Prevalence of BRAF(V600E) Mutation in Follicular Variant of Papillary Thyroid Carcinoma and Non-Invasive Follicular Tumor with Papillary-Like Nuclear Features (NIFTP) in a BRAF(V600E) Prevalent Area

BACKGROUND: BRAF V600E mutation status and prevalence of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been reported in Korea. The aim of this study was to investigate the significance of the BRAF V600E mutation in the follicular variant of papillary thyroid carcinoma (FVPTC) and to determine the prevalence of NIFTP in BRAF V600E mutation-prevalent Korean patients. METHODS: This study retrospectively analyzed 1,417 consecutive patients who underwent total thyroidectomy with routine prophylactic central lymph node dissection for papillary thyroid carcinoma (PTC). BRAF V600E mutation analysis was performed routinely using multiplex polymerase chain reaction by applying dual priming oligonucleotide. Clinicopathological characteristics and ultrasonographic findings were compared between BRAF V600E mutation-positive and -negative groups for FVPTC. Pathologists reviewed the pathology slides according to consensus diagnostic criteria for the encapsulated FVPTC and NIFTP. RESULTS: The prevalence of the BRAF V600E mutation in all subtypes of PTC was 61.0% (861/1,411). FVPTC presented a BRAF V600E mutation rate of 27.3%. The FVPTC patients with BRAF V600E mutation were older than those with no BRAF V600E mutation (P = 0.021). The prevalence of NIFTP was 0.18% among all PTC patients (2/1,411) and the proportion of NIFTP among FVPTC was 9.1% (2/22). CONCLUSION: The BRAF V600E mutation is prevalent in Korean patients with FVPTC in a region with high frequency of the BRAF V600E mutation and very low prevalence of NIFTP compared with that reported in western studies.

The Effectiveness of Multidisciplinary Team-Based Education in the Management of Type 2 Diabetes / 임상당뇨병

BACKGROUND: Although clinicians, nurse specialists, pharmacists, and nutritionists expend significant time and resources in optimizing care for patients with diabetes, the effectiveness of integrated diabetes care team approach remains unclear. We assessed the effects of a multidisciplinary team care educational intervention on glycated hemoglobin (HbA1c) levels among diabetes patients. METHODS: We conducted a matched case-control study in Korean patients with type 2 diabetes, comparing the propensity scores pertaining to the effectiveness in reducing HbA1c levels between a group receiving an educational intervention and a control group. We included 40 pairs of patients hospitalized between June 2014 and September 2016. HbA1c values measured at baseline, 3 months, and 6 months were compared between the two groups. RESULTS: The educated group showed an improvement in HbA1c levels compared to the control group at 3 months (6.3 ± 2.3% vs. 9.5 ± 4.0%; P = 0.020) and at 6 months (7.5 ± 1.5% vs. 9.6 ± 3.0%; P = 0.106). There was a significant difference in the change in mean HbA1c from baseline to 3 months between the two groups (−35.7 ± 26.1% vs. −9.1 ± 20.5%; P = 0.013). CONCLUSION: A multidisciplinary team care education intervention was advantageous for improving glucose control in patients with type 2 diabetes, and may help to optimize glycemic control in clinical practice.

Comparison of Analytical and Clinical Performance of HPV 9G DNA Chip, PANArray HPV Genotyping Chip, and Hybrid-Capture II Assay in Cervicovaginal Swabs

BACKGROUND: Human papillomavirus (HPV) infection can be detected by using several molecular methods, including Hybrid-Capture II (HC2) assay and variable HPV DNA chip tests, although each method has different sensitivities and specificities. METHODS: We performed HPV 9G DNA Chip (9G) and PANArray HPV Genotyping Chip (PANArray) tests on 118 cervicovaginal swabs and compared the results with HC2, cytology, histology, and direct sequencing results. RESULTS: The overall and high-risk HPV (HR-HPV) positivity rates were 62.7% and 44.9% using 9G, and 61.0% and 30.5% using PANArray, respectively. The positivity rates for HR-HPV with these two chips were significantly lower than 55.1% when HC2 was used. The sensitivity of overall HPV positivity in detecting histologically confirmed low-grade cervical squamous intraepithelial lesions or higher was 88.7% for all three tests. The specificity was 58.5% for 9G and 61.5% for PANArray, which was significantly lower than the 72.3% for HC2. With the HR-HPV+ genotype threshold, the sensitivity decreased to 75.5% for 9G and 52.8% for PANArray, which was significantly lower than the 88.7% for HC2. Comparison of the two chips showed concordant results in 55.1% of the samples, compatible results in 16.9%, and discordant results in 28.0%, exhibiting poor agreement in detecting  certain HPV genotypes. Compared with direct sequencing, 9G yielded no discordant results, whereas PANArray yielded 31 discordant results (26.7%). CONCLUSIONS: Compared with HC2, the HPV genotyping tests showed lower sensitivity in histologic correlation. When the two chips were compared, the 9G was more sensitive and accurate for detecting HR-HPV than the PANArray.

Detection of EGFR and KRAS Mutation by Pyrosequencing Analysis in Cytologic Samples of Non-Small Cell Lung Cancer

EGFR and KRAS mutations are two of the most common mutations that are present in lung cancer. Screening and detecting these mutations are of issue these days, and many different methods and tissue samples are currently used to effectively detect these two mutations. In this study, we aimed to evaluate the testing for EGFR and KRAS mutations by pyrosequencing method, and compared the yield of cytology versus histology specimens in a consecutive series of patients with lung cancer. We retrospectively reviewed EGFR and KRAS mutation results of 399 (patients with EGFR mutation test) and 323 patients (patients with KRAS mutation test) diagnosed with lung cancer in Konkuk University Medical Center from 2008 to 2014. Among them, 60 patients had received both EGFR and KRAS mutation studies. We compared the detection rate of EGFR and KRAS tests in cytology, biopsy, and resection specimens. EGFR and KRAS mutations were detected in 29.8% and 8.7% of total patients, and the positive mutation results of EGFR and KRAS were mutually exclusive. The detection rate of EGFR mutation in cytology was higher than non-cytology (biopsy or resection) materials (cytology: 48.5%, non-cytology: 26.1%), and the detection rate of KRAS mutation in cytology specimens was comparable to non-cytology specimens (cytology: 8.3%, non-cytology: 8.7%). We suggest that cytology specimens are good alternatives that can readily substitute tissue samples for testing both EGFR and KRAS mutations. Moreover, pyrosequencing method is highly sensitive in detecting EGFR and KRAS mutations in lung cancer patients.

The Natural Course of Endobronchial Inflammatory Polyps as a Complication after Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration / 결핵및호흡기질환

We presented a case of unusual endobronchial inflammatory polyps as a complication following endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in a patient with tuberculous lymphadenitis. EBUS-TBNA of the right hilar lymph node was performed in a 29-year-old, previously healthy man. The patient was confirmed with tuberculous lymphadenitis and received antituberculosis medication over the course of 6 months. Chest computed tomography, after 6 months of antituberculosis therapy following the EBUS-TBNA showed nodular bronchial wall thickening of the right main bronchus. Histological and microbiological examinations revealed inflammatory polyps. After 7 months, the inflammatory polyps regressed almost completely without need for removal.

A Case of Multifocal Papillary Thyroid Carcinoma Consisting of One Encapsulated Follicular Variant with BRAF K601E Mutation and Three Conventional Types with BRAF V600E Mutation

Multifocal papillary thyroid carcinoma (mPTC) comprises about 20-30% of PTC. In mPTC, individual tumor foci can be identical or frequently composed of different histological types including follicular, solid, tall-cell or conventional patterns. We report a case of mPTC consisting of one encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) and three conventional PTCs in a 44-year-old woman. This case genetically demonstrates unique features including the simultaneous presence of the BRAF V600E (T1799A) mutation and the BRAF K601E (A1801G) mutation in conventional PTC and FVPTC, respectively.

Clinical Usefulness of SurePath(TM) Liquid-based Cytology in Thyroid Fine Needle Aspiration: Comparison with the Conventional Smear in Diagnostic Efficacy and Applicability of BRAF Mutation Test

BACKGROUND: Recently, liquid-based cytology (LBC) has been introduced as an alternative to the conventional smear (CS) technique in thyroid fine needle aspiration, due to its diagnostic convenience. METHODS: We assessed 77 cases of thyroid fine needle aspiration using the SurePath(TM) method (SP) as LBC and CS via split-sample techniques. BRAF mutation tests were carried out via polymerase chain reaction and pyrosequencing immediately after diagnosis or a delay of more than one year. RESULTS: In a comparison between SP and CS, the rate of concordance between SP and CS was as high as 84.4% (kappa value, 0.754). In comparison with histologic diagnosis, the overall sensitivity was 100% for both. The specificity was 62.5% for SP and 56.3% for CS. Relative to CS, papillary carcinomas on SP slides revealed more accentuated nuclear irregularities, nucleoli, and reduced nuclear size. In contrast to CS, the delayed BRAFV600E mutation test using SP slides after 1-2 years failed. The use of new primers amplifying shorter product size could help the delayed test achieve success. CONCLUSIONS: Differences in the diagnostic efficacy of SP and CS were negligible. The failure of the delayed BRAF mutation test on the SP slides might be associated with DNA degradation.

PNA-Mediated PCR Clamping for the Detection of EGFR Mutations in Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Recent studies have demonstrated that the epidermal growth factor receptor (EGFR) genotype is the most important predictive marker to EGFR-tyrosine kinase inhibitors (TKIs) and first-line gefitinib treatment will be approved in the near future for use in non-small cell lung cancer (NSCLC) patients with the EGFR mutation. Direct sequencing is known to be the standard for detecting EGFR mutations; however, it has limited sensitivity. Peptide nucleic acids (PNA)-mediated PCR clamping method is a newly introduced method for analyzing EGFR mutations with increased sensitivity and stability. METHODS: A total of 71 NSCLC patients were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. Sixty-nine patients were analyzed for clinicopathologic correlation with EGFR genotype; 2 patients with indeterminate results were excluded. In order to determine EGFR-TKI drug response, 57 patients (42 gefitinib, 15 erlotinib) were included in the analysis. RESULTS: The EGFR mutation rate was 47.8%. Being female, a non-smoker, and having adenocarcinoma were favorable clinicopathologic factors, as expected. However, more than a few smokers (33.3%), male (28.1%), and patients with non-adenocarcinoma (28.6%) had the EGFR mutation. Having a combination of favorable clinicopathologic factors did not increase the EGFR mutation rate significantly. Drug response to EGFR-TKIs showed significant differences depending on the EGFR genotype; ORR was 14.3% for wild type vs 69.0% for mutant type; DCR is 28.6% for wild type vs 96.6% for mutant type. The median EGFR-TKI treatment duration is 7.6 months for mutant type group and 1.4 months for wild type group. CONCLUSION: EGFR genotype determined using the PNA-mediated PCR clamping method is significantly correlated with the clinical EGFR-TKI responses and PNA-mediated PCR.