Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid and inducible nitric oxide synthase/cyclooxygenase-2/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of ALI mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1/ NAD(P)H quinone dehydrogenase 1 in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

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

PURPOSE: Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients. MATERIALS AND METHODS: Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected. RESULTS: Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis. CONCLUSION: Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.
Anthracyclines ; Cardiotoxicity ; Dexrazoxane ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Korea ; Multivariate Analysis ; Neoplasms, Second Primary ; Risk Factors* ; Stem Cell Transplantation

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

BACKGROUND: Childhood immune thrombocytopenic purpura (ITP) is a common acquired bleeding disorder. Even though most children recover, either spontaneously or with therapy, 10-20% of newly diagnosed ITP cases have a chronic course beyond 12 months. This study evaluated whether clinical and laboratory findings can predict the response to intravenous immunoglobulin (IVIG) and progression to persistent or chronic ITP in children. METHODS: During the period between March 2003 and June 2015, we retrospectively analyzed 72 children, newly diagnosed with ITP, who received IVIG treatment. Peripheral blood counts were obtained at diagnosis and at 1, 3, 6, and 12 months after IVIG treatment. RESULTS: After 6 months of IVIG treatment, 14 of 72 patients (19.4%) had persistent ITP, and after 12 months, 7 of 40 patients (17.5%) had chronic ITP. Age at diagnosis, gender, history of viral infection, or vaccination before disease onset were not statistically correlated with platelet recovery at 6 and 12 months. However, a platelet count recovery of ≥100×10(3)/µL at 1 and 3 months was significantly correlated with platelet recovery at 6 (P<0.001 and P<0.001, respectively) and 12 (P=0.007 and P=0.004, respectively) months. CONCLUSION: This study demonstrated that early platelet count recovery, at 1 and 3 months after IVIG treatment, predicts a short disease duration and a favorable outcome in children with newly diagnosed ITP. Further investigation in a larger group of patients is warranted to validate these findings.
Blood Platelets* ; Child* ; Diagnosis ; Hemorrhage ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Platelet Count* ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Vaccination

A 1.1 year old boy was admitted to the Seoul National University Children's Hospital because of incidental findings of hepatosplenomegaly, skin lesion and multiple intra- abdominal lymphadenopathies. Anemia and thrombocytopenia were found based on the initial complete blood count (CBC) measurements. Because of bicytopenia and hepatosplenomegaly, bone marrow examination was performed which revealed hypercellular marrow with increased monocytes and granulopoiesis. The hemoglobin F level was high for his age, and monocyte production was increased. The patient was diagnosed with juvenile myelomonocytic leukemia at the age of 1.2 years. Chemotherapy with cytarabine, etoposide, vincristine, and isotretinoin was initiated. After 6 cycles of chemotherapy, the CBC normalized. He underwent double cord blood transplantation (dCBT), but chimerism studies showed autologous recovery. However, he did not show relapse during the 5 years post-transplant during which he received isotretinoin. He is surviving disease-free 9 years after dCBT.
Anemia ; Blood Cell Count ; Bone Marrow ; Bone Marrow Examination ; Chimerism ; Cytarabine ; Drug Therapy ; Etoposide ; Fetal Blood ; Fetal Hemoglobin ; Humans ; Incidental Findings ; Isotretinoin ; Leukemia, Myelomonocytic, Juvenile ; Male ; Monocytes ; Recurrence ; Seoul ; Skin ; Thrombocytopenia ; Vincristine

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an aggressive malignancy with a poor prognosis. DSRCT is a rare disease, and therefore a standard treatment regimen has not been established. In this study, we reviewed the clinical characteristics and treatment outcomes of pediatric DSRCT patients.METHODS: We retrospectively reviewed the medical records of 5 DSRCT patients (2 boys, 3 girls) that were diagnosed and treated with DSRCT at Seoul National University Children's Hospital from January 1999 to January 2015.RESULTS: The median age at diagnosis was 11 years 5months (range 4 years 10 months-17 years 2 months). The most frequent symptoms were abdominal pain (60%). The primary sites were gastrointestinal tract, bladder, and omentum, and the involved sites were the liver, gastrointestinal tract, bladder and bone. Three patients had multiple metastases at diagnosis. Two patients underwent upfront surgical excision of primary tumor, and the remaining 3 patients received neo-adjuvant chemotherapy after the diagnosis was confirmed by using needle biopsy. Combination chemotherapy was administered to all patients in addition to radiotherapy (median dose 45 Gy, range 17.5-54 Gy). Four patients showed disease progression or relapse, resulting in a 20% overall survival rate. At the time of analysis, one patient is alive. She had localized disease at the time of diagnosis and were treated with upfront surgery, chemotherapy, and high-dose chemotherapy with autologous stem cell transplantation and radiotherapy.CONCLUSION: Patients with DSRCT have a poor prognosis, even after multimodal treatment. Further studies are needed to determine the prognostic factors of DSRCT.
Abdominal Pain ; Biopsy, Needle ; Combined Modality Therapy ; Desmoplastic Small Round Cell Tumor ; Diagnosis ; Disease Progression ; Drug Therapy ; Drug Therapy, Combination ; Gastrointestinal Tract ; Humans ; Korea ; Liver ; Medical Records ; Neoplasm Metastasis ; Omentum ; Pediatrics ; Prognosis ; Radiotherapy ; Rare Diseases ; Recurrence ; Retrospective Studies ; Seoul ; Stem Cell Transplantation ; Survival Rate ; Treatment Outcome ; Urinary Bladder

PURPOSE: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. METHODS: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. RESULTS: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1%) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P=0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P=0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P=0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. CONCLUSION: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.
Alanine Transaminase ; Aspartate Aminotransferases ; Child* ; Drug Monitoring* ; Humans ; Retrospective Studies