Young Hyeh Ko

Sungkyunkwan University, Sŏul, Seoul, South Korea

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Publications (85)256.7 Total impact

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    ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis.
    Cancer research and treatment : official journal of Korean Cancer Association. 07/2014; 46(3):307-311.
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    ABSTRACT: A 60-year-old woman suffered from recurrent femur neck fracture. Laboratory data showed serum hypophosphatemia, elevated alkaline phosphatase, normal serum calcium levels, and normal parathyroid hormone levels. Radiological examinations revealed a tumor in the right maxillary alveolar bone. The nasal cavity mass was removed, and the histological features were those of glomangiopericytoma. After removal of the tumor, some of the laboratory data normalized. Based on the clinical features, histopathological diagnosis and postoperative course of events, a diagnosis of glomangiopericytoma causing oncogenic osteomalacia was confirmed. We report a case of oncogenic osteomalacia caused by sinonasal glomangiopericytoma.
    Clinical and Experimental Otorhinolaryngology 06/2014; 7(2):145-8. · 0.88 Impact Factor
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    ABSTRACT: The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further examination of the RHOA mutation encoding p.Gly17Val in 239 lymphoma samples showed that the mutation was specific to T cell lymphoma and was absent from B cell lymphoma. We demonstrate that the RHOA mutation encoding p.Gly17Val, which was found in 53.3% (24 of 45) of the AITL cases examined, is oncogenic in nature using multiple molecular assays. Molecular modeling and docking simulations provided a structural basis for the loss of GTPase activity in the RHOA Gly17Val mutant. Our experimental data and modeling results suggest that the RHOA mutation encoding p.Gly17Val is a driver mutation in AITL. On the basis of these data and through integrated pathway analysis, we build a comprehensive signaling network for AITL oncogenesis.
    Nature Genetics 03/2014; · 35.21 Impact Factor
  • Sanghui Park, Young Hyeh Ko
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    ABSTRACT: Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T- and NK-cell neoplasms, the incidence of which is higher in Asian countries than in Western countries. Although its etiology is mainly unknown, several risk factors (such as genetic factors, abnormal immunity, environmental factors, and infectious causes) have been proposed. PTCL are classified based on a combination of several parameters, including morphology, site of presentation, viral status, immunophenotype, and specific genetic alterations. Their classification is ongoing, with the emergence of new entities and refinement of existing entities because of the development of diagnostic markers and new genetic alterations. This review presents epidemiologic data for PTCL in Asia, together with recent progress in the pathology of PTCL compared with the WHO 2008 classification.
    International journal of hematology 01/2014; · 1.17 Impact Factor
  • Hematological Oncology 01/2014; · 2.04 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment.
    Genomics 01/2014; · 3.01 Impact Factor
  • Leukemia & lymphoma 12/2013; · 2.40 Impact Factor
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    ABSTRACT: Background: T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is a rare morphological variant of diffuse large B cell lymphoma (DLBCL), accounting for 1-3% of all DLBCLs. However, its impact on treatment outcome and prognosis is still not clearly defined. Methods: We compared the clinical outcomes between THRLBCL and DLBCL, not otherwise specified (NOS), in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Results: Data from 11 patients with THRLBCL were matched to 33 patients with DLBCL-NOS. Patients were matched by five established prognostic factors of the International Prognostic Index, including age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase level and the number of extranodal involvement. There was no significant difference in the complete response rate to R-CHOP between THRLBCL (91%, 10/11) and DLBCL-NOS (97%, 32/33; p = 0.442). The 3-year event-free survival rate was 81% for both THRLBCL and DLBCL-NOS (p = 0.813). The 3-year overall survival rates were 75 and 81%, respectively (p = 0.719). Conclusions: The treatment outcomes of THRLBCL are similar to those of DLBCL-NOS. The addition of rituximab to CHOP seems to be helpful for the management of THRLBCL, as it is for DLBCL-NOS. © 2013 S. Karger AG, Basel.
    Acta Haematologica 10/2013; 131(3):156-161. · 0.89 Impact Factor
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    ABSTRACT: Mutations in 2 upstream components of the nuclear factor κB (NF-κB) pathway, CD79B and MYD88, are important information for new target therapy in malignant lymphoma. We examined the prevalence and clinicopathologic characteristics of CD79B and MYD88 mutation in a cohort of Asian diffuse large B cell lymphoma (DLBCL) patients. CD79B and MYD88 mutations were analyzed by Sanger sequencing in 187 DLBCL tissue samples. CD79B immunoreceptor tyrosine-based activation motif spanning exon 5 and 6 and MYD88 TIR domain spanning exons 3, 4 and 5 were amplified and sequenced. The cell-of-origin was determined based on immunohistochemical stains for CD10, BCL-6 and MUM-1 by Hans' algorithm. CD79B was mutated in 16 cases (8.5%), mostly involving the first tyrosine (Y196) of immunoreceptor tyrosine-based activation motif. For MYD88, L265P mutation was found in 31 cases (out of 161, 19.3%). In 11 of these, a CD79B mutation coexisted, which constituted 69% of CD79B mutants and 36% of MYD88 L265P cases. Clinicopathologic comparison between the mutant and the wild-type group showed that the mean age was older for both CD79B (66 versus 58 years) and MYD88 L265P mutant groups (64 versus 58 years). Survival analyses showed that neither CD79B mutation nor MYD88 L265P was a significant prognostic indicator. In conclusion, CD79B and MYD88 mutations are associated with an older age at onset in DLBCL with a significant overlap, which did not affect the outcome of the disease.
    Human pathology 10/2013; · 3.03 Impact Factor
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    ABSTRACT: To evaluate the clinical outcomes of radiation therapy (RT) for early-stage gastric mucosa-associated lymphoid tissue lymphoma (MALToma). The records of 64 patients treated between 1998 and 2011 were analyzed retrospectively. For Helicobacter pylori (H. pylori)-positive patients (n = 31), chemotherapy or H. pylori eradication therapy was the initial treatment. In patients with failure after H. pylori eradication, RT was performed. For H. pylori-negative patients (n = 33), chemotherapy or RT was the first-line treatment. The median RT dose was 36 Gy. The target volume included the entire stomach and the perigastric lymph node area. All of the patients completed RT without interruption and showed complete remission on endoscopic biopsy after treatment. Over a median follow-up period of 39 mo, the 5-year local control rate was 89%. Salvage therapy was successful in all relapsed patients. Secondary malignancies developed in three patients. The 5-year overall survival rate was 94%. No patient presented symptoms of moderate-to-severe treatment-related toxicities during or after RT. Radiotherapy results in favorable clinical outcomes in patients with early-stage gastric MALToma who experience failure of H. pylori eradication therapy and those who are H. pylori negative.
    World Journal of Gastroenterology 09/2013; 19(36):6062-6068. · 2.55 Impact Factor
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    ABSTRACT: Background: Clinical features and treatment outcomes of intravascular large B-cell lymphoma (IVLBCL) have rarely been reviewed due to its rarity and pathologic obscurity. Methods: We analyzed 20 patients who were pathologically diagnosed with IVLBCL at the Samsung Medical Center. Results: Initial manifestations were nonspecific, such as fever with cytopenia, elevated serum lactate dehydrogenase and hypoalbuminemia. Hemophagocytosis was frequent and bone marrow was the most common site of pathologic diagnosis in our series. Hepatosplenomegaly, pleural effusion and ground-glass opacity in the lungs were also commonly found, and positron emission tomography imaging showed increased (18)F-fluorodeoxyglucose uptake in the involved organs. All patients received CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or rituximab-CHOP. The median overall survival (OS) was 38.9 months (95% confidence interval 6.7-71.1). Rituximab-containing chemotherapy compared to chemotherapy alone resulted in higher 3-year OS (71.4 and 25.0%; p = 0.027). Patients with hemophagocytosis had a poorer 3-year OS compared to patients without hemophagocytosis (29.6 and 75%; p = 0.046). Prognostic factor analysis showed the association of pleural effusion with worse OS (p = 0.002). Conclusions: Treatment with rituximab-containing chemotherapy can improve the treatment outcome of IVLBCL. Pleural effusion may be a poor prognostic factor in patients with IVLBCL. © 2013 S. Karger AG, Basel.
    Acta Haematologica 09/2013; 131(1):18-27. · 0.89 Impact Factor
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    ABSTRACT: We performed the whole genome cDNA-mediated annealing, selection and ligation assay with 164 formalin-fixed paraffin-embedded (FFPE) tumor samples to develop robust prognostic gene expression profiles in patients with diffuse large B cell lymphoma. The prognostic gene expression profiles were developed and validated by a gradient lasso and leave-one-out cross-validation process. We identified a set of genes whose expression provided prognostic indicators from whole data set (PRKCDBP, CASP10, FAM3C, KCNK12, MAN1A2, PRND, RAB1A, TMEM39B, SLC6A6, MMP12, FEM1B, C3orh37, RBP1, HK1, LOC400464, KIAA0746, and SLC25A23). This gene expression profile-based risk model could classify patients into two cross-validated risk groups with a significant difference in 5-year progression-free survival rates (71.1 vs. 45.5 %) and with a hazard ratio for recurrence of 2.45 (95 % CI, 1.44-4.16, P = 0.001). This model provided prognostic information independent of the International Prognostic Index (IPI), and discriminated high-risk group from patients belong to high/high-intermediate risk of IPI and activated B cell-like type. Thus, gene expression profiling from FFPE could provide additional prognostic information for diffuse large B cell lymphoma and our data underscore the need for development of risk-adapted treatment strategies based on gene expression profiles.
    Annals of Hematology 08/2013; · 2.87 Impact Factor
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    ABSTRACT: Background We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). Methods Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m2 cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2) (maximum 2 mg) vincristine on day 1, and 100 mg/day prednisone on days 1 to 5) every 21 days were planned. Results Fifteen patients newly diagnosed with stage III/IV PTCL were enrolled. One of 6 patients at dose level 2 (5 mg everolimus) had grade 3 hepatotoxicity and 3 of 6 patients at level 3 (7.5 mg everolimus) had grade 4 hematologic toxicities (two grade 4 thrombocytopenia and one grade 4 neutropenia with fever lasting more than 3 days). The recommended dose of everolimus for combination was 5 mg. There were no differences in steady state trough concentrations of everolimus between cycles 1 and 2 for all three dose levels. All evaluable patients achieved response (8 complete and 6 partial). Conclusions Everolimus (5 mg) can be safely combined with CHOP leading to a feasible and effective regimen for PTCL. The subsequent phase II is now in progress.
    Investigational New Drugs 08/2013; · 3.50 Impact Factor
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    ABSTRACT: Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among the broad category of non-Hodgkin lymphomas. Owing to the lack of specific genetic alterations in the vast majority, most currently defined entities show overlapping morphological and immunophenotypic features, and therefore pose a challenge to the diagnostic pathologist. In the light of recent immunophenotypic, cytogenetic and molecular genetics advances in the field of T-cell and T/NK-cell lymphomas, the focus of the lymphoma workshop of the European Association for Haematopathology/Society for Hematopathology meeting in Lisbon, Portugal, in October 2012 was to refine existing diagnostic criteria and clarify the borders between overlapping entities. The panel reviewed over 200 submitted cases, which were grouped into five categories: (i) angioimmunoblastic T-cell lymphoma and T-follicular-helper-cell-associated lymphomas; (ii) CD30-positive T-cell lymphomas/lymphoproliferative diseases; (iii) extranodal T-cell and NK-cell neoplasms; (iv) EBV-associated T-cell/NK-cell lymphomas/lymphoproliferative diseases; and (v) peripheral T-cell lymphoma, not otherwise specified, post-transplant lymphoproliferative disorders, and mimics. This report summarizes the discussions and conclusions of the workshop, which question current diagnostic criteria and provide recommendations for refining existing classifications.
    Histopathology 08/2013; · 2.86 Impact Factor
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    ABSTRACT: The New York protocol, primarily developed to treat children with high-risk acute lymphoblastic leukemia (ALL), is characterized by early intensive chemotherapy followed by less intensive pulse chemotherapy during maintenance. This study was performed to evaluate the efficacy of this protocol in children with non-Hodgkin lymphoma (NHL), irrespective of histopathologic subtype. From January 1996 to December 2011, 146 newly diagnosed children and adolescents with NHL were treated with the modified New York protocol. Treatment duration was determined according to the stage. The 5-year failure-free survival (FFS), event-free survival (EFS), and overall survival (OS) rates were 86.7 ± 2.9%, 79.1 ± 3.5%, and 84.7 ± 3.1%, respectively. The 5-year FFS for patients with mature B-cell lymphoma, T-cell and NK-cell lymphoma (T/NK-cell lymphoma), and lymphoblastic lymphoma were 95.4 ± 2.6%, 76.1 ± 7.0%, and 82.1 ± 6.6%, respectively. In multivariate analysis, T/NK-cell lymphoma and non-complete response (non-CR) at the end of induction chemotherapy were associated with a significant increase in treatment failure rate (relative risk [RR], 4.5, P = 0.03, and RR, 5.0, P = 0.002). The protocol appears to be efficacious in the treatment of children and adolescents with NHL, irrespective of histopathologic subtype. Achievement of CR after intensive induction chemotherapy was an important prognostic factor. Early response to treatment may be used to stratify risk groups and modify therapy in children with NHL. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 07/2013; · 2.35 Impact Factor
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    ABSTRACT: The occurrence of Ewing sarcoma as a secondary malignancy is an extremely rare event in long-term cancer survivors. In addition, the occurrence of Ewing sarcoma in the adrenal gland is highly unusual. In this case report, we treated a 20-year-old male patient with cyclophosphamide, doxorubicin, vincristine, dexamethasone, and methotrexate and cytarabine chemotherapy following a diagnosis of Stage IV Burkitt lymphoma. Following complete remission, he had been maintained for 2 years without evidence of disease. However, a regular follow-up computed tomography scan found a left adrenal gland mass and a biopsy revealed positive membrane-localized mic-2 expression (CD99) and the presence of the translocation of the EWSR1 gene. To our knowledge, this is the first case report of Ewing sarcoma occurring in the adrenal gland of a patient who was treated with cyclophosphamide, doxorubicin, vincristine, dexamethasone/methotrexate and cytarabine chemotherapy for Burkitt lymphoma.
    Japanese Journal of Clinical Oncology 04/2013; · 1.90 Impact Factor
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    ABSTRACT: Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality. Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed. STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis. EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.
    The Korean Journal of Pathology 04/2013; 47(2):137-47. · 0.17 Impact Factor
  • Kyusam Choi, Hyunjeong Ju, Young Hyeh Ko
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    ABSTRACT: Copy number alteration was investigated in three cases of EBV + nodal peripheral T cell lymphoma of cytotoxic phenotype using Agilent array comparative genomic hybridization platform. While no recurrent abnormality among three cases was identified, genomic abnormalities involving 9p23.3, 16p13.3, and 7q34 were overlapped with changes reported in other type of NK or T cell lymphomas previously. Chromosomal region 9p23.3 contains CDKN2A and CDKN2B which are frequently mutated or deleted in various types of cancer and may be a target to find genes associated with the pathogenesis of EBV-positive nodal peripheral T cell lymphoma.
    Methods in molecular biology (Clifton, N.J.) 01/2013; 973:165-74. · 1.29 Impact Factor
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    ABSTRACT: Although human papillomavirus (HPV) infection is considered as a favorable prognostic factor in oropharyngeal cancer, the prognosis of HPV-associated tonsil cancer has rarely been studied especially when surgery was the main treatment. In this study, the authors investigated the effect of p16 over-expression (HPV infection) on tonsil cancer prognosis according to the type of treatment, HPV presence by PCR, and expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry (IHC). Medical records of 33 tonsil cancer patients were reviewed. Using formalin-fixed and paraffin-embedded tumor specimens, PCR-based genotyping of HPV and IHC of p16, p53 and EGFR were performed. The effects of HPV presence and the expression of IHC markers were analyzed on the recurrence-free survival. Five-year disease-free survival (DFS) rates were evaluated according to p16 expression status. An over-expression of p16 was observed in 27 (81.9%) out of 33 cases. Surgery-based treatment was provided for 21 (63.6%) patients. There was no association between p16 immunoreactivity and HPV presence, nor with p53 and EGFR expression. Regardless of main treatment modalities, five-year DFS did not differ by p16 expression status (P=0.051). However, over-expression of p16 was associated with a lower recurrence in multivariable analyses (P=0.046). Regardless of main treatment modalities, an over-expression of p16 (HPV infection) is associated with a lower recurrence in tonsil cancers. However it is not associated with simple HPV presence or p53 and EGFR over-expression.
    Clinical and Experimental Otorhinolaryngology 12/2012; 5(4):207-12. · 0.88 Impact Factor
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    ABSTRACT: Extranodal natural killer/T-cell lymphoma (ENKL) has a dismal prognosis. Although L-asparaginase has shown promising efficacy as a frontline therapy, currently there are no treatment options after progression to an L-asparaginase-containing regimen. We report the results of gemcitabine-containing therapy in patients with relapsed or refractory ENKL. We retrospectively reviewed 20 patients with refractory or relapsed ENKL who received a gemcitabine-containing regimen between 2005 and 2011. The overall response rate was 40 % (8 of 20 patients) with a complete response (CR) rate of 20 % (n = 4) and a partial response (PR) rate of 20 % (n = 4). Four complete responders had a disease-free status for more than 7 months including two patients received autologous stem cell transplantation consolidation and L-aspraginase maintenance, respectively. The median progression-free survival of the 20 patients was 2.3 months; however, it was 7.3 months for eight responders (CR and PR). The median overall survival of the eight responders had not been reached at the time of analysis. Gemcitabine was effective in a subset of pretreated ENKL patients and can be considered as a salvage option.
    Investigational New Drugs 10/2012; · 3.50 Impact Factor

Publication Stats

646 Citations
256.70 Total Impact Points

Institutions

  • 2002–2014
    • Sungkyunkwan University
      • • School of Medicine
      • • Department of Pathology
      • • Samsung Medical Center
      • • Department of Clinical Pathology
      • • Department of Radiology
      Sŏul, Seoul, South Korea
  • 2013
    • Samsung Medical Center
      Sŏul, Seoul, South Korea
  • 2011
    • Inje University Paik Hospital
      Sŏul, Seoul, South Korea
  • 2010
    • Gachon University
      • Department of Internal Medicine
      Seongnam, Gyeonggi, South Korea
  • 2008
    • Dong-A University
      • Department of Pathology
      Pusan, Busan, South Korea
  • 2006
    • Cheil General Hospital
      Sŏul, Seoul, South Korea
  • 2005
    • Konkuk University Medical Center
      Changnyeong, South Gyeongsang, South Korea