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1.  Is a Metallic Microcoil Really a Permanent Embolic Agent for the Management of Distal Guidewire-Induced Coronary Artery Perforation? 
Korean Circulation Journal  2011;41(8):474-478.
Coronary artery perforation (CAP) after percutaneous coronary intervention is a rare, but serious complication. It can cause cardiac tamponade, acute myocardial infarction or death. The treatments of CAP involve prolonged balloon inflation, emergent surgery, coil embolization, and implantation of covered stent. We have successfully performed the emergent microcoil embolization in a patient with uncontrolled Ellis grade 3 guidewire-induced CAP resulting in delayed cardiac tamponade. Contrasting our usual expectation, the 1-year follow-up angiography showed a patent flow at the embolized site.
PMCID: PMC3173669  PMID: 21949533
Embolization, therapeutic; Cardiac tamponade; Angioplasty, balloon, coronary
2.  Successful Treatment by Chemotherapy of Pineal Parenchymal Tumor with Intermediate Differentiation: A Case Report 
A 37-year-old male presented with a mass measuring 2.5 cm in size in the midbrain and obstructive hydrocephalus, which had manifested as a headache and dizziness. Magnetic resonance (MR) imaging of the brain showed intermediate enhancement on T1-weighted MR imaging and a high intensity of enhancement on T2-weighted MR. Neurosurgeons performed an occipital craniotomy with partial removal of the tumor and the postoperative diagnosis was a pineal parenchymal tumor with intermediate differentiation. He had undergone irradiation with 54 Gy of radiation on 27 fractions for removal of the remaining tumor approximately one month after surgery. However, in follow-up imaging performed four months after radiotherapy, a remnant mass in the superoposterior aspect of the midbrain was found to have extended to the hypothalamus and the third ventricle. He was treated with six cycles of procarbazine, lomustine, vincristine chemotherapy. At five months since the completion of chemotherapy, the brain MR imaging showed no evidence of any remaining tumor and he no longer displayed any of his initial symptoms.
PMCID: PMC3804738  PMID: 24155685
Pinealoma; Drug therapy; Radiotherapy; Surgery
3.  The Effects of Preoperative 18F-FDG PET/CT in Breast Cancer Patients in Comparison to the Conventional Imaging Study 
Journal of Breast Cancer  2012;15(4):441-448.
There have been recent studies of the 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) in the staging, detection, and follow-up of the breast cancer occurrence and recurrence. There was controversy concerning the use of 18F-FDG PET/CT for staging primary breast cancer. In this study, we investigated the potential effects of 18F-FDG PET/CT in the initial assessment of patients with primary breast cancer.
From January 2008 to December 2009, 154 consecutive biopsy-proven invasive breast cancer patients were enrolled in this study. Patients underwent conventional imaging studies including mammography, breast ultrasonography (USG), and magnetic resonance imaging for local assessment, and plain chest X-ray, liver USG, and bone scan to rule out distant metastasis. All 154 patients underwent 18F-FDG PET/CT in the initial assessment.
18F-FDG PET/CT did not detect primary breast lesions in 16 patients with a sensitivity of 89.6% and detected only 5 multiple lesions (12.5%) out of 40 cases. Histologically confirmed axillary lymph node (LN) metastases were in 51 patients, and the sensitivity and specificity of 18F-FDG PET/CT to detect metastatic axilla were 37.3% and 95.8%, respectively; whereas the corresponding estimates of USG were 41.2% and 93.7%, respectively. Eleven extra-axillary LN metastases were found in eight patients, and seven lesions were detected by 18F-FDG PET/CT only. The sensitivity and specificity of 18F-FDG PET/CT in detecting distant metastasis were 100% and 96.4%, respectively; whereas the sensitivity and specificity of the conventional imaging were 61.5% and 99.2%, respectively.
18F-FDG PET/CT cannot be recommended as a primary diagnostic procedure in breast cancer, but it has the potential to be used as an additional imaging tool for the detection of axillary metastasis, distant metastasis, and extra-axillary LN metastasis. 18F-FDG PET/CT cannot solely replace the conventional diagnostic procedure in primary breast cancer. The best approach may be the combination of different imaging modalities.
PMCID: PMC3542853  PMID: 23346174
Breast; Carcinoma; Computed tomography; Diagnostic imaging; Positron-emission tomography
4.  Evaluation of Peptide Nucleic Acid Probe-based Real-time PCR for Detection of Mycobacterium tuberculosis Complex and Nontuberculous Mycobacteria in Respiratory Specimens 
Annals of Laboratory Medicine  2012;32(4):257-263.
A peptide nucleic acid (PNA) probe-based real-time PCR (PNAqPCR™ TB/NTM detection kit; PANAGENE, Korea) assay has been recently developed for the simultaneous detection of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) in clinical specimens. The study was aimed at evaluation of the performance of PNA probe-based real-time PCR in respiratory specimens.
To evaluate potential cross-reactivity, the extracted DNA specimens from Mycobacterium species and non-mycobacterial species were tested using PNA probe-based real-time PCR assay. A total of 531 respiratory specimens (482 sputum specimens and 49 bronchoalveolar washing fluid specimens) were collected from 230 patients in July and August, 2011. All specimens were analyzed for the detection of mycobacteria by direct smear examination, mycobacterial culture, and PNA probe-based real-time PCR assay.
In cross-reactivity tests, no false-positive or false-negative results were evident. When the culture method was used as the gold standard test for comparison, PNA probe-based real-time PCR assay for detection of MTBC had a sensitivity and specificity of 96.7% (58/60) and 99.6% (469/471), respectively. Assuming the combination of culture and clinical diagnosis as the standard, the sensitivity and specificity of the new real-time PCR assay for detection of MTBC were 90.6% (58/64) and 99.6% (465/467), respectively. The new real-time PCR for the detection of NTM had a sensitivity and specificity of 69.0% (29/42) and 100% (489/489), respectively.
The new real-time PCR assay may be useful for the detection of MTBC in respiratory specimens and for discrimination of NTM from MTBC.
PMCID: PMC3384806  PMID: 22779066
Peptide nucleic acids; PCR; Mycobacterium tuberculosis; Mycobacterium
5.  Bevacizumab as a second- or later-line of treatment for metastatic colorectal cancer 
AIM: To determine the efficacy of bevacizumab in patients with metastatic colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.
METHODS: Between March 2002 and June 2010, 40 patients in South Korea with MCRC who were treated with bevacizumab plus chemotherapy as a second or later-line treatment were analyzed retrospectively for their overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.
RESULTS: All of the patients had progressed under prior chemotherapy without bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%) exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line, third-line and fourth- or later-line treatments, respectively. The median PFSs were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later-line treatments, respectively.
CONCLUSION: In patients with MCRC, bevacizumab combined chemotherapy may be beneficial during second- or later-line treatment.
PMCID: PMC3296985  PMID: 22416186
Colorectal cancer; Metastasis; Bevacizumab; Efficacy; Second- or later-line
6.  Evaluation of a New Immunochromatographic Assay Kit for the Rapid Detection of Norovirus in Fecal Specimens 
Annals of Laboratory Medicine  2011;32(1):79-81.
Rapid and accurate detection of norovirus is essential for the prevention and control of norovirus outbreaks. This study compared the effectiveness of a new immunochromatographic assay kit (SD BIOLINE Norovirus; Standard Diagnostics, Korea) and real-time reverse transcription-PCR (RT-PCR) for detecting norovirus in fecal specimens. Compared with real-time RT-PCR, the new assay had sensitivity, specificity, positive predictive value, and negative predictive value of 76.5% (52/68), 99.7% (342/343), 98.1% (52/53), and 95.5% (342/358), respectively. The sensitivity of the assay was 81.8% (18/22) for GII.3 and 75.7% (28/37) for GII.4. None of the 38 enteric virus-positive specimens (3 for astrovirus, 5 for enteric adenovirus, and 30 for rotavirus) tested positive in the cross-reactivity test performed by using this assay. The new immunochromatographic assay may be a useful screening tool for the rapid detection of norovirus in sporadic and outbreak cases; however, negative results may require confirmatory assays of greater sensitivity.
PMCID: PMC3255496  PMID: 22259783
Immunochromatographic assay; Norovirus; Sensitivity; Specificity
7.  Left Transradial Coronary Angiography in a Patient With Dextrocardia 
Korean Circulation Journal  2010;40(11):601-603.
Although dextrocardia occurs rarely, the incidence of coronary artery disease is similar to the general population. Because of unfamiliarity with performing catheterization, transradial coronary angiography has seldom been performed in a patient with dextrocardia. We successfully performed left transradial coronary angiography in a patient with a right side heart using counter-directional torquing of the catheters and mirror-image angiographic angles.
PMCID: PMC3008833  PMID: 21217939
Dextrocardia; Coronary angiography
8.  Tracheal calcification 
PMCID: PMC2474880  PMID: 18663210
9.  Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma 
Oncology Letters  2015;9(4):1699-1706.
Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia-inducible factor 1α (HIF-1α) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF-1α, carbonic anhydrase 9 (CA9), glucose transporter-1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression-free survival (PFS) in cases of STS, were investigated. Overexpression of HIF-1α, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF-1α overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF-1α overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF-1α and CA9 is associated with poor prognosis, and that HIF-1α overexpression is an independent unfavorable prognostic factor in STS.
PMCID: PMC4356356  PMID: 25789026
soft tissue sarcoma; carbonic anhydrase 9; hypoxia; hypoxia-inducible factor 1α; glucose transporter-1; vascular endothelial growth factor
10.  Complete Sequence Analysis and Antiviral Screening of Medicinal Plants for Human Coxsackievirus A16 Isolated in Korea 
Coxsackievirus A group 16 strain (CVA16) is one of the predominant causative agents of hand, foot, and mouth disease (HFMD).
Using a specimen from a male patient with HFMD, we isolated and performed sequencing of the Korean CVA16 strain and compared it with a G10 reference strain. Also, we were investigated the effects of medicinal plant extract on the cytopathic effects (CPE) by CPE reduction assay against Korean CVA16.
Phylogenetic analysis showed that the Korean CVA16 isolate belonged to cluster B-1 and was closely related to the strain PM-15765-00 isolated in Malaysia in 2000. The Korean CVA16 isolate showed 73.2% nucleotide identity to the G10 prototype strain and 98.7% nucleotide identity to PM-15765-00. Next, we assessed whether the Korean CVA16 isolate could be used for in vitro screening of antiviral agents to treat HFMD infection. Vero cells infected with the Korean CVA16 isolate showed a cytopathic effect 2 days after the infection, and the treatment of cells with Cornus officinalis, Acer triflorum, Pulsatilla koreana, and Clematis heracleifolia var. davidiana Hemsl extracts exhibited strong antiviral activity against CVA16.
Collectively, our work provides potential candidates for the development of vaccine and novel drugs to treat the CVA16 strain isolated from a Korean patient.
PMCID: PMC4346589  PMID: 25737832
coxsackievirus A16; antiviral drug; HFMD; medicinal plant
11.  Analysis of the Prognostic Factors for Distant Metastasis after Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Head and Neck Cancer 
The aim of this study is to identify the prognostic factors of distant metastasis (DM) after induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) for locoregionally advanced head and neck cancer (HNC).
Materials and Methods
A total of 321 patients with HNC who underwent IC followed by CRT treated between January 2005 and December 2010 were analyzed retrospectively. IC consisted of three courses of docetaxel (70 mg/m2) and cisplatin (75 mg/m2) every three weeks, followed by radiotherapy of 66-70 Gy/2 Gy per fraction/5 fractions per week concurrent with weekly cisplatin (40 mg/m2). Tumor/nodal stage, primary site, tumor differentiation, lower neck node involvement (level IV, VB, and supraclavicular regions), number of concurrent chemotherapy cycles, overall duration of radiotherapy, and response to IC were assessed as potential prognostic factors influencing DM and survival outcome.
The five-year loco-regional recurrence and DM rates were 23.6% and 18.2%. N stage, overall duration of radiotherapy, lower neck node involvement, and response to IC were significant factors for DM. With a median follow-up period of 52 months (range, 4 to 83 months), the 5-year progression-free, DM-free, and overall survival rates were 41.2%, 50.7%, and 55.1%, respectively. Lower neck node involvement (p=0.008) and poor response to IC (p < 0.001) showed an association with significantly inferior DM-free survival.
Even with the addition of IC, the DM rate and survival outcome were poor when metastatic lower neck lymph nodes were present or when patients failed to respond after receiving IC.
PMCID: PMC4296855  PMID: 25327492
Head and neck neoplasms; Chemoradiotherapy; Induction chemotherapy; Neoplasm metastasis; Prognosis
12.  Treatment of Dexamethasone-Induced Hiccup in Chemotherapy Patients by Methylprednisolone Rotation 
The Oncologist  2013;18(11):1229-1234.
Dexamethasone-induced hiccup (DIH) is an underrecognized symptom in patients with cancer, and little information is available about its treatment. The aims of this study were to investigate the feasibility of methylprednisolone rotation as treatment and to confirm the male predominance among those with cancer who experienced DIH during chemotherapy. DIH during chemotherapy could be controlled without losing antiemetic potential by replacing dexamethasone with methylprednisolone.
Dexamethasone-induced hiccup (DIH) is an underrecognized symptom in patients with cancer, and little information is available about its treatment. The aims of this study were to investigate the feasibility of methylprednisolone rotation as treatment and to confirm the male predominance among those with cancer who experienced DIH during chemotherapy.
Persons with cancer who experienced hiccups during chemotherapy treatment and who were receiving treatment with dexamethasone were presumed to have DIH. The following algorithmic practice was implemented for antiemetic corticosteroid use: rotation from dexamethasone to methylprednisolone in the next cycle and dexamethasone re-administration in the second cycle of chemotherapy after recognition of hiccups to confirm DIH. All other antiemetics except corticosteroid remained unchanged. Patients (n = 40) were recruited from eight cancer centers in Korea from September 2012 to April 2013. Data were collected retrospectively.
Hiccup intensity (numeric rating scale [NRS]: 5.38 vs. 0.53) and duration (68.44 minutes vs. 1.79 minutes) were significantly decreased after rotation to methylprednisolone, while intensity of emesis was not increased (NRS: 2.63 vs. 2.08). Median dose of dexamethasone and methylprednisolone were 10 mg and 50 mg, respectively. Thirty-four (85%) of 40 patients showed complete resolution of hiccups after methylprednisolone rotation in the next cycle. Of these 34 patients, 25 (73.5%) had recurrence of hiccups after dexamethasone re-administration. Compared with baseline values, hiccup intensity (NRS: 5.24 vs. 2.44) and duration (66.43 minutes vs. 22.00 minutes) were significantly attenuated after dexamethasone re-administration. Of the 40 eligible patients, 38 (95%) were male.
DIH during chemotherapy could be controlled without losing antiemetic potential by replacing dexamethasone with methylprednisolone. We also identified a male predominance of DIH. Further prospective studies are warranted.
PMCID: PMC3825309  PMID: 24107973
Dexamethasone; Hiccup; Methylprednisolone; Corticosteroids
13.  Knockdown of Bcl-xL Enhances Growth-Inhibiting and Apoptosis-Inducing Effects of Resveratrol and Clofarabine in Malignant Mesothelioma H-2452 Cells 
Journal of Korean Medical Science  2014;29(11):1464-1472.
Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.
Graphical Abstract
PMCID: PMC4234912  PMID: 25408576
Mesothelioma, Malignant; Mcl-1; Bcl-xL; Resveratol; Clofarabine; Apoptosis
14.  Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study 
To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain.
Materials and Methods
One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator’s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated.
A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea.
HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.
PMCID: PMC4206066  PMID: 25043822
Cancer pain; Sleep disturbance; Hydromorphone-OROS (HM-OROS)
15.  Changes in Osteoblastic Activity in Patient Who Received Bortezomib as Second Line Treatment for Plasma Cell Myeloma: A Prospective Multicenter Study 
BioMed Research International  2014;2014:245247.
We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.
PMCID: PMC4094867  PMID: 25050331
16.  The Role of Hand-Assisted Laparoscopic Surgery in a Right Hemicolectomy for Right-Sided Colon Cancer 
Annals of Coloproctology  2014;30(1):11-17.
The purpose of this study is to evaluate the perioperative and long-term oncologic outcomes of hand-assisted laparoscopic surgery (HALS) and standard laparoscopic surgery (SLS) and assess the role of HALS in the management of right-sided colon cancer.
The study group included 53 patients who underwent HALS and 45 patients who underwent SLS for right-sided colon cancer between April 2002 and December 2008.
The patients in each group were similar in age, American Society of Anesthesiologist (ASA) score, body mass index, and history of previous abdominal surgeries. Eight patients in the HALS group and no patient in the SLS group exhibited signs of tumor invasion into adjacent structures. No differences were noted in the time to return of normal bowel function, time to toleration of diet, lengths of hospital stay and narcotic usage, and rate of postoperative complications. The median incision length was longer in the HALS group (HALS: 7.0 cm vs. SLS: 4.8 cm, P < 0.001). The HALS group had a significantly higher pathologic TNM stage and significantly larger tumor size (HALS: 6.0 cm vs. SLS: 3.3 cm, P < 0.001). The 5-year overall, disease-free, and cancer-specific survival rates of the HALS and the SLS groups were 87.3%, 75.2%, and 93.9% and 86.4%, 78.0%, and 90.7%, respectively (P = 0.826, P = 0.574, and P = 0.826).
Although patients in the HALS group had more advanced disease and underwent more complex procedures than those in the SLS group, the short-term benefits and the oncologic outcomes between the two groups were comparable. HALS can, therefore, be considered an alternative to SLS for bulky and fixed right-sided colon cancer.
PMCID: PMC3953162  PMID: 24639965
Colonic neoplasms; Laparoscopy; Hand-assisted laparoscopy
17.  Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review 
There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.
PMCID: PMC3895737  PMID: 24400686
Breast; Neoplasm; Phyllodes tumor; Ductal carcinoma; Inflammatory breast carcinoma
18.  Success Rate and Risk Factors for Failure of Empirical Antifungal Therapy with Itraconazole in Patients with Hematological Malignancies: A Multicenter, Prospective, Open-Label, Observational Study in Korea 
We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
PMCID: PMC3890478  PMID: 24431907
Hematological Malignancy; Itraconazole; Empirical Antifungal Therapy; Galactomannan Test
19.  Development of a Specific and Rapid Diagnostic Method for Detecting Influenza A (H1N1) pdm09 Virus Infection Using Immunochromatographic Assay 
The aim of this study was to develop an immunochromatographic assay (ICA) for the detection of influenza A (H1N1) pdm09 virus infection.
Materials and methods
Several monoclonal antibodies against influenza A (H1N1) pdm09 virus were generated and an ICA (pdm09-ICA) was developed for the rapid and specific detection of influenza A (H1N1) pdm09 virus infection. The specificity and sensitivity of the developed assay were compared with that of hemagglutination assay and real-time reverse-transcription polymerase chain reaction (rRT-PCR).
The detection limit was estimated to be 1/2 (8) hemagglutinating unit; the sensitivity and specificity rates of pdm09-ICA were 75.86% (110/145) and 100% (43/43), respectively, compared with rRT-PCR. The cross-reactivity for 20 influenza viruses, including seasonal H1N1 viruses, was found to be negative except for the H1N1 virus (A/Swine/Korea/GC0503/2005).
These results indicate that the proposed method can be easily used for rapid and specific detection of the pdm09 infection. The assay developed in this study would be a useful tool for distinguishing the pdm09 infection from seasonal influenza A and B infections.
PMCID: PMC3922102  PMID: 24524023
immunochromatographic assay; immunochromatography test; influenza; pdm09
20.  Predicting Survival in Patients with Advanced Non-squamous Non-small Cell Lung Cancer: Validating the Extent of Metastasis 
A number of factors related to overall survival (OS) have been addressed in advanced non-small cell lung cancer (NSCLC). This study was conducted to determine the impact of whole-body metastatic regions on survival outcome in advanced non-squamous NSCLC.
Materials and Methods
Between March 2005 and February 2011, 112 eligible patients with newly confirmed stage IV non-squamous NSCLC, available for epidermal growth factor receptor (EGFR) mutation status 18-21 analysis, and accessible for the determination of pretreatment whole-body metastatic regions were enrolled in this retrospective study. The total number of synchronous metastatic regions was scored according to the following disease sites: abdomen/pelvis, lung to lung/pulmonary lymphangitic spread, bone, pleura/pleural effusion/pericardial effusion, neck/axillary lymph nodes, other soft tissue, brain.
The median age of the cohort was 65 years (range, 31 to 88 years). The median whole-body metastatic score was 2 (range, 1 to 6), and bone and lung to lung were the most common metastatic sites. EGFR mutations were observed in 40 (35.7%) patients with a deletion in exon 19 and Leu858Arg mutation in exon 21 being detected in 16 (40.0%) and 19 (47.5%) patients, respectively. Multivariate analysis for OS revealed that treatment factors (p=0.005), performance status (p=0.006), whole-body metastatic score (p<0.001), and EGFR mutation status (p=0.095) were significantly or marginally associated with OS.
The results of the present study demonstrated that whole-body metastatic extent strongly affects survival outcome, even after adjustment for other significant variables in advanced non-squamous NSCLC. The clinical validity of more curative multimodal approaches in cohorts with limited metastases remains to be explored.
PMCID: PMC3710968  PMID: 23864842
Epidermal growth factor receptor; Mutation; Adenocarcinoma of lung; Neoplasm metastasis; Non-small cell lung carcinoma; Prognosis
21.  Evaluation of Short-Term Use of N-Acetylcysteine as a Strategy for Prevention of Anthracycline-Induced Cardiomyopathy: EPOCH Trial - A Prospective Randomized Study 
Korean Circulation Journal  2013;43(3):174-181.
Background and Objectives
We investigate to determine whether N-acetylcysteine (NAC) can prevent anthracycline-induced cardiotoxicity.
Subjects and Methods
A total of 103 patients were enrolled in this prospective randomized open label controlled trial. They are patients first diagnosed with breast cancer or lymphoma, who require chemotherapy, including anthracycline like adriamycine or epirubicine. Patients were randomized to the NAC group {n=50; 1200 mg orally every 8 hours starting before and ending after the intravenous infusion of anthracycline in all chemotherapy cycles (3-6)} or the control group (n=53). Primary outcome was the decrease in left ventricular ejection fraction (LVEF) absolutely ≥10% from the baseline and concomitantly <50% at 6-month. Composite of all-cause death, heart failure and readmission were compared.
The primary outcome was not significantly different in the NAC and control groups {3/47 (6.4%) vs. 1/52 (1.9%), p=0.343}. The mean LVEF significantly decreased in both the NAC (from 64.5 to 60.8%, p=0.001) and control groups (from 64.1 to 61.3%, p<0.001) after the completion of whole chemotherapy. The mean LVEF change did not differ between the two groups (-3.64% in NAC vs. -2.78% in control group, p=0.502). Left ventricular (LV) end systolic dimension increased with higher trend in NAC by 3.08±4.56 mm as compared with 1.47±1.83 mm in the control group (p=0.064). LV end diastolic dimension did not change in each group and change does not differ in both. Peak E, A and E/A ratio change and cardiac enzymes were comparable in two groups. Cumulative 12-month event rate was 6% and 3.8% in the NAC group and the control group, respectively, with no difference (p=0.672).
We cannot prove that NAC prevents anthracycline-induced cardiomyopathy.
PMCID: PMC3629243  PMID: 23613694
Acetylcysteine; Anthracyclines; Cardiomyopathies
22.  S100A2 Level Changes Are Related to Human Periodontitis 
Molecules and Cells  2011;32(5):445-450.
Periodontitis is an inflammatory disease, which, when severe, can result in tooth loss, that affects the quality of life. S100A2 was previously identified as a component of gingival crevicular fluid (GCF) via proteome analysis, but it has not been investigated whether S100A2 plays a role in periodontitis. In this study, we analyzed mRNA expression of S100A2 in gingival tissues from normal and classified periodontal disease patients and compared it to that of S100A8 and S100A9. Quantitative real time-PCR revealed that the mRNA expression levels of S100A2, S100A8, and S100A9 were significantly upregulated in gingival tissues with gingivitis, moderate periodontitis, and severe periodontitis compared to normal tissues. In addition, S100A2 proteins in GCF and the conditioned media of lipopolysaccharide (LPS)-treated Jurkat cells were confirmed by ELISA. S100A2 protein levels were significantly higher in GCF in gingivitis and moderate periodontitis groups than in normal groups. S100A2 mRNA expression and protein secretion were also increased by LPS stimulation. Based on the up-regulation of S100A2 in LPS-stimulated immune cells, gingival tissues and GCF from periodontal disease groups, we conclude that S100A2 is a functional component in the immune response during periodontitis and may serve as a potential biomarker for periodontitis.
PMCID: PMC3887693  PMID: 21922197
gingival crevicular fluid; gingival tissue; lipopolysaccharide; periodontitis; s100a2
23.  Effect of Activated Charcoal Fibers on the Survival of the House Dust Mite, Dermatophagoides pteronyssinus: A Pilot Study 
ISRN Allergy  2012;2012:868170.
House dust mites produce potent allergens that exacerbate asthma in sensitized patients, whom are recommended to practice allergen avoidance within their home environment. We tested the effect of activated charcoal impregnated fibers on house dust mite survival. One hundred live adult house dust mites (Dermatophagoides pteronyssinus) were added to eight culture dishes preequilibrated at room temperature (n = 4) and 70% humidity (n = 4) containing house dust mite food and active charcoal fibers. At 10 minute intervals, live and dead house dust mites were counted. All house dust mites instantly attached to the activated charcoal fibers and started to shrink almost immediately. There were no live house dust mites present as early as 40 minutes in some dishes while after 190 minutes all house dust mites were dead. In conclusion, activated charcoal fibers, if incorporated into bedding items, have the potential to control house dust mites in the indoor environment.
PMCID: PMC3671713  PMID: 23762605
24.  Enterovirus infection in Korean children and anti-enteroviral potential candidate agents 
Korean Journal of Pediatrics  2012;55(10):359-366.
Although most enterovirus infections are not serious enough to be life threatening, several enteroviruses such as enterovirus 71 are responsible for severe, potentially life-threatening disease. The epidemic patterns of enteroviruses occur regularly during the year, but they may change due to environmental shifts induced by climate change due to global warming. Therefore, enterovirus epidemiological studies should be performed continuously as a basis for anti-viral studies. A great number of synthesized antiviral compounds that work against enteroviruses have been developed but only a few have demonstrated effectiveness in vivo. No proven effective antiviral agents are available for enterovirus disease therapy. The development of a new antiviral drug is a difficult task due to poor selective toxicity and cost. To overcome these limitations, one approach is to accelerate the availability of other existing antiviral drugs approved for antiviral effect against enteroviruses, and the other way is to screen traditional medicinal plants.
PMCID: PMC3488610  PMID: 23133481
Enterovirus; Antiviral agents; Medicinal plants
25.  Polyarteritis Nodosa Complicated by Chronic Total Occlusion Accompanying Aneurysms on All Coronary Arteries 
Korean Circulation Journal  2012;42(8):568-570.
Polyarteritis nodosa (PAN) is characterized by inflammatory necrosis of medium sized arteries. PAN can also be associated with stenosis or aneurysm of the coronary artery. However, the involvement of PAN at a coronary artery is usually asymptomatic, which makes it difficult to diagnose. In addition, all of the three main coronary arteries involved with chronic total occlusion (CTO) is a rare finding in patients with PAN. We report a patient that presented with PAN complicated by CTO and aneurysms of three main coronary arteries, without typical symptoms of angina.
PMCID: PMC3438269  PMID: 22977455
Polyarteritis nodosa; Coronary aneurysm; Coronary occlusion

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