim of this study was to review TDM of antimicrobial agents. [Review].

[Clinical Application of Immunosuppressive Factors in Cancer Diagnosis and Therapy].

Ito H

Rinsho Byori · 2016 Dec · PMID 30653899

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, antib... 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].

[The Unit Use Situation and Problems of the Examination of Blood Count in Fukushima].

Tanaka K, Hashimoto S, Hosoya M … +1 more , Yasumura S

Rinsho Byori · 2016 Dec · PMID 30653898

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 Re... 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].

[An Abnormal Alpha-Fetoprotein Fractionation Provides Additional Information: A Case of Retroperitoneal Germ Cell Tumor Accompanied by Liver Cirrhosis Type C].

Aihara M, Gotoh K, Maruyama K … +6 more , Yamanaka M, Sakemoto M, Suzuki H, Kato M, Hotta T, Kang D

Rinsho Byori · 2016 Dec · PMID 30653897

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, me... 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].

Performance Evaluation of a Novel Fully Automated Real-Time Reverse Transcriptase-Polymerase Chain Reaction Kit for the Detection of Norovirus.

Hosoda T, Uehara Y, Matsuda N … +7 more , Kawase' Y, Tanei M, Haba Y, Nakamura A, Tabe Y, Naito T, Ohsaka A

Rinsho Byori · 2016 Dec · PMID 30653896

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 chai... 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].

[Investigation of the Renal Function Evaluation in the Living Donor Renal Transplantation Candidate at Our Center].

Kozaki K

Rinsho Byori · 2016 Dec · PMID 30653895

In Japan, the number of living renal transplant donors with medical complications has been increasing in recent years due to the.aging of donors. It is important to assess donor renal function properly before donation to... In Japan, the number of living renal transplant donors with medical complications has been increasing in recent years due to the.aging of donors. It is important to assess donor renal function properly before donation to ensure donor safety. This study aimed to assess different renal function measures of donors, includ- ing serum creatinine (Cr), creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR), and inulin clearance (Cin). The mean Cr and eGFR values of 64 donors before surgery and at 1 month, 1 year, and 3 years after surgery were 0.74, 1.15, 1.13, and 1.05 mg/dL, respectively, and 71.7, 42.4, 44.9, and 49.5 mL/min/1.73m2, respectively. Values of eGFR 3 years after surgery in 20 out of 36 donors (55.6%) were less than 50 mL/min/1.73m2, showing that moderately decreased levels of GFR persist for a long time after donation. The preoperative renal function of 20 candidate donors was evaluated based on Cr, Ccr, eGFR, and Cin. The mean preoperative values were Cr 0.74 mg/dL, eGFR 71.9 mL/min/1.73m2, Ccr 137.3 mL/min, and Cin 92.9 mL/min. Ccr overestimated Cin in 18 out of 20 donors (90%) and eGFR underestimated Cin in 16 donors (80%). Cin measurements are complicated, which can lead to human errors in measurement. Conversely, eGFR measurements are simple but are inferior to Cin in terms of accuracy; therefore, the pre- operative renal function of donors should be evaluated by Cin, combined with other tests as much as possible to ensure a safe living renal transplant. [Original].

[Case Conference of Hematological Malignancies Based on the Morphology of Blood Cells: Chairmen's Introductory Remarks].

Inaba T, Ikemoto T

Rinsho Byori · 2016 Nov · PMID 30695313

A case conference of hematological malignancies based on the morphology of blood cells was held as a Joint Symposium of the Japanese Society of Laboratory Medicine and Japanese Society of Laboratory Hematology. This styl... A case conference of hematological malignancies based on the morphology of blood cells was held as a Joint Symposium of the Japanese Society of Laboratory Medicine and Japanese Society of Laboratory Hematology. This style of joint symposium was held four times from 2012 to 2016, whereas child cases were presented for the first time this year. The 4 cases presented in this symposium were as follows: an infant with Down syn- drome showing an atypical clinical course of transient abnormal myelopoiesis (TAM) and myeloid leukemia, a relatively older girl with juvenile myelomonocytic leukemia (JMML), one adult with acute myeloid leukemia (AML) with inv (16) (p13.1q22); CBFB-MYH11 morphologically resembling AML with t (8;21) (q22;q22.1); RUNX1-RUNX1T1, and one adult with high-grade B-cell lymphoma showing t (14;18) (q32;q21); IGH/BCL2. Each case included pathological and interesting morphological findings that were carefully examined and in- tensively discussed by two experienced commentators and participants, including pediatric hemato- pathologists. The importance of the morphological evaluation of characteristic cells such as immature leukemic blasts or lymphomatous ones was reconfirmed at this conference. In addition, immunological, cytogenetic, and molecular examinations were also essential for the final diagnosis of these cases. [Review].

Potential of Theranostic Target Mining in the Development of Novel Diagnostic and Therapeutic Products in Oncology: Progranulin/GP88 as a Therapeutic and Diagnostic Target for Breast and Lung Cancers.

Serrero G

Rinsho Byori · 2016 Nov · PMID 30695312

Biological therapy with companion diagnostic such as the combination of anti-Her-2 therapy (Herceptin™) and measurement of Her-2 expression in breast tumors (HercepTest™) has proven successful in Oncology. Screening targ... Biological therapy with companion diagnostic such as the combination of anti-Her-2 therapy (Herceptin™) and measurement of Her-2 expression in breast tumors (HercepTest™) has proven successful in Oncology. Screening targets that have both diagnostic and therapeutic applications (theranostic targets) at the discovery stage should provide the best strategy for the development of novel targeted therapies with companion diag- nostics in Oncology. This strategy is at the basis of the product pipeline developed by A&G Pharmaceutical. To identify theranostic targets, A&G has developed a biological screen for functional drivers of tumorigenesis abnormally expressed in cancer tissues when compared to normal tissue counterparts. The advantage of this strategy is that identified targets will combine from the start, diagnostic and therapeutic applications. A&G has identified a secreted 88 kDa autocrine growth and survival factor, GP88 (progranulin) overex- pressed in cancer tissue and has demonstrated its critical role in the biological process of breast cancer devel- opment, invasiveness, survival and drug resistance. A protein/antibody-based pipeline consisting of prod- ucts able to detect GP88 in tissues, in circulation and to block GP88 was developed at A&G. This pipeline combines a neutralizing anti-GP88 monoclonal antibody therapeutic with two companion diagnostic tissue (IHC) and serum (EIA) tests. Diagnostic kits for measurement of GP88 in tissue and serum of cancer pa- tients have been validated in clinical studies. Preclinical and pathological studies support the importance of diagnostic and therapeutic products and the potential of GP88 targeted therapy with companion diagnostic in the clinical settings for several cancer indications such as anti-estrogen resistant breast cancer. [Review].
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