거대적아구성빈혈의 임상적 고찰

곽승근,천재민,박남숙,박상은,박수진,윤환중,김삼용,조덕연 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Megaloblastic anemias are disorders caused by impaired DNA synthesis and chara-cterized by the presence of megaloblastic cells. Clinical data on these disorders in Korea are limited. The aim of this study was to analyze clinical characteristics of megaloblastic anemias caused by vitamin B12 deficiency. We identified 40 cases who were diagnosed as megaloblastic anemia from January 1993 to December 2002 in a retrospective study on the basis of chart review. We investigated the annual distribution of diagnosed patients, clinical manifestations and response to treatment. 19 cases were complicated with a previous total gastrectomy(gastrectomy group) and 21 cases had no history of surgical operation(non-gastrectomy group). The most common presenting complaint was generalized weakness. The median age at diagnosis was 7(range: 38-79) years in non-gastrectomy group. The mean pos-toperative duration was 7(range: 4-25)years in group of total gastrectomy and mean level of serum vitamin B12 was lower than 100 pg/mL in both group. Peripheral blood revealed thrombocy-topenia, macrocytic anemia and hypersegmented neutrophil in all cases. After treatment of pareliteral vitamin B12, Their clinical symptoms and hematologic findings improved except two patients who had bone marrow with lower cellularity. Cobalamin replacement after total gastrectomy is still missing. Diagnoses are made too late in a population of patients, resulting in irreversible neurological sequale, and we suggest that Pernicious anemia seems not to be very rare in Korea.

포스터 전시 발표 : 혈액종양 ; 국소 진행성 두경부암의 Taxotere와 Capecitabine의 선행항암화학요법의 치료 효과 (예보)

곽승근,박남숙,박수진,박상은,신현영,김성은,윤환중,조덕연,김삼용,박석원,이오영,송창준,조문준,김진만,김은석,정일혁 대한내과학회 2002 대한내과학회 추계학술대회 Vol.63 No.-

Thrombotic Thrombocytopenic Purpura(TTP)에 병발된 Reversible Posterior Leukoencephalopathy syndrome(RPLS)

곽승근,양종오,장윤경,송창준,이강욱,신영태 대한내과학회 2001 대한내과학회 추계학술대회 Vol.61 No.-

미만성 대형 B-세포 림프종에서의 예후인자에 관한 연구

김삼용,곽승근,박상은,윤환중,조덕연,김진만 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

미만성 대형 B-세포 림프종은 가장 흔한 악성 림프종의 한 종류로서 우리나라에서는 전체 비호지킨 림프종의 50%를 차지한다. 비호지킨 림프종에서 병기는 호지킨병과는 달리 예후 인자로서의 유용성이 적다. 따라서 병기만을 예후 인자로서 평가하는 한계를 극복하기 위해 국제예후지표(International Prognostic Index)가 도입되었다. 특정 환자에서 IPI 점수와 함께 그 환자의 림프종의 생물학적 특성을 분석한다면 예후 예측에서 정확도가 높아질 것이다. 본 연구에서는 미만성 대형 B-세포 림프종에서 국제예후지표의 유용성을 확인하고자 하였으며, 각종 생물학적 지표의 면역화학염색을 통하여 이들을 배세포 중심 아형(germinal center subgroup : 이하 GC양 아형으로 약함)과 활성화 B-세포 아형(post-germinal center subgroup; 이후 pGC양 아형으로 약함)으로 분류하고 이들의 예후 예측에 대한 적절성을 평가하였다. 결과는 다음과 같다. 1. 연령분포는 37세에서 69세로 중앙치는 56세이었으며, 남자는 17예(65.4%), 여자가 9예(34.6%)였다. 병기는 Ⅰ, Ⅱ, Ⅲ, Ⅳ기가 각각 2예(7.7%), 11예 (42.3%), 5예(19.2%), 8예(30.8%)였다. 'B'증상은 5예(19.2%)에서 양성이었다. 진단 당시 혈청 LDH치가 상승한 경우가 11예(42.3%)였고, 거대종양(직경이 10㎝이상)을 갖는 경우가 5예(19.2%)이었다. ECOG 수행등급은 0이 2예(7.7%), 1이 18예(69.2%), 2가 5예(19.2%), 3이 1예(3.8%)이었다. 2. 면역조직화학염색 상 bcl-2의 양성은 17예(65.4%), bcl-6의 양성이 20예(76.9%)이었다. CD10이 양성인 경우가 5예(19.2%)이었다. IRF-4가 양성인 경우는 8예(30.8%)였다. 26명의 환자에서 bcl-6, CD10과 IRF-4를 이용하여 GC양 아형과 pGC양 아형으로 분류 하였는데, GC양 아형은 14예(53.8%)이었고, pGC양 아형은 7예(26.9%), 분류가 되지 않는 경우가 5예(19.3%)이었다. 3. 평균 48개월 동안 추적한 결과 중앙생존기간은 44개월이었고 생존기간은 1~100+개월에 분포하였다. Kaplan-Meier법에 의한 5년 누적 생존률은 32%이었다. 4. 병기, 'B' 증상, 혈청 LDH 농도, ECOG 수행등급, 거대종양유무가 통계학적으로 의미있는 임상적 예후 인자였다. 5. 면연조직화학염색에서는 bcl-2만이 통계학적으로 유의한 예후인자였다. 6. GC양 아형은 pGC양 아형에 비해 생존기간은 좋았으나, 통계학적 유의성은 없었다. 7. 다변량 분석결과 bcl-2 발현과 혈청 LDH치만이 예후에 영향을 미쳤다. Clinical Significanceof Expression of Biomarkers in Patients with Diffuse Large B-cell Lymphoma Diffuse large B-cell lymphoma(DLBL) is the most common type of lymphoma in Korea, representing about 50% of non-Hodgkin's Lymphomas. Although DLBL is usually considered as a specific category, the diversity in clinical presentation, morphology, genetic and molecular alterations strongly suggest that these tumors represent a heterogeneous group of neoplasia rather than a single clinicopathological entity. Clinical prognostic systems, including the International Prognostic Index (IPI), although useful to assess overall prognosis, embraces patients with heterogeneous prognoses. It is likely that the prognostic assessment of patients with DLBL might be improved by using biological features. During the last decade, most studies dealing with the heterogeneity of DLBL have focused on individual protein expression and molecular alterations. The expression of individual antigens related to different stages of B-cell differentiation, including CD10, bcl-6, and IRF-4, may help to define groups of tumors with different clinical and pathological characteristics. To determine the clinical significance and prognostic value of individual biomarker expression and the biomarker expression patterns according to germinal center subgroup or post-germinal center subgroup of DLBL as defined by a relatively small number of single antigens, we studied 26 patients with de novo DLBL, whose archival pathology specimen were available for immunohistochemistry studies, atChungnam National University Hospital from September 1992 to December 2000. Archival specimens from each patient were immunostained with respective antibodies for CD10, bcl-6, IRF-4, bcl-2 antigens. Two immunophenotyping profiles were distinguished according to the pattern of differentiation; germinal center(GC;CD10/Bcl-6+/IRF-4-) subgroup or postgerminal center (pGC ; CD10/bcl-6/IRF4+) subgroup. The results are as follows; 1) Baseline characteristics of patients were ; median age of patients was 56(range ; 37-69). 17 patients(65.4%) were male. 5 patients(l9.2%) had 'B' symptoms. Stages were as follows ; stage Ⅰ2 patients(7.7%), stage Ⅱ 11 patients(42.3%), stage Ⅲ 5 patients(l9.2%), stage Ⅳ 8 patients(30.8%). 11 patients (42.3%) had elevated LDH levels. 25 patients(96.2%) had ECOG performance grade 0-Ⅱ and 1 patient had grade Ⅲ. 5 patients(l9.2%) bad bulky disease. 2) The results of immunohistochemical study were as follows ; positive bcl-2 staining in 17 patients(65.4%), positive bcl-6 in 20 patients(76.1%), positive CD10 in 5 patients(l9.2%), positive IRF-4 staining in 8 patients (30.8%). 3) After a median follow up duration of 48 months, the median survival duration was 44 months with a range of survival of 1-100+ months. 5-year overall survival rate was 32% by Kaplan-Meier method. 4) The clinical factors affecting survival were elevated serum LDH level, B symptoms, bulky disease, stage at diagnosis and ECOG performance status 5) Among the biomarkers, only bcl-2 expression affected survival of DLBL patients 6) The germinal center like subgroup had superior survival than post-germinal center like subgroup but had no statistical significance. 7) Multivariate analysis showed that bcl-2 and serum LDH level had siginificance on survival Conclusion In addition to the known clinical prognostic factors, immunohistochemically defined characteristics such as bcl-2 expressionin DLBL is important and subgroups(germinal center or post-germinal center subgroup) of DLBL may have importance in predicting prognosis of DLBL patients

포스타 전시 발표 : 혈액종양 ; Oxymetholone치료가 재생불량성빈혈 환자의 생존에 미치는 영향

신현영,곽승근,김성은,이정찬,이정호,윤환중,조덕연,김삼용 대한내과학회 2001 대한내과학회 추계학술대회 Vol.61 No.-

중독한 추체로 증상을 보인 cyclosporine에 의한 뇌증 1예

강정현,곽승근,신현영,김성은,이정호,이정찬,곽상혁,윤환중,조덕연,김삼용,김제,송창준 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.1

The use of cyclosporine(CsA), a potent immunosuppressive agent, is associated with numerous side effects. Neurotoxicity was earlier less well known, but with growing experience central nervous system side effects are now reported up to 40% of patients. Among various CsA-induced neurotoxicities, tremor is most common and posterior leukoencephalopathy is well characterized. An encephalopathy presenting with pyramidal weakness, however, seems to be rare and poorly documented. We report here a case of encephalopathy presenting with multiple generalized seizures followed by fluctuating quadriparesis developed a few days after starting CsA and resolved spontaneously after withdrawal of the drug . A 48-year-old woman with aplastic anemia was placed upon immmunosuppressive treatment consisting of antithymocyte globulin(ATG), CsA, and methylprednisolone. Two days after starting the therapy, she developed a generalized seizure. The next day she developed 2 more episodes of seizure and the therapy was stopped. Computed tomogram of the brain was normal. Six days after starting therapy, she developed mild motor weakness and paresthesia of both lower extremities, which progressed to a definite quariparesis confining her to a bed in 3 days. Magnetic resonance imaging(MRI) of the brain revealed asymmetric, bilateral high-signal abnormalites in the subcortical white matter of fronto-temporal areas. After reaching to a maximum with some fluactuation(14 days after starting the therapy) the motor weakness started to be resolved. She was discharged with a almost complete resolution of the weakness 45 days after starting the therapy. Five months later she did well and brain MRI was negative.

재생불량성빈혈 치료에서 Oxymetholone의 역할

신현영,김성은,곽승근,박상은,박수진,윤환중,조덕연,김삼용,권계철 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.1

Response rate to androgen therapy in aplastic anemia has been reported at 20-50%, and patient survival of the treatment group was not different from control group in several randomized trials. We wanted to confirm our hypothesis that the clinical behavior of aplastic anemia in Korea is different from western countries by documenting better response rate and longer survival of aplastic anemia patients who were treated with androgen only. We analyzed retrospectively the data of 51 patients with aplastic anemia who were diagnosed and treated with 100㎎/day of oxymetholone during the period of January 1990 - December 2000. The results are as follows. The sex ratio was 23:28 or 1.21. There were 26 moderate aplastic anemia versus 25 severe aplastic anemia patients. The median age of patients was 42 (18-82) years. 43 (84.3%) patients received oxymetholone as the first-line treatment (Group l), whereas 8 (15.7%) patients received oxymetholone after failure of immunosuppressive therapy (Group 2) Among 43 patients in Group 1, 7 (16%) patients obtained complete response and 16 (37%) patients achieved partial response with an overall response rate of 53%, and among 8 patients in Group 2,1 (13%) patients obtained complete response and 5 (63%) patients partial response with an overall response rate of 75%. There was no significant difference in survival rates between Group 1 and Group 2 (p=0.259). The overall response rate was 57%. Among 29 patients in response group, 21 (72%) patients survived and among 22 patients in Non-response group, 8 (36%) patients survived. There was a significant difference in survival rates between Response group and Non-response group (p=0.020). The overall survival rate was 57%. Kaplan-Meier analysis revealed a longer survival in responders (p=0.0029). The oxymetholone treatment in patients with aplastic anemia increases survival rates and prolongs the survival duration.

조혈세포에 대한 조혈성장인자의 단기간 처리가 CXCR4 발현 및 Stromal Cell-Derived Factor-1 (SDF-1) 매개 경내피세포 이동에 미치는 영향

조덕연,황진희,곽승근,신현영,김성은,윤환중,성주명,김삼용 大韓血液學會 2001 大韓血液學會誌 Vol.36 No.4

동일한 국제예후지표(International Prognostic Index)를 나타내는 미만성 대형 B-세포 림프종에서 Bcl-2와 p16의 임상적 중요성

박상은,박수진,곽승근,박남숙,천재민,윤환중,조덕연,김삼용,김진만 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

In Korea, malignant lymphoma is a common cancer, comprising about 2.7% of all malignant neoplasm. Diffuse large B cell lymphoma is the most common lymphoma, representing about 50% of all Non-Hodgkin's lymphoma. Diffuse large B-cell lymphoma is usually considered as heterogeneous group of neoplasms rather than a single clinicopathological entity. Clinical prognostic systems, including the International Prognostic Index (IPI), although useful to assess overall prognosis, embrace patients with heterogeneous prognoses. But International Prognostic Index scoring system is not sufficiently predict the prognosis. It is likely that the prognostic assessment of patients with diffuse large B-cell lymphomamight be improved by using biological features. Bcl-2 protein and p16 protein expression is recognized as useful biologic markers predicting the prognosis of patients with diffuse large B-cell lymphoma. To determine the clinical significance and prognostic value of bcl-2 and p16 proteins expression patterns, we studied 18 patients with de novo DLBL, whose archival pathology specimen were available for immunohistochemistry studies, atChungnam National University Hospital from September 1992 to December 2000. Archival specimens from each patient were immunostained with respective antibodies for bcl-2, p16. The results are as follows; 1) The median age was 54(rage : 37-69). There were 12 male patients(66.7%) and 6 female patients(33.3%) The 'B' symptom was abscentin all patients. The stages were as follows : Ⅰ, 2 patient(11.1%), Ⅱ, 10 patient(55.6%), Ⅲ, 4patient(22.2%) and Ⅳ, 2patient(11.1%). 3 patients(16.8%) had the elevated LDH level, 14 patients(77.8%) had the normal LDH level and 1 patients(5.6%) was not identified the LDH level. 2 patients(11.1%) had the bulky disease and 16 patients(88.7%) had no bulky diease. The distribution of ECOG status were O, 2 patients(11.1%c), 1, 14patients(77.8%) and 2, 2patients(11.1%). 2) Theimmunohistochemistry results are as follows bcl-2:+,10 patients(55.6%), bcl-2:-, 8patinets(44.4%), p16:+,3 patients(16.7%), p16:-, 15patients(83.3%) 3) After a median follow UP durations of 67 months, the median survival time was 57 months with a rage of 7-100+ months. 5-years overall survival rates was 44% by Kaplan-Meier method. 4) Reduced overall survival was demonstrated in the patients who expressed bcl-2 protein(P=0.0174). 5-year overall survivial rate was 12%(bcl-2 expression) versus 88%(no bcl-2 expression) 5) Among diffuse large B-cell lymphoma patients with IPI score 0-1, reduced overall survival was demonstrated with bcl-2 expression(P=0.023). 5-year overall survival rate was 18%(bcl-2 expression group) versus 100%(no bcl-2 expressiongroup) 6) Median survival durtation of diffuse large B-cell lymphoma patients negative for p16 expression was 57 months whereas p16 postive patients' median survival duration was not reached(P=0.4478). In diffuse large B-cell lymphoma patients with identical IPI scores, bcl-2 expression had additional prognostic value.

후두암의 치료 성적

김성은,신현영,곽승근,박상은,박수진,윤환중,조덕연,김삼용,김병국 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.1

Laryngeal cancer-the most common malignant tumor within head and neck-is known for its better prognosis when we compare with the other malignancies. In this paper, We analyzed retrospectively results of operation, radiotherapy and chemotherapy of laryngeal cancer to find out the response rate, survival rate and prognostic factor. 75 consequent laryngeal cancer patients who have been treated at CNUH during the period of 1995 to 2000 were studied. The patients are consisted of 72 males and 3 females. The primary site were; glottis in 45 patients, supraglottis in 29 patients, and subglottis in 1 patient. 96% had squamous cell carcinoma and 98% of evaluable patients had history of smoking. Glottic cancer was detected earlier and showed much better prognosis than supraglottic cancer (p <0.001). 45 patients received radiotherapy while 17 patients underwent surgery and post -operative radiotherapy. Complete remission rate after radiotherapy was 85.7% in glottic cancer patient. Three year overall survival rate was 85.4 % in total. Significant prognostic factor for 3-year overall survival and 3-year disease free survival on univariate analysis were stage, T stage, and primary site. 3-year overall survival rate was higher in patients with negative lymph node involvement. Progression or recurrence usually occurred within 12 months in responsive group. Chemotherapy was the primary treatment modality in 9 patients and 6 patients recieved additive radiotherapy. Among 9 patients, 2 patients obtained complete remission and 1 patient achieved partial response after subsequent radiotherapy. Advanced cancer patients after surgery with radiotherapy achieved high survival rate, but lost larynx function. We need to develop better strategies to increase both voice preservation and survival rate in patients with advanced laryngeal cancer.