Hee Yun Seo

The Bone Morphogenesis Protein-2 (BMP-2) is Associated with Progression to Metastatic Disease in Gastric Cancer

PURPOSE Bone Morphogenetic Proteins (BMPs) are members of the TGF-beta superfamily and it has been demonstrated that BMPs enhance migration, invasion and metastasis. The purpose of this study was to identify the association between the serum BMP-2 level and the progression status of gastric cancer. MATERIALS AND METHODS Fifty-five patients with metastatic gastric cancer (metastatic disease group), six patients with early gastric cancer without lymph node metastasis (the EGC group), and ten healthy control subjects were enrolled in this study. The serum BMP-2 level was quantified by use of a commercially available ELISA kit. In EGC group patients and patients with metastatic disease, whole blood was obtained before endoscopic mucosal resection and before the commencement of a scheduled cycle of systemic chemotherapy, respectively. RESULTS No significant difference in the mean serum BMP-2 levels was observed between the control subjects and the EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p=1.0). However, the metastatic disease group patients had a significantly higher level of serum BMP (179.61 pg/ml) than the control subjects and EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p<0.0001). Moreover, the mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis (204.73 pg/ml versus 173.33 pg/ml, p=0.021). CONCLUSIONS BMP-2 seems to have a role in progression to metastatic disease in gastric cancer, especially in the late stage of tumorigenesis, including invasion and metastasis. BMP-2 may facilitate bone metastasis in gastric cancer. To confirm these findings, further studies are required with tissue specimens and the use of a cancer cell line.

Treatment outcome of front-line systemic chemotherapy for localized extranodal NK/T cell lymphoma in nasal and upper aerodigestive tract

We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 - 45.03] and 15.27 months (95% CI = 2.92 - 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 – 45.03] and 15.27 months (95% CI = 2.92 – 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.

Association study of TP53 polymorphisms with lung cancer in a Korean population

AbstractThe tumor suppressor gene, TP53, is located on chromosome 17p13.1 and is critical for DNA repair, cell-cycle control, and apoptosis. TP53 also plays a crucial function in the tumorigenesis of lung cancer. Inactivation of TP53 via genetic alterations such as missense mutations is often associated with lung cancer. In this study, potential association of TP53 polymorphisms with the risk of lung cancer was examined in a Korean population. A total of 299 Korean lung cancer patients and 296 control subjects were recruited into this study. Direct DNA sequencing and TaqMan analysis were employed, and logistic regression analyses were conducted to characterize the association between TP53 polymorphisms and lung cancer risk. Through direct sequencing in 24 Korean individuals, 13 sequence variants were identified, and five of these polymorphisms were selected for a larger-scale genotyping (n = 595). Statistical analyses revealed that polymorphisms and haplotypes in the TP53 gene, including Arg72Pro, were not significantly associated with lung cancer in a Korean population.

Reduced dose of imatinib for patients with chronic myeloid leukemia and low body surface area.

rean CML patients treated with a reduced dose of imatinib. Nine CML patients from the Korea University Hospital who were treated with a reduced dose of imatinib between March 2003 and September 2005 were reviewed retrospectively. All of the patients started the imatinib therapy with the recommended 400 mg/day dose. However, the imatinib dose was reduced to either 300 or 200 mg/day during the course of the treatment primarily due to drug toxicity. In patients who developed neutropenia 6 grade 3 or thrombocytopenia 6 grade 3, treatment was discontinued until neutrophils recovered to 6 1 ! 10 9 /l and/or platelets recovered to 6 50 ! 10 9 /l. Imatinib was then resumed at the same dose if the counts recovered within 2 weeks but was reduced to 300 mg daily if myelosuppression persisted for 6 2 weeks. If myelosuppression recurred, then imatinib was again discontinued, and imatinib was resumed at a dose of 300 mg daily. A complete response (CR) in hematologic parameters was defined as a WBC count ! 10 ! 10 9 /l, a platelet count

Prospective analysis of treatment outcome and prognostic factors in patients with T-cell lymphomas treated by CEOP-B: single institutional study

The important prognostic factors were evaluated for T‐cell non‐Hodgkin lymphoma (NHL) patients in a prospective study using the CEOP‐B protocol [a modified cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)‐like regimen that uses epirubicin instead of doxorubicin with the addition of bleomycin]. Fifty‐two patients were enrolled in the study. The overall response rate was 63·5%. The median progression‐free survival (PFS) and median overall survival (OS) was 18·0 and 39·5 months respectively. The most common toxicity was neutropenia. The factors related to poor outcome were a high International Prognostic Index (IPI) and a high ‘B’ score (bone marrow involvement, B symptoms, bulky disease). We developed a new prognostic model, namely the Prognostic Group for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2 (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly longer than those (11·5 and 4·8 months) in PGT2. The same result was observed in the PGT3 and PGT4 groups. The CEOP‐B regimen was moderately active and tolerable for T‐cell NHL patients, and the PGT system might be useful for the prediction of long‐term survival of T‐cell NHL patients.

The suggestion of a risk stratification system for febrile neutropenia in patients with hematologic disease

We analyzed the prognostic factors from 259 cases of febrile neutropenia occurring in 137 patients with hematologic disease. Based on multivariate analysis, significant prognostic factors are recovery of neutropenia, respiratory infection, baseline serum albumin, baseline bicarbonate, baseline CRP, and CRP on the fifth day after antibiotic treatment. From these variables, we derived a predictive model for the prognosis of febrile neutropenia using baseline serum albumin, bicarbonate, and CRP, which could be easily checked before chemotherapy. Further studies in prospective setting are needed for the validation of this model.

High-dose Immunoglobulin Infusion for Thrombotic Thrombocytopenic Purpura Refractory to Plasma Exchange and Steroid Therapy

The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

Clinical Factors Related to Suspected Second Primary Lung Cancer Development in Patients with Head and Neck Cancer.

PURPOSE The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC. MATERIALS AND METHODS We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006. RESULTS A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001). CONCLUSIONS Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

Epirubicin, cisplatin, oral UFT, and leucovorin combination chemotherapy in advanced and metastatic esophageal cancer

AbstractBackground: The purpose of treatment in patients with advanced and metastatic esophageal cancer is to improve symptoms and maintain quality of life. Recently, the regimen including epirubicin, cisplatin, and 5-FU (ECF) has been used with protracted venous infusion (PVI), and has been reported to be an effective treatment for advanced and metastatic csophagastric cancer. However, complications and the inconvenience associated with PVI cannot be justified for the treatment of advanced esophageal cancer. Therefore, we provided treatment with oral UFT and leucovorin instead of 5-FU PVI to improve convenience and catheter related complications. Patients and Methods: Thirty-seven patients with advanced esophageal cancer were admitted between March 2002 and April 2005. The treatment schedule was as follows: epirubicin 50 mg/m2 iv on d 1, cisplatin 60 mg/m2 iv on d 1, oral UFT 300 mg/m2 and leucovorin 75 mg for 21 consecutive days of treatment followed by a 7-d treatment-free interval. Results: The response rate was 45.9% including one complete response (95% CI: 29.8%–62%). The median survival was 13 mo (95% CI: 10–16 mo). Four patients had adenocarcinoma. Interestingly, their response rate was 75% including one complete response. Myelosuppression was the most important toxicity. Other toxicities were tolerable. Conclusion: The combination of epirubicin, cisplatin, UFT, and leucovorin (EPUL) could be another alternative to ECF in patients with advanced esophageal cancer. And this treatment might be more effective in adenocarcinoma of esophageal cancer.

Lack of association of fragile histidine triad (FHIT) polymorphisms with lung cancer in the Korean population

AbstractThe fragile histidine triad (FHIT), which was located on chromosome 3p14.2, was currently considered a promising candidate for a tumor suppressor gene. FHIT performed a crucial function in the tumorigenesis of lung cancer. The inactivation of FHIT via genetic alterations, including the chromosomal deletions and aberrant transcription, are often associated with lung cancer. In this study, the association between FHIT and lung cancer development was evaluated in a study of Korean patients. A total of 299 Korean lung cancer patients and 296 control subjects were recruited into this study. Direct DNA sequencing and TaqMan analysis were employed. Logistic regression analyses were conducted in order to characterize the association between FHIT polymorphisms and lung cancer risk. Via direct sequencing in 24 Korean individuals, 27 sequence variants were identified. Eleven of these polymorphisms were selected for a larger scale genotyping (n = 595). Our finding indicated that the polymorphisms and haplotypes in the FHIT gene are not associated with lung cancer in the Korean population.