False-positive Elevations in Carcinoembryonic Antigen Levels at a Health Screening Center

BACKGROUND: Although routine screening of carcinoembryonic antigen (CEA) is not recommended for the early diagnosis of colorectal cancers, CEA levels are frequently measured in practice and during opportunistic health screening programs. We evaluated the frequency of false-positive results according to CEA level at a health screening center. METHODS: The medical records of 25,786 participants who underwent a general health check-up and CEA testing at the Seoul National University Hospital Healthcare System Gangnam Center from March 2015 to February 2016 were reviewed. CEA levels were measured using the Architect i2000sr (Abbott Laboratories, USA). The cut-off level for elevated CEA was 5.0 ng/mL. RESULTS: Among 25,786 participants who underwent CEA screening, 597 (2.3%) had CEA levels >5.0 ng/mL. Among 597 participants with elevated CEA levels, 12 (2.0%) had actual malignancies with CEA levels of 8.3–155.3 ng/mL. Diabetes, smoking, chronic obstructive pulmonary disease, and colonic polyps were considered as causes of false elevation. The false-positive rates of CEA according to level were as follows: 5.1–10.0 ng/mL, 99.5%; 10.1–15.0 ng/mL, 87.2%; 15.1–20.0 ng/mL, 100.0%; >20.0 ng/mL, 33.3%. A subsequent decrease in the CEA level after a 1-month follow-up was observed in 47.6% of all cases with elevated CEA levels. CONCLUSIONS: False elevation in CEA levels in the range of 5.0–20.0 ng/mL is common in patients who underwent testing at a health screening center. False-positive results above 20.0 ng/mL are less common. These data could provide a guide for the interpretation of elevated CEA level at a health screening center.

Six Years' Experience of Accuracy-Based Proficiency Testing for HbA1c in Korea

BACKGROUND: The proficiency testing (PT) program for HbA1c, performed by the Korean Association of External Quality Assessment Service (KAEQAS), first started in 2007. From 2007 to 2008, the results were assessed using means as the standard within a peer group (identical method group). However, the assessment method changed to accuracy-based PT in 2009. This study aimed to analyse the results of an external quality assessment of HbA1c from 2009 to 2014. METHODS: Based on the data obtained from the external quality assessment of HbA1c from 2009 to 2014, we analysed the number of participating institutions, response rate, 'unacceptable' result rate, bias from the target value, and CVs according to each instrument code. RESULTS: The number of participating institutions was only 180 in 2009. However, it increased over the next 5 years, and as of 2014, 345 institutions were enrolled. The response rates were 93.8% to 99.1%. Since 2009, the measurement method changed and most of the participating institutions now use the high-performance liquid chromatography (HPLC) method. As of 2014, the HPLC method showed small bias from the target value and inter-laboratory CVs (<3.5%), demonstrating satisfactory performance. Immunoassays and point-of-care testing (POCT) demonstrated relatively unsatisfactory performance, showing larger inter-laboratory CVs compared to those obtained with the HPLC method, with some of them exceeding the acceptance limit of +/-8% of the target value. CONCLUSIONS: As of 2014, relatively large-scale laboratories are participating in the accuracy-based PT for HbA1c. According to the accuracy-based PT for HbA1c, POCT showed the highest 'unacceptable' rate and imprecision. Therefore, small-scale laboratories mostly using POCT for HbA1c measurement should be encouraged to participate in the accuracy-based PT program for HbA1c, and the external quality assessment program undertaken by KAEQAS should be expanded.

Prevalence and Genotype of Human Papillomavirus Infection and Risk of Cervical Dysplasia among Asymptomatic Korean Women / 대한임상미생물학회지

BACKGROUND: The persistence of infection by high-risk human papillomavirus (HPV) may lead to cervical cancer. Recently, the American Society for Colposcopy and Cervical Pathology (ASCCP) announced that oncogenic HPV screening and the PAP smear are the main methods of screening for cervical cancer. The goal of this study was to investigate the prevalence and genotyping of HPV, as well as the risk of cervical dysplasia. METHODS: HPV genotyping was conducted by a commercial chip assay. Cervical dysplasia was retrospectively reviewed using electronic medical records. The study participants were grouped together according to cervical dysplasia status: 'no dysplasia,' 'atypical squamous cells of undetermined significance (ASCUS),' 'low-grade squamous intraepithelial lesion (LSIL),' and 'high-grade squamous intraepithelial lesion (HSIL).' The HPV prevalence and genotyping were analyzed according to the cervical dysplasia group. RESULTS: The overall prevalence of HPV was 17.6% (91 out of 518 patients). HPV-18 (2.3%), HPV-16 (2.1%), and HPV-58 (1.2%) were the three most frequent genotypes. The prevalence of HPV infection and the high-risk HPV positive rate was higher in the ASCUS, LSIL, and HSIL groups than in the no dysplasia group (P<0.05). CONCLUSION: In this study, basic data regarding the prevalence and distribution of HPV genotypes were obtained. Since HPV vaccination has been actively encouraged among Korean women, a change in the prevalence of HPV and cervical dysplasia is expected in the future. This study provided basic data describing the prevalence of HPV and its genotypes in the pre-HPV vaccination era.

Comparison of Modified Multiple-locus Variable-number Tandem-repeat Fingerprinting with Pulsed-field Gel Electrophoresis for Typing Clinical Isolates of Staphylococcus aureus

BACKGROUND: Multiple-locus variable-number tandem-repeat fingerprinting (MLVF) is based on multiplex PCR, utilizing variable number tandem repeat. Our goal was to compare the performance of MLVF in distinguishing clinical Staphylococcus aureus isolates with that of pulsed-field gel electrophoresis (PFGE), which has traditionally been the gold standard. METHODS: Sixty-three clinically significant S. aureus isolates were tested using both PFGE and MLVF. Multiplex PCR for MLVF was performed using PCR primers for clfA, clfB, sdrCDE, sspA, and spa. PFGE was performed with genomic DNA fragments generated by SmaI endonuclease digestion. Banding patterns of MLVF or PFGE were analyzed using InfoQuestFP software. RESULTS: The hands-on time of our modified method was about 3 h, on average, for each of 18 isolates. PFGE (80% cutoff) or MLVF (75% cutoff) separated all of the 63 isolates into 13 and 12 types, respectively. Three types generated by PFGE were identical to those generated by MLVF. PFGE and MLVF yielded similar Simpson's diversity indices, indicating similar discriminatory power. The overall concordance between PFGE and MLVF was low, as represented by adjusted Rand indices (0.266-0.278). PFGE predicted MLVF type better than MLVF predicted PFGE type, as reflected by Wallace coefficients (PFGE cutoff 80% vs. MLVF cutoff 75%, 0.389 vs. 0.233). Analysis of the relationship between a pair of isolates showed 91.0% concordance between the PFGE (80% cutoff) and MLVF (75% cutoff). CONCLUSIONS: Our simple, low-cost, modified MLVF protocol can effectively discriminate between S. aureus clinical isolates. MLVF can replace PFGE for the hospital infection control of S. aureus.

A Case of Good's Syndrome with Weak ABO Reverse Type / 대한수혈학회지

Good's syndrome (thymoma with immunodeficiency) is a rare cause of combined B-cell and T-cell immunodeficiency in adults. We present here a case of Good's syndrome involving a 52 year-old man with an ABO blood group abnormality. He had undergone surgery for thymoma with myasthenia gravis 27 years ago. He also had a history of pulmonary tuberculosis, herpes zoster and pure red cell aplasia. On admission, he was suspected of having pneumonia, and S. pneumoniae was isolated from blood culture. The immunoglobulin levels were markedly decreased. Lymphocyte subset analysis revealed the absence of CD19+ B cells. The result of ABO typing showed a normal strong reaction on the cell typing, but a relatively weak reaction on the serum typing. Therefore, we performed ABO genotyping to confirm his ABO type, which was revealed to be B/O1 . This case suggests that ABO typing should be performed when the diagnosis of Good's syndrome is made. Moreover, Good's syndrome (thymoma with hypogammaglobulinemia) should be considered and evaluated for in patients with a weak ABO reverse type.

A Case of Brain Abscess Caused by Propionibacterium acnes 13 Months after Neurosurgery and Confirmed by 16S rRNA Gene Sequencing / 대한진단검사의학회지

Propionibacterium acnes is a gram-positive anaerobic bacillus and a normal inhabitant of the skin. Although it is often considered a contaminant of blood cultures, it can occasionally cause serious infections, including postoperative central nervous system infections. Here, we report the case of a 70-yr-old man who developed a large cerebral abscess caused by P. acnes 13 months after neurosurgery. Immediate gram staining of the pus from his brain revealed the presence of gram-positive coccobacilli. However, colony growth was observed only after 5 days of culture. Therefore, we performed 16S rRNA gene sequencing of the pus specimen. The isolate was identified as P. acnes. The colonies developed 9 days after the initial culture. The API Rapid ID 32A test (bioMerieux, France) was performed using a colony, but an unacceptable profile was obtained. Then, the pus was transferred into the enrichment broths of the BACTEC FX (Becton Dickinson, USA) and BacT/Alert 3D (bioMerieux, Organon Teknika, USA) systems, but only the BACTEC FX system could detect growth after 5 days. We performed 16S rRNA gene sequencing and API Rapid 32A profiling with a colony recovered from Brucella agar, which was inoculated with the microbial growth in the enrichment broth from the BACTEC FX system. The organism was identified as P. acnes by both methods. This case suggests that 16S rRNA gene sequencing may be a useful alternative for identifying slowly growing P. acnes from specimens that do not show growth after 5 days of culture.

Clathrin Assembly Lymphoid Myeloid Leukemia-AF10-positive Acute Leukemias: A Report of 2 Cases with a Review of the Literature / 대한진단검사의학회지

The translocation t(10;11)(p13;q14q21) has been found to be recurrent in acute lymphoblastic and myeloid leukemias, and results in the fusion of the clathrin assembly lymphoid myeloid leukemia (CALM) gene with the AF10 gene; these genes are present on chromosomes 11 and 10, respectively. Because the CALM-AF10 rearrangement is a rare chromosomal abnormality, it is not included in routine molecular tests for acute leukemia. Here, we describe the cases of 2 patients with the CALM-AF10 fusion gene. The first patient (case 1) was diagnosed with T-cell ALL, and the second patient (case 2) was diagnosed with AML. Both patient samples showed expression of the homeobox A gene cluster and the histone methyltransferase hDOT1L, which suggests that they mediate leukemic transformation in CALM-AF10-positive and mixed-lineage leukemia-AF10-positive leukemias. Both patients achieved complete remission after induction chemotherapy. The first patient (case 1) relapsed after double-unit cord blood transplantation; there was no evidence of relapse in the second patient (case 2) after allogenic peripheral blood stem cell transplantation. Since CALM-AF10- positive leukemias have been shown to have poor prognosis with conventional therapy, molecular tests for CALM-AF10 rearrangement would be necessary to detect minimal residual disease during follow-up.