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1.  Epstein-Barr Virus-Positivity in Tumor has no Correlation with the Clinical Outcomes of Patients with Angioimmunoblastic T-cell Lymphoma 
Background/Aims
Epstein-Barr virus (EBV) is involved in the pathogenesis of angioimmunoblastic T-cell lymphoma (AILT), but its precise role and prognostic impact are not clear. This study aimed to evaluate the incidence of EBV-postitivity in the tumor and bone marrow (BM) samples from AILT patients, and their correlations with the clinical variables and patient survival.
Methods
Seventy AILT cases were identified over a period of 8 years. Twenty seven cases were investigated for their EBV tumor status, and 10 BM samples of these patients were investigated for their EBV status with using in situ hybridization (ISH). EBV PCR was performed for the BM mononuclear cells in 8 cases.
Results
Among the 27 tumor specimens, ten (37%) were EBV-positive. Only CD20-negativity in tumor correlated with the EBV-positivity (p=0.035). In 13 (48%) patients, gross tumor involvement was recognized by hematoxylin-eosin staining at the time of diagnosis. Among the 10 patients who had additional BM slides available, there were 3 with BM involvement, and none showed EBV positive results on ISH. EBV PCR of the BM mononuclear cells revealed one-positive case among 8 patients. This patient was negative for both BM involvement and EBV ISH. The median overall survival of the 25 treated patients was 48.9 months (95% CI: 18.6~79.2 months). Neither overall survival nor progression-free survival was related with EBV-positivity of the tumor.
Conclusions
EBV-positivity of tumor had no impact on the prognosis of AILT patients.
doi:10.3904/kjim.2008.23.1.30
PMCID: PMC2686953  PMID: 18363277
Epstein-Barr virus; Angioimmunoblastic T-cell lymphoma; Survival
2.  Immune thrombocytopenic purpura in a patient with renal cell carcinoma 
doi:10.3904/kjim.2014.29.5.671
PMCID: PMC4164733  PMID: 25228845
Carcinoma, renal cell; Paraneoplastic syndromes; Purpura, thrombocytopenic, idiopathic
3.  Prevention of Venous Thromboembolism, 2nd Edition: Korean Society of Thrombosis and Hemostasis Evidence-Based Clinical Practice Guidelines 
Journal of Korean Medical Science  2014;29(2):164-171.
In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.
Graphical Abstract
doi:10.3346/jkms.2014.29.2.164
PMCID: PMC3923992  PMID: 24550640
Guideline; Prevention; Venous Thromboembolism; Bleeding
4.  Prevalence and Risk Factors for Iron Deficiency Anemia in the Korean Population: Results of the Fifth Korea National Health and Nutrition Examination Survey 
Journal of Korean Medical Science  2014;29(2):224-229.
This study assessed the prevalence of, and risk factors for, iron deficiency (ID) and iron deficiency anemia (IDA) among participants of the fifth Korean Health and Nutrition Examination Survey, 2010. Of 8,958 participants, 6,758 individuals ≥10 yr had sufficient data for the analysis of anemia and iron status. ID was defined as a transferrin saturation <10% or serum ferritin <15 µg/L. The prevalence of ID and IDA was 2.0% (95% confidence interval [CI], 1.3%-2.6%) and 0.7% (95% CI, 0.3%-1.0%), respectively, in males, and 22.4% (95% CI, 20.7%-24.2%) and 8.0% (95% CI, 6.8%-9.2%), respectively, in females. In reproductive age females, the prevalence of ID and IDA was 31.4% (95% CI, 28.9%-33.8%) and 11.5% (95% CI, 9.6%-13.4%), respectively. Compared to the prevalence of IDA in adult males 18-49 yr, the relative risks of IDA in adults ≥65 yr, lactating females, premenopausal females, and pregnant females were 8.1, 35.7, 42.8, and 95.5, respectively. Low income, underweight, iron- or vitamin C-poor diets were also associated with IDA. For populations with defined risk factors in terms of age, gender, physiological state and socioeconomic and nutritional status, national health policy to reduce IDA is needed.
Graphical Abstract
doi:10.3346/jkms.2014.29.2.224
PMCID: PMC3924001  PMID: 24550649
Anemia, Iron Deficiency; Korea
5.  A Combination of Melphalan, Prednisone, and 50 mg Thalidomide Treatment in Non-Transplant-Candidate Patients with Newly Diagnosed Multiple Myeloma 
Background/Aims
The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a first-line treatment. Because the side effects of thalidomide at a dose of ≥ 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates.
Methods
Twenty-one patients were treated in 4-week cycles, receiving 4 mg/m2 melphalan and 40 mg/m2 prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism.
Results
The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy.
Conclusions
Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.
doi:10.3904/kjim.2011.26.4.403
PMCID: PMC3245388  PMID: 22205840
Multiple myeloma; Thalidomide; Melphalan; Prednisone
6.  Korean Patients with Superwarfarin Intoxication and Their Outcome 
Journal of Korean Medical Science  2010;25(12):1754-1758.
This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.
doi:10.3346/jkms.2010.25.12.1754
PMCID: PMC2995229  PMID: 21165290
Superwarfarin; Brodifacoum; Vitamin K; Rodenticides
7.  Korean Guidelines for the Prevention of Venous Thromboembolism 
Journal of Korean Medical Science  2010;25(11):1553-1559.
This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.
doi:10.3346/jkms.2010.25.11.1553
PMCID: PMC2966990  PMID: 21060742
Guideline; Prevention; Venous Thromboembolism
8.  Is RARS-T a new disease entity or a subtype of RARS or ET? 
The Korean Journal of Hematology  2010;45(2):139-140.
doi:10.5045/kjh.2010.45.2.139
PMCID: PMC2983031  PMID: 21120195
9.  Severe Pulmonary Adverse Effects in Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) Regimen Plus Rituximab 
Background/Aims
The aim of our study was to determine the incidence and clinical features of severe pulmonary complications in patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) as the initial treatment for lymphoma.
Methods
A retrospective analysis of pulmonary infection and drug-induced interstitial pneumonitis (DIIP) was performed using lymphoma registry data. R-CHOP was administered in 71 patients and CHOP in 29 patients.
Results
The severe pulmonary adverse events tended to occur more frequently with R-CHOP (18.3%) than CHOP alone (13.8%), although the difference was not significant (p = 0.771). DIIP occurred in five patients in the R-CHOP arm (7%) and in one in the CHOP arm (3%). The continuous use of steroids for conditions other than lymphoma significantly increased the risk of pulmonary infection including Pneumocystis jiroveci pneumonia (p = 0.036) in the multivariate analysis. International prognostic index, tumor stage, smoking, previous tuberculosis, chronic obstructive pulmonary disease, and lymphoma involvement of lung parenchyma were not related to pulmonary adverse events. Patients who experienced severe pulmonary events showed shorter survival when compared to those without complications (p = 0.002).
Conclusions
Our experiences with serial cases with DIIP during chemotherapy and the correlation of continuous steroid use with pulmonary infection suggest that the incidence of pulmonary complications might be high during lymphoma treatment, and careful monitoring should be performed.
doi:10.3904/kjim.2010.25.1.86
PMCID: PMC2829422  PMID: 20195409
Rituximab; Drug therapy; Lymphoma, non-Hodgkin; Adverse effects; Lung diseases, interstitial
10.  Castleman Disease Presenting with Jaundice: A Case with the Multicentric Hyaline Vascular Variant 
Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology with different clinical manifestations. A previous healthy 50 year-old man was hospitalized for right upper quadrant (RUQ) abdominal pain. He had jaundice and a 1 cm-sized lymph node in the right supraclavicular area. Pancreas and biliary computed tomography (CT) showed masses at the right renal hilum and peripancreatic areas. Positron emission tomography (PET) showed widespread systemic lymphadenopathy. Excisional biopsy of the right supraclavicular node revealed a hyaline vascular variant of CD. Corticosteroid therapy was started and the extent of disease decreased. We here report a case of multicentric CD, the hyaline vascular variant, presenting with jaundice, diagnosed by excisional biopsy and successfully treated with corticosteroids.
doi:10.3904/kjim.2007.22.2.113
PMCID: PMC2687612  PMID: 17616028
Lymphoproliferative Disorder; Jaundice; Obstructive; Castleman Disease
11.  Diagnostic Usefulness of the Janus Kinase 2 Mutation in non BCR/ABL Myeloproliferative Disorders 
Background
We investigated the Janus kinase 2 (JAK2) mutation and its diagnostic value in patients suffering with non BCR/ABL myeloproliferative diseases (nMPD) or other reactive conditions.
Methods
We reviewed the clinical records of 83 patients who underwent bone marrow (BM) examinations with suspect of nMPD. The diagnoses of nMPD were made based on the WHO criteria since 2001 and the PVSG criteria before 2001. The JAK2 mutation was examined by PCR in 54 patients whose BM samples were available.
Results
The JAK2 mutation was detected in 25 patients (46%); 12 of 26 patients with essential thrombocythemia (ET), 9 of 12 patients with polycyhtemia vera (PV), one of 7 patients with chronic idiopathic myelofibrosis (CIM) and one patient with unclassifiable MPD. Additionally, JAK2 mutation was detected in each one patient with secondary polycythemia and reactive thrombocytosis. These two patients and two other patients among the JAK2 mutated ET did not meet the WHO PV criteria due to their initial low hemoglobin levels. These patients had liver cirrhosis and hypersplenism due to Budd-Chiari syndrome (1), gastrointestinal bleeding (1) or the initial hemoglobin level was slightly below the level as provided by the criteria, but the level showed a rising pattern despite cytoreductive therapy (2). With the results of the JAK2 mutation available, 4 patients' disease could be re-diagnosed as PV. Finally, the positive rate of the JAK2 mutation was 81% in PV, 48% in ET and 14% in CIM. The presence of JAK2 mutation closely correlated with PV (p=0.001), leukocytosis (p=0.001) and an increased cellularity of BM (p=0.024).
Conclusions
The JAK2 mutation may help differentiate nMPD from secondary cytosis. Therefore, it should be incorporated into the guidelines for the nMPD work-up for making a more accurate diagnosis and administering proper treatment.
doi:10.3904/kjim.2006.21.4.219
PMCID: PMC3891025  PMID: 17249502
Janus kinase 2 mutation; Myeloproliferative disorders; Polycythemia vera; Essential thrombocythemia; Chronic idiopathic myelofibrosis
12.  Two Cases of Interstitial Pneumonitis Caused by Rituximab Therapy 
Rituximab, a chimeric monoclonal antibody directed against CD20, has become a part of the standard therapy for patients with non-Hodgkin's lymphoma either in combination with other drugs or as a single agent. The CD20 antigen is expressed on 95% of B-cell lymphoma cells and normal B-cells but, is not found on precursor B-cells or stem cells. Rituximab is now approved for patients with diffuse large B-cell lymphoma when combined with standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) or patients with follicular lymphoma who have failed first line chemotherapy. The monoclonal antibody is generally well tolerated. Most of the adverse events are infusion-associated, mild to moderate non-hematological toxicities. Severe respiratory adverse events have been infrequent. Here, we report two patients with non-Hodgkin's lymphoma in whom interstitial pneumonitis developed with rituximab therapy.
doi:10.3904/kjim.2006.21.3.183
PMCID: PMC3890722  PMID: 17017668
Rituximab; Non-Hodgkin's lymphoma; Diffuse large B-cell lymphoma; Follicular lymphoma; Interstitial pneumonitis
13.  Neutrophilic Myositis without Cutaneous Involvement as the First Manifestation of Acute Myeloid Leukemia 
Muscle involvement in acute febrile neutrophilic dermatosis is uncommon. Herein, we report a case of acute febrile neutrophilic myositis, without cutaneous involvement, as the first manifestation of acute myeloid leukemia. The patient was a 35-year-old male, referred due to painful swelling of the left upper arm and fever. The overlying skin looked normal, and a muscle biopsy revealed dense infiltrates, predominantly composed of mature neutrophils, edema and tissue necrosis. All culture reports were negative, and he was finally diagnosed as having acute febrile neutrophilic myositis, associated with acute myeloid leukemia. Corticosteroid treatment resulted in the progressive regression of the fever, myalgia and swelling.
doi:10.3904/kjim.2005.20.4.346
PMCID: PMC3891084  PMID: 16491836
Acute febrile neutrophilic dermatosis; Myositis; Acute myeloid leukemia
14.  Clinical Factors Associated with Response or Survival after Chemotherapy in Patients with Waldenström Macroglobulinemia in Korea 
BioMed Research International  2014;2014:253243.
Waldenström's macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n = 71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37–92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%, P = 0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73–111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM.
doi:10.1155/2014/253243
PMCID: PMC4065725  PMID: 24995279
15.  Direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism 
Blood research  2014;49(2):77-79.
doi:10.5045/br.2014.49.2.77
PMCID: PMC4090339  PMID: 25025005
17.  A Prospective Study on the Incidence of Postoperative Venous Thromboembolism in Korean Gastric Cancer Patients: An Inquiry into the Application of Western Guidelines to Asian Cancer Patients 
PLoS ONE  2013;8(4):e61968.
Several Western guidelines recommend the routine use of pharmacologic thromboprophylaxis for cancer surgery patients to prevent venous thromboembolism (VTE). However, the necessity of routine pharmacologic perioperative thromboprophylaxis in Asian gastric cancer (GC) patients has not been clearly determined. To determine the necessity of routine perioperative pharmacologic thromboprophylaxis in Korean gastric cancer patients, the incidence of postoperative VTE was prospectively evaluated in gastric cancer patients receiving surgery. Among 610 GC patients who had received surgery, 375 patents underwent routine duplex Doppler ultrasonography (DUS) on days 5–12 following surgery to detect VTE and then VTE-related symptoms and signs were checked at 4 weeks after surgery (cohort A). The 235 patients that declined DUS were registered to cohort B and the occurrence of postoperative VTE was retrospectively analyzed. In cohort A, symptomatic or asymptomatic VTE until 4 weeks after surgery was detected in 9 patients [2.4%; 95% confidence interval (CI); 0.9–3.9]. Tumor stage was a significant factor related to VTE development [stage I, 1.4%; stage II/III, 2.4%; stage IV, 9.7% (P = 0.008)]. In multivariate analysis, patients with stage IV had a higher postoperative VTE development [odds ratio, 8.18 (95% CI, 1.54–43.42)] than those with stage I. In cohort B, a low incidence of postoperative VTE was reaffirmed; only one postoperative VTE case (0.4%) was observed. In conclusion, the incidence of postoperative VTE in Korean GC patients was only 2.4%. Risk-stratified applications of perioperative pharmacologic thromboprophylaxis are thought to be more appropriate than the routine pharmacologic thromboprophylaxis in Korean GC patients receiving surgery.
doi:10.1371/journal.pone.0061968
PMCID: PMC3629116  PMID: 23613988
18.  Targeting the protein kinases for anti-cancer therapy 
The Korean Journal of Hematology  2012;47(3):157-158.
doi:10.5045/kjh.2012.47.3.157
PMCID: PMC3464329  PMID: 23071467
19.  Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer 
BMC Cancer  2012;12:347.
Background
We evaluated the association between a KRAS mutational status and various clinicopathologic features including the metastatic pattern in patients with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed.
Methods
The KRAS mutational status in codons 12, 13, and 61 from formalin-fixed sections of both primary tumors and related metastases was determined by sequencing analysis. One hundred forty-three Korean patients with MRCRC with available tissues (resection or biopsy) from both primary tumors and related metastatic sites were consecutively enrolled.
Results
The KRAS mutation rate was 52.4% (75/143) when considering both the primary and metastatic sites. When the relationship between the KRAS status and initial metastatic sites at the time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the initial metastatic site in patients with the KRAS mutation than in patients without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs. 70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025) were less frequent as the initial metastatic organ in patients with the KRAS mutation than in patients without the KRAS mutation. The discordance rate of KRAS mutational status between primary and paired metastatic sites other than the lung was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate was significantly higher in matched lung metastases [32.4% (12/37)] than in other matched metastatic organs (P = 0.005).
Conclusions
Organs initially involved by distant metastasis were different according to the KRAS mutational status in MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at metastatic sites other than the lung was generally high compared with primary tumor sites; however, lung metastasis had a high rate of KRAS discordance (32.4%).
doi:10.1186/1471-2407-12-347
PMCID: PMC3488475  PMID: 22876814
KRAS mutation; Lung metastasis; Discordance; Colorectal cancer
20.  Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive immunoglobulin M anti-hepatitis E virus: a case report 
The Korean Journal of Hepatology  2011;17(4):323-327.
A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.
doi:10.3350/kjhep.2011.17.4.323
PMCID: PMC3304669  PMID: 22310798
Hepatitis A virus; Genotype; Coinfection; Hemolytic anemia; Korea
21.  Tumor Burden Assessed by the Maximum Standardized Uptake Value and Greatest Diameter on FDG-PET Predicts Prognosis in Untreated Diffuse Large B-cell Lymphoma 
Purpose
It is uncertain whether the tumor burden as assessed using FDG-PET has prognostic significance in newly diagnosed diffuse large B-cell lymphoma (DLBCL). The authors undertook this study to determine whether a parameter that reflects both FDG uptake magnitude and the greatest tumor diameter is a prognostic indicator in DLBCL.
Materials and Methods
Forty-two DLBCL patients (age, 57.4 ± 15.5 years; male/female = 25/17; stage I/II/III/IV=5/17/10/10) who underwent FDG-PET before chemotherapy were enrolled. A lesion with the highest maximum standardized uptake value (MaxSUV) on the PET image was selected, and size-incorporated MaxSUV (SIMaxSUV) of mass was calculated as MaxSUV × greatest diameter (mm) on the transaxial PET image. Median follow-up duration was 20.0 months.
Results
Twelve (28.6% = 12/42) patients experienced disease progression, and 10 (23.8% = 10/42) died during follow-up. Among six variables [Ann Arbor stage, %Ki-67 expression, International Prognostic Index (IPI), MaxSUV, greatest diameter, and SIMaxSUV] investigated, only SIMaxSUV was found to be a single determinant of progression-free and overall survivals by multivariate analyses (p < 0.05).
Conclusion
These results suggest that SIMaxSUV, a new FDG-PET parameter that incorporates FDG uptake magnitude and the greatest tumor diameter, may be a useful indicator of prognosis in untreated DLBCL.
doi:10.1007/s13139-009-0009-0
PMCID: PMC4042962  PMID: 24899936
FDG-PET; Lymphoma; Prognosis; SUV; Size-incorporated maxSUV; Greatest diameter
22.  Cisplatin-Based Combination Chemotherapy for Advanced Hepatocellular Carcinoma: A Single Center Experience before the Sorafenib Era 
Purpose
Systemic chemotherapy is the only option for patients with unresectable/metastatic hepatocellular carcinoma (HCC) who are not candidates for local/regional treatment. However, the response to such treatment and survival are poor, especially in hepatitis B virus (HBV) endemic areas. The aim of this study was to determine the efficacy of cisplatin-based combination chemotherapy and identify a subgroup of advanced HCC patients with favorable responses.
Materials and Methods
The medical records of all consecutive patients with unresectable/metastatic HCC who received cisplatin-based combination chemotherapy between January 2003 and October 2009 were reviewed. Time to progression (TTP) and overall survival (OS) were determined using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify prognostic factors for TTP and OS.
Results
Data for 46 patients were analyzed. First-line chemotherapies consisted of cisplatin-based combination treatment with doxorubicin, fluoropyrimidines and gemcitabine. The response rate for all patients was 4.3%. The median TTP and OS were 1.8 (95%confidence interval [CI], 1.1 to 2.5) and 7.2 (95% CI, 3.0 to 11.5) months, respectively. Eastern Cooperative Oncology Group (ECOG) performance status (PS), Child classification, Cancer of the Liver Italian Program (CLIP) score and portal vein thrombosis (PVT) were identified by univariate analyses as prognostic factors for TTP and OS. ECOG PS (hazard ratio [HR], 4.51; 95% CI, 1.61 to 12.6; p=0.004) and PVT (HR, 2.12; 95% CI, 1.10 to 4.11; p=0.026) were independent prognostic factors for TTP.
Conclusion
Cisplatin-based combination chemotherapy in patients with advanced HCC has a low response rate and short TTP regardless of the chemotherapy regimen used. Patients with a good ECOG PS and without PVT can be considered candidates for cisplatin-based combination chemotherapy.
doi:10.4143/crt.2010.42.4.203
PMCID: PMC3021739  PMID: 21253322
Hepatocellular carcinoma; Platinum; Prognosis; Chemotherapy; Survival
23.  Cost Analysis of Iron-Related Complications in a Single Institute 
Background/Aims
The financial burden of caring for iron-related complications (IRCs) is an emerging medical problem in Korea, as in Western countries. We produced a preliminary estimate of the costs of treating patients for IRCs.
Methods
The medical records of patients who had received multiple transfusions were reviewed. Newly developed cardiomyopathy, heart failure, diabetes mellitus, liver cirrhosis, and liver cancer were defined as IRCs. The costs of laboratory studies, medication, oxygenation, intervention, and education were calculated using working criteria we defined. Costs that had a definite causal relationship with IRCs were included to produce as accurate an estimate as possible.
Results
Between 2002 and 2006, 650 patients with hematologic diseases, including 358 with acute leukemia, 102 with lymphoma, 58 with myelodysplastic syndrome or myeloproliferative disease, 46 with multiple myeloma, and 31 with chronic leukemia, received more than 10 units of red blood cells. Nine patients developed IRCs. The primary diagnoses of eight patients were aplastic anemia and that of one patient was chronic lymphocytic leukemia. Two patients who had diabetes were excluded because one was treated at another hospital and the other was diagnosed as oxymetholone-induced diabetes. Of the seven patients included, liver cirrhosis developed in two, heart failure in four, and diabetes mellitus in three. Some of them had two diagnoses. The total cost attributed to IRCs for the seven patients was 47,388,241 KRW (approximately 50,000 USD).
Conclusions
The medical costs of IRCs are considerable, and more effective iron-chelating therapy is necessary to save medical resources and improve patient care. More in the way of comprehensive health and economic studies of IRCs are needed to allow both clinicians and health-policy makers to make better decisions.
doi:10.3904/kjim.2009.24.1.33
PMCID: PMC2687652  PMID: 19270479
Iron overload; Costs and cost analysis
24.  Low Frequency and Variability of FLT3 Mutations in Korean Patients with Acute Myeloid Leukemia 
Journal of Korean Medical Science  2008;23(5):833-837.
FLT3 mutations are common genetic changes, and are reported to have prognostic significance in acute myeloid leukemia (AML). The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up. There were 226 patients with AML enrolled between March 1996 and August 2005. The incidence of ITD and TKD at diagnosis was 13% (29/226) and 3% (6/226). When compared to Western and other Asian patients with AML, Korean patients had a lower frequency by about two-thirds of ITD and TKD. Among the non-M3 cases (N=203), the patients with an ITD had a significantly shorter event-free survival when compared with those without an ITD (p=0.0079). Among 54 relapsed patients, 9 patients had the FLT3 ITD at diagnosis. Six patients demonstrated a reappearance of the ITD and 3 patients remained negative at relapse. One patient, among 45 patients who relapsed, had a negative baseline ITD but acquired a de novo ITD at relapse. There were 101 samples from 93 patients in remission; they were all negative for an ITD. Among 34 patients who failed to achieve a remission, five patients had a persistent ITD and one patient had a de novo ITD. These results support the concept of resistance of FLT3 ITD leukemic clones to chemotherapy. Therefore, effective therapy with FLT3 targeting agents may improve the prognosis of non-M3 AML patients with the FLT3 mutation.
doi:10.3346/jkms.2008.23.5.833
PMCID: PMC2580007  PMID: 18955790
FLT3 Mutations; Internal Tandem Duplication; Tyrosine Kinase Domain Mutation; Leukemia, Myeloid, Acute
25.  Thalidomide for Treating Metastatic Hepatocellular Carcinoma: A Pilot Study 
Background
Thalidomide has been reported to have antitumor activity for treating metastatic hepatocellular carcinoma (HCC). We evaluated the safety and efficacy of using thalidomide for treating selected patients with unresectable or metastatic HCC, and their disease was refractory to systemic chemotherapy.
Methods
Eight patients with measurable and metastatic HCC that had progressed with prior systemic chemotherapy and who desired further active therapy were enrolled in this study. Thalidomide was given orally at bedtime and it was started at 200 mg/day with no further dose escalation. The response was measured at 2-month intervals.
Results
The median age was 44 years (range: 34-52 years) and all the patients had received doxorubicin-based systemic chemotherapy prior to their enrollment. Each patient received thalidomide for a median of 152 days (range: 5-422 days). One partial response was observed (12.5%, 95% CI; 0-42%) along with 4 cases of stable diseases. The most commonly encountered toxicity was somnolence; grade 3 somnolence was noted for one patient, which led to treatment discontinuation. Skin rash was observed in one responding patient.
Conclusions
The results indicate that thalidomide may feasibly offer disease stabilization to metastatic HCC patients. Further dose escalation of thalidomide, or its combination with other chemotherapeutic agents, may be of interest and this should be investigated for treating patients with metastatic HCC.
doi:10.3904/kjim.2006.21.4.225
PMCID: PMC3891026  PMID: 17249503
Carcinoma; Hepatocellular; Thalidomide

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