Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Biopsy ; Carcinoma, Non-Small-Cell Lung ; DNA ; Genes, erbB-1 ; Humans ; Insurance ; Lung Neoplasms ; Lung ; Methods ; Pathology ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

BACKGROUND AND OBJECTIVES: There has been no nation-wide data on the outcomes of transcatheter aortic valve implantation (TAVI) after commercialization of TAVI in Korea. We report clinical features and outcomes of the first cohort of TAVI performed from Jun 2015 to Jun 2017 in Korea. METHODS: The first cohort of Korean-TAVI (K-TAVI) registry includes 576 consecutive patients with severe symptomatic aortic stenosis who underwent TAVI from 17 Korean hospitals for 2 years. RESULTS: Most of TAVI procedures were performed for septuagenarians and octogenarians (90.8%) through transfemoral approach (98.3%). The rate of device success was 92.5% and permanent pacemaker was implanted in 5.6%. In successive years, incidences of paravalvular leakage (PVL) and major bleeding declined. Society of Thoracic Surgeons (STS) score was 5.2 (3.0 to 9.0) and 34.7% of patients had high surgical risk (STS ≥8). One-year all-cause death occurred in 8.9% and was significantly lower in low to intermediate risk one than in high risk (5.4% vs. 15.5%, p < 0.001). The independent predictors of 1-year mortality were age (hazard ratio [HR], 1.087; 95% confidence interval [CI], 1.036–1.141; p=0.001), moderate or severe PVL (HR, 4.631; 95% CI, 1.624–13.203; p=0.004) and end-stage renal disease (HR, 5.785; 95% CI, 2.717–12.316; p < 0.001). CONCLUSIONS: K-TAVI registry showed favorable 1-year outcomes with decreasing complication rate over time in real-world Korean patients. Two-thirds of patients were low to intermediate surgical risk and showed a significantly lower mortality than the high-risk patients, suggesting the promising future on the expanded indications of TAVI.
Aged, 80 and over ; Aortic Valve Stenosis ; Asian Continental Ancestry Group ; Cohort Studies ; Hemorrhage ; Humans ; Incidence ; Kidney Failure, Chronic ; Korea ; Mortality ; Surgeons ; Transcatheter Aortic Valve Replacement

BACKGROUND AND OBJECTIVES: There has been no nation-wide data on the outcomes of transcatheter aortic valve implantation (TAVI) after commercialization of TAVI in Korea. We report clinical features and outcomes of the first cohort of TAVI performed from Jun 2015 to Jun 2017 in Korea. METHODS: The first cohort of Korean-TAVI (K-TAVI) registry includes 576 consecutive patients with severe symptomatic aortic stenosis who underwent TAVI from 17 Korean hospitals for 2 years. RESULTS: Most of TAVI procedures were performed for septuagenarians and octogenarians (90.8%) through transfemoral approach (98.3%). The rate of device success was 92.5% and permanent pacemaker was implanted in 5.6%. In successive years, incidences of paravalvular leakage (PVL) and major bleeding declined. Society of Thoracic Surgeons (STS) score was 5.2 (3.0 to 9.0) and 34.7% of patients had high surgical risk (STS ≥8). One-year all-cause death occurred in 8.9% and was significantly lower in low to intermediate risk one than in high risk (5.4% vs. 15.5%, p < 0.001). The independent predictors of 1-year mortality were age (hazard ratio [HR], 1.087; 95% confidence interval [CI], 1.036–1.141; p=0.001), moderate or severe PVL (HR, 4.631; 95% CI, 1.624–13.203; p=0.004) and end-stage renal disease (HR, 5.785; 95% CI, 2.717–12.316; p < 0.001). CONCLUSIONS K-TAVI registry showed favorable 1-year outcomes with decreasing complication rate over time in real-world Korean patients. Two-thirds of patients were low to intermediate surgical risk and showed a significantly lower mortality than the high-risk patients, suggesting the promising future on the expanded indications of TAVI.

Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories—mutations, gene rearrangements, and amplifications—and propose expanded guidelines on molecular testing of lung cancers.
Biomarkers ; Gene Rearrangement ; Humans ; Lung Neoplasms* ; Lung* ; Lymphoma ; Pathology, Molecular ; Phosphotransferases ; Precision Medicine ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.
Biopsy ; Chemoradiotherapy* ; Disease-Free Survival ; Follow-Up Studies ; Glioblastoma* ; Humans ; Korea* ; Methylation ; Radiotherapy ; Retrospective Studies* ; Survival Rate

BACKGROUND/AIMS: There are no studies that looked into the bubble eliminating efficacy of polyethylene glycol with ascorbic acid (PEGA), which has been one of the shortcomings of polyethylene glycol (PEG). In this study, we compared newly introduced PEGA regimen by adding either simethicone or 1 L of water. METHODS: A prospective randomized controlled study was carried out at Dongguk Universtiy Gyeongju Hospital from July 2014 to September 2014. A total of 90 patients were randomly assigned to 3 groups; PEGA group (n=30) which served as control, simethicone addition group (n=30) to which simethicone 400 mg was additionally prescribed, and water addition group (n=30) to whom additional 1 L of water was given. Cleansing effectiveness, gas elimination efficacy, side effects, and patient satisfaction were compared between the groups. RESULTS: PEGA group demonstrated the highest cleansing effectiveness, but there was no statistically significant difference among the groups. Simethicone addition group showed significantly lesser amount of bubbles than the other groups (2.57±2.05 vs. 1.10±1.83 vs. 2.60±2.84, p=0.017). The rates of side effects in each group were 20.00% vs. 16.77% vs. 53.33%. Water addition group had significantly more side effects than the PEGA group and the simethicone addition group (p=0.003). The patient satisfaction score of each group was 3.37±0.85 vs. 3.73±0.74 vs. 3.20±0.66 with simethicone addition group showing significantly higher satisfaction than water addition group (p=0.020). CONCLUSIONS: PEGA bowel preparation agent showed satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone resulted in better bubble elimination.
Adult ; Ascorbic Acid/*chemistry ; Cathartics/adverse effects/chemistry/*pharmacology ; Colon/*drug effects ; Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Patient Compliance ; Polyethylene Glycols/adverse effects/*chemistry/pharmacology ; Prospective Studies ; Simethicone/*chemistry ; Water/*chemistry

BACKGROUND: Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. METHODS: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. RESULTS: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. CONCLUSIONS: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.
Adenocarcinoma ; Asian Continental Ancestry Group ; Biopsy ; Carcinoma, Non-Small-Cell Lung* ; Diagnosis ; Epidermal Growth Factor* ; Female ; Humans ; Lung Neoplasms ; Mutation Rate ; Pathology ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor* ; Smoke ; Smoking

PURPOSE: Endobronchial metastasis is defined as documented extrathoracic malignancies metastatic to the endobronchus within a bronchoscopically visible range. Although the clinical and radiologic findings of endobronchial metastasis are similar to primary lung cancer, treatment and prognosis may be different. We hereby investigated the clinical, radiologic and bronchoscopic aspects of endobronchial metastases (EBM) in Korean patients. MATERIALS AND METHODS: A total of 43 patients with EBM who underwent bronchoscopic biopsies from June 1991 to December 2009 at Severance Hospital, Yonsei University College of Medicine in Seoul, Korea, were analyzed retrospectively. We evaluated clinical, radiologic and bronchoscopic characteristics of EBM. RESULTS: The patients consisted of 27 males and 16 females and their ages ranged from 18 to 77 years. The common primary cancers related to EBM were rectal (16.3%), colon (11.6%), breast (9.3%) and uterine (9.3%) cancers. The mean interval from diagnosis of primary cancer to EBM was 36 months, and the mean survival duration from diagnosis of EBM was 16.1 months in 33 deceased patients. CONCLUSION: EBM develop in various types of malignancies at various times with unremarkable manifestations. Therefore, physicians should consider the possibility of EBM, especially if a patient has a history of any malignancy, regardless of respiratory symptoms. Respiratory symptoms related with EBM can be treated by various safe procedures.
Adolescent ; Adult ; Aged ; Breast Neoplasms/pathology ; Bronchial Neoplasms/epidemiology/pathology/*secondary ; Bronchoscopy ; Colonic Neoplasms/pathology ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Rectal Neoplasms/pathology ; Retrospective Studies ; Treatment Outcome ; Uterine Neoplasms/pathology

A 52-year-old man was referred to our clinic for an 11.3 mm nodule in the left lower lobe that was discovered on a chest computed tomography (CT) scan. Eleven small nodules were subsequently found in both lungs. Initially, we performed a transthoracic needle aspiration using CT scan guidance. The pathologic report showed a few clusters of atypical cells that were suspicious for malignancy. The positron emission tomography images revealed multiple lung nodules scattered throughout both lungs. The largest nodule (11.3 mm) in the left lower lobe did not have any discernible fludeoxyglucose uptake. For pathologic confirmation, we consulted a thoracic surgeon to perform the video-assisted thoracoscopic surgery. The final diagnosis was minute pulmonary meningothelial-like nodules (MPMNs). MPMNs are benign in nature, and only a few cases require treatment. However, when clinicians are suspicious of potential malignancy, a pathological correlation is essential, even if the final diagnosis is MPMNs.
Immunohistochemistry ; Lung ; Lung Neoplasms ; Needles ; Neoplasm Metastasis ; Positron-Emission Tomography ; Thoracic Surgery, Video-Assisted ; Thorax

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Humans ; Korea ; Lung ; Lung Neoplasms ; Patient Selection ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Erlotinib Hydrochloride