Purpose: Pneumococcal vaccination (13-valent pneumococcal conjugate vaccine [PCV13]) is recommended to cancer patients undergoing systemic chemotherapy. However, the optimal time interval between vaccine administration and initiation of chemotherapy has been little studied in adult patients with solid malignancies. Materials and Methods: We conducted a prospective randomized controlled trial to evaluate whether administering PCV13 on the first day of chemotherapy is non-inferior to vaccinating 2 weeks prior to chemotherapy initiation. Patients were randomly assigned to two study arms, and serum samples were collected at baseline and 4 weeks after vaccination to analyze the serologic response against Streptococcus pneumoniae using a multiplexed opsonophagocytic killingassay. Results: Of the 92 patients who underwent randomization, 43 patients in arm A (vaccination 2 weeks before chemotherapy) and 44 patients in arm B (vaccination on the first day of chemotherapy) were analyzed. Immunogenicity was assessed by geometric mean and fold-increase of post-vaccination titers, seroprotection rates (percentage of patients with post-vaccination titers > 1:64), and seroconversion rates (percentage of patients with > 4-fold increase in post-vaccination titers). Serologic responses to PCV13 did not differ significantly between the two study arms according to all three types of assessments. Conclusion The overall antibody response to PCV13 is adequate in patients with gastric and colorectal cancer during adjuvant chemotherapy, and no significant difference was found when patients were vaccinated two weeks before or on the day of chemotherapy initiation.

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.
Disease-Free Survival ; Drug Therapy* ; Drug Therapy, Combination ; Global Health ; Humans ; Korea ; Observational Study ; Prospective Studies ; Quality of Life* ; Stomach Neoplasms* ; Weights and Measures

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.
beta Catenin ; Cytoplasm ; Disease-Free Survival ; Epstein-Barr Virus Infections ; Humans ; Immunohistochemistry ; Lymph Nodes ; Membranes ; Multivariate Analysis ; Neoplasm Metastasis ; RNA ; Stomach Neoplasms ; Tumor Suppressor Protein p53

The present study analyzed the prognostic impact of MET gene copy number in patients with curatively resected gastric cancer who received a combination regimen of cisplatin and S-1. The MET gene copy number was analyzed by use of quantitative real-time polymerase chain reaction. From January 2006 to July 2010, 70 tumor samples from 74 patients enrolled in a pilot study were analyzed. According to a cutoff MET gene copy number of > or =2 copies, a high MET gene copy number was observed in 38 patients (54.3%). The characteristics of the 2 groups divided according to MET gene copy number were similar. With a median follow-up duration of 26.4 months (range, 2.6-73.2 months), the estimated 3-year relapse-free survival and overall survival rates were 54.3% and 77.4%, respectively. No significant association was observed between the MET gene copy number and survival in a multivariate analysis. The MET gene copy number investigated in this study was not found to be associated with prognosis in patients with curatively resected gastric cancer.
Chemotherapy, Adjuvant ; Cisplatin ; Follow-Up Studies ; Gene Dosage ; Humans ; Multivariate Analysis ; Pilot Projects ; Prognosis ; Real-Time Polymerase Chain Reaction ; Stomach Neoplasms ; Survival Rate

PURPOSE: Insulin-like growth factors (IGFs) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with gastrointestinal stromal tumors (GISTs). METHODS: Two hundred-thirteen consecutive patients with GISTs who underwent curative surgery from 5 medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four IGF-1 (+2995C/A, +533C/T, IVS2-16540A/G, Ex4-177G/C) and one IGF-2 (IVS1+1280A/G) gene polymorphisms were determined using a Sequenom MassARRAY system. RESULTS: With a median follow-up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 69.9% and 86.7%, respectively. In a multivariate analysis including age, gender, primary site of disease, pathology, and risk stratification, no significant association was observed between the polymorphism of the IGF-1 and IGF-2 genes and survival. CONCLUSION: None of the five IGF-1 and IGF-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of IGF-1 and IGF-2 gene polymorphisms as a prognostic biomarker for GIST patients.
Apoptosis ; Cell Proliferation ; DNA ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; Humans ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Prognosis ; Somatomedins ; Survival Rate

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis. METHODS: We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues. RESULTS: Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11. CONCLUSIONS: Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.
DNA ; Exons ; Gastrointestinal Stromal Tumors ; Gastrointestinal Tract ; Immunohistochemistry ; Paraffin ; Protein Kinases ; Receptors, Platelet-Derived Growth Factor ; Sequence Analysis

PURPOSE: Although the vascular endothelial growth factor (VEGF) superfamily has been identified to critically influence tumor-related angiogenesis, the prognostic significance of a VEGF expression in gastric cancer is still controversial. Accordingly, the present study analyzed the VEGF-A and VEGF-C expressions and their impact on the prognosis of patients with gastric cancer. MATERIALS AND METHODS: Three hundred seventy-five consecutive patients who underwent surgical resection for gastric adenocarcinoma with a curative intent were enrolled in the present study. Immunohistochemical staining for VEGF-A and VEGF-C was performed using the formalin fixed, paraffin embedded tumor tissues. RESULTS: Positive VEGF-A and VEGF-C expressions were observed in 337 (90.1%) and 278 (74.9%) cases, respectively. The survival analysis showed that the expression of VEGF-A and VEGF-C had no effect on the OS and DFS. On the multivariate analysis that included age, gender and the TNM stage, no significant association between the grade of the VEGF-A or VEGF-C expression and survival was observed. CONCLUSION: The current study suggests that the tissue expression of VEGF-A or VEGF-C alone is not an independent prognostic marker for patients with surgically resected gastric adenocarcinoma.
Adenocarcinoma ; Formaldehyde ; Humans ; Multivariate Analysis ; Paraffin ; Prognosis ; Stomach Neoplasms ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C

BACKGROUND: A primary central nervous system lymphoma (PCNSL) is a rare neoplasm with a poor prognosis. The treatment of PCNSL involves a combination of chemotherapy, intrathecal chemotherapy and radiotherapy. This study retrospectively evaluated the treatment outcomes and prognostic factors of Korean patients with PCNSL. METHODS: Between 1995 and 2003, 58 patients diagnosed with PCNSL from the multi-center hospitals were enrolled in this study. Among 56 patients who had received treatment, 16 patients were treated with radiotherapy alone, while 40 patients were treated with combined chemotherapy (CHOP; 9 cases, high-dose methotrexate; 31 cases) and radiotherapy. RESULTS: The median age of the patients was 58 years (range, 19-76). A diffuse large B-cell lymphoma was diagnosed in 56 cases (96.6%), while a peripheral T-cell lymphoma was diagnosed in 2 cases. Of the 47 patients who could be assessed for their response after treatment, a CR and PR was observed in 32 (68%) and 11 patients (23%), respectively, giving an overall response rate of 91% (95% CI, 82~100%). The estimated 3-year overall survival rate for all the patients was 67+/-7.9% and the 3-year disease free survival rate was 53+/-8.3%. The overall survival of the high-dose methotrexate group was superior to that of the CHOP group (77+/-10% versus 47+/-19%, p=0.05). Leukoencephalopathy was observed as a late complication in 9 patients (21%). No significant prognostic factors affecting survival were found by univariate analysis. CONCLUSIONS: Approximately half of the patients could have long-term survival after treatment in this study. High-dose methotrexate containing chemotherapy followed by radiotherapy was found to be an effective treatment.
Central Nervous System* ; Disease-Free Survival ; Drug Therapy ; Humans ; Leukoencephalopathies ; Lymphoma* ; Lymphoma, B-Cell ; Lymphoma, T-Cell, Peripheral ; Methotrexate ; Prognosis ; Radiotherapy ; Retrospective Studies* ; Survival Rate

OBJECTIVES: Although genotype of endothelial nitric oxide synthase has been investigated in many neuropsychiatric disorders, results were controversial and even contradictory. The purpose of this study was to investigate the nature of endothelial nitric oxide synthase in Korean schizophrenic patients, and compare it with healthy control group in terms of distribution of e genotype and allele frequency of endothelial nitric oxide synthase. METHODS: Using polymerase chain reaction and amplified refractory mutation system, endothelial nitric oxide synthase genotypes were identified in 77 schizophrenics and 121 healthy controls. RESULTS: 1) When genotypes of endothelial nitric oxide synthase were classified as a/a, a/b, b/b, there was no statistical difference in genotypes between the two groups. 2) In terms of allele frequency, there was also no statistical difference between the two groups. CONCLUSION: These results suggest that endothelial nitric oxide synthase gene seem to be unrelated to the pathogenesis of schizophrenia in Korean population.
Gene Frequency ; Genotype ; Humans ; Nitric Oxide Synthase Type III* ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Schizophrenia

BACKGROUND: In combination with standard-dose CHOP (cyclophosphamide, vincristine, adriamycin, and prednisolone), the addition of rituximab produces a better clinical response in the treatment of aggressive B-cell non-Hodgkin's lymphoma (NHL) than CHOP alone. METHODS: Thirty-four patients with previously untreated diffuse large B-cell NHL received at least three or four cycles of rituximab 375 mg/m2 or 500 mg per dose on day 1 of each cycle in combination with CHOP chemotherapy. RESULTS: The median age of patients were 61.5 years (range, 28-83 years). After the end of therapy, twenty-five patients (73.5%) experienced a complete response, four patients (11.8 %) had a partial response, and two patients (5.9%) were classified as having progressive disease. The median follow-up duration was 9.4 months (range, 0.2-19.5 months) and 1-year overall survival and progression free survival was 84.8+/-8.7% and 80.3+/-9.4%, respectively. Two patients (5.9%) experienced fever, myalgia, and skin eruption due to rituximab. Neutropenia of grade 3 or 4 occurred in thirty-one patients (91.2%). CONCLUSION: The benefits of rituximab in combination with CHOP chemotherapy include high response rates and good tolerance. However, further prospective, randomized studies are needed to draw definitive conclusions.
B-Lymphocytes* ; Disease-Free Survival ; Doxorubicin ; Drug Therapy* ; Fever ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell* ; Lymphoma, Non-Hodgkin ; Myalgia ; Neutropenia ; Skin ; Vincristine ; Rituximab