고위험군의 원발성 전신성 유전분증 1례 보고 및 조혈모세포이식에 대한 문헌고찰

심준,박수정,엄현석,김기영,박은정,강인중,조병식,이안희,한치화 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

저자 등은 클론성 형질세포질환과 동반된 젊은 연령의 원발성 전신성 유전분증 환자를 진단하였기에 다발성 골수종과의 감별 진단, 치료 , 예후 및 고용량 항암화학요법과 조혈모세포이식에 관하여 문헌고찰과 함께 보고하는 바이다. Primary systemic amyloidosis (AL) is a rapidly fatal disorder related to plasma cell dyscrasia. Conventional dose of melphalan, which prolongs the duration of survival by about 10 months, does not improve the functions of impaired organs in most cases. The high dose chemotherapy followed by autologous hematopoietic stem cell rescue for AL, in spite of its high treatment-related mortality, is a new approach to achieve high response rate and better survival. We experienced a 35-year old man with AL(involving heart, liver, stomach, kidneys, peripheral nerve, and rectum) who did not respond to the standard schedule of melphalan plus prednisone and had rapidly fatal course with organ failure. Hence, we evaluate its availability by reviewing the recent reports of high dose chemotherapy in AL.

암 환자의 우울과 통증 : 일 예비적 연구

양문정,전양환,한상익,한치화,엄현석 대한신경정신의학회 2000 신경정신의학 Vol.39 No.6

연구목적 : 암 환자에서 우울과 통증의 정도, 우울과 통증에 영향을 줄 수 있는 요인들을 조사하고, 우울과 통증사이에 어떤 연관이 있는지 알아보고자 하였다. 방 법 : 종양내과에 입원한 암 환자 25명(남자 : 10명, 여자 :15명)을 대상으로 하여 내과 병록지 거모, 환자 및 가족과의 면담을 시행하였다. 정신과적 진단은 DSM-IV진단 기준에 의하였으며, 우울의 정도는 Hamilton Rating Scale for Depression(HRSD)로 평가하였고 통증의 유무를 평가한 뒤, 통증이 있는 경우 Brief Pain Inventory(BPI)를 시행하여 통증의 강도(최대, 최소,평균,현재), 통증에 의한 기능 방해 정도, 진통제에 의한 호전정도를 점수로 평가하였다. 결 과 : 전체 환자중 주요 우울증이 32%(8명), 경도 우울증이 16%(4명), 적응장애가 16%(4명)이었다. HRSD점수는 통증의 최대강도, 평균강도, 현재강도, 통증에 의한 기능방해정도와 유의한 상관관계가 있었으나, 통증의 최소강도, 진통제에 의한 호전 정도와는 유의한 상관관계가 없었으며, 이환 기간과 HRSD점수 및 통증 점수 사이에도 유의한 상관관계가 없었다. 성별, 종교, 암의전이여부,병황의 인식 여부에 따라 HRSD점수와 통증 점수에 차이가 없었으나, 현재 미혼 또는 사별 상태에 있는 환자들에서 결혼하여 배우자가 있는 환자들보다 HRSD점수와 통증의 최소강도, 평균강도가 유의하게 높았다. 결 론 : 암환자에게서는 우울증과 통증이 있는 경우가 많았다. 우울증과 통증간에 밀접한 상관관계가 있음을 알수 있었다. 본 연구의 결과는 암 환자에서 우울증과 통증에 대한 보다 적극적인 평가와 개입이 이루어져야 함을 시사하는 것이다. Objective : This study was designed to evaluate how much depression and pain symptoms could be shown, what kink of factors affect them, and whether the correlation between them could be or not in patients with cancer. Methods : The subjects were composed of 25 patients with cancer who admitted a the department of oncology(male:10, female :15). We reviewed the medical record and interviewed patients and their family. A psychiatric diagnosis was made according to the criteria of the DSM-IV, and depressive symptoms were evaluated by Hamilton Rating Scale for Depression(HRSD). The intensity of pain(maximal, minimal, mean, present), disability due to pain, te effects of analgesics were measured by Brief Pain Inventory(BPI). Results : 32% of patients had major depressive disorders, 16% of patients had depressive disorders, NOS and 16% of the patients had adjustment disorders. The score of HRSD was significantly correlated wit the maximal intensity, mean intensity and present intensity of pain and disability due to pain, but not with minimal intensity and the effects of analgesics. Depression and pain were not correlated with duration of illness. Scores of depression and pain did not differ in sex, religion, metastasis, and the knowledge of illness. The widowed or unmarried patients showed significantly higher scores than patients living with the spouse in HRSD, minimal intensity and mean intensity of pain. Conclusion : In patients with cancer, depression and pain were highly prevalant. The relationship between depression and pain was shown in patients with cancer. These results suggest that more active evaluation and intervention of depression and pain should be carried out in patients with cancer.

Absence of oncogenic AKT1 E17K mutation in prostate, esophageal, laryngeal and urothelial carcinomas, hepatoblastomas, gastrointestinal stromal tumors and malignant meningiomas.

Eom, Hyeon Seok,Kim, Min Sung,Hur, Soo Young,Yoo, Nam Jin,Lee, Sug Hyung Acta Oncologica 2009 Acta Oncologica Vol.48 No.7

Bortezomib, thalidomide, dexamethasone induction therapy followed by melphalan, prednisolone, thalidomide consolidation therapy as a first line of treatment for patients with multiple myeloma who are non-transplant candidates: results of the Korean Multi

Eom, Hyeon-Seok,Kim, Yeo-Kyeoung,Chung, Joo-Seop,Kim, Kihyun,Kim, Hyo Jung,Kim, Ho Young,Jin, Jong-Youl,Do, Young-Rok,Oh, Suk-Joong,Suh, Cheolwon,Seong, Chu-Myong,Kim, Chul Soo,Lee, Dong Soon,Lee, Jae Springer-Verlag 2010 Annals of hematology Vol.89 No.5

정상 위 분문부 점막에서 발견된 이소성 골 형성

엄석현 ( Seok Hyeon Eom ),박창환 ( Chang Hwan Park ),정덕원 ( Duk Won Chung ),이상혁 ( Sang Hyeok Lee ),서지영 ( Ji Young Seo ),김영성 ( Yeong Sung Kim ),곽동협 ( Dong Hyup Kwak ),김정희 ( Jung Hee Kim ) 영남대학교 의과대학 2016 Yeungnam University Journal of Medicine Vol.33 No.2

Heterotopic bone formation in the gastrointestinal tract is a rare phenomenon. Most reported cases were associated with benign and malignant neoplasms, except for a case in which heterotopic bone formation was found in a patient with Barrett`s esophagus. The exact pathogenesis of the disease has not yet been established. However, most heterotopic bones found in the gastrointestinal tract were associated with mucinproducing tumors of the appendix, colon, and rectum. Inflammation may also play a role in osseous metaplasia in a case with bone formation at the base of an ulcer in Barrett`s esophagus. Here, we report on a patient with heterotopic bone formation in normal gastric cardiac mucosa. A 50-year-old female visited our hospital for a routine health examination. She had no gastrointestinal symptoms, and her physical examination, blood test, X-ray, urine, and stool examination results were normal. A 0.3 cm sized polypoid lesion located just below the squamocolumnar junction was observed on upper gastrointestinal endoscopy. A piece of biopsy was taken. Histologically, a lamella bone trabecula and chronic inflammatory cells were observed in the gastric cardiac mucosa. The follow-up endoscopy performed one month later showed no residual lesion.

Concurrent chemoradiotherapy followed by l-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study

Kim, Seok Jin,Yang, Deok-Hwan,Kim, Jin Seok,Kwak, Jae-Yong,Eom, Hyeon-Seok,Hong, Dae Sik,Won, Jong Ho,Lee, Jae Hoon,Yoon, Dok Hyun,Cho, Jaeho,Nam, Taek-Keun,Lee, Sang-wook,Ahn, Yong Chan,Suh, Cheolwon Springer-Verlag 2014 Annals of hematology Vol.93 No.11

PML/RAR-α 유전자 동형의 임상적 의의가 있는가?

엄현석 ( Hyeon Seok Eom ) 대한내과학회 2008 대한내과학회지 Vol.75 No.4

Acute promyelocytic leukemia (APL) is characterized by a specific t (15;17) translocation which produce a PML/RAR-α fusion messenger RNA and by effectiveness of all-trans retinoic acid (ATRA) differentiation therapy. Breakpoints within PML intron 3 (bcr 3) produce a short PML/RAR-α isoform (S-isoform), whereas breakpoints within PML intron 6 (bcr 1) result in a longer form (L-isoform). Additionally, breakpoints within PML exon 6 (bcr 2) make a variable length transcript (V-isoform) in a small number of patients. The influence of breakpoint site on patient outcome remains controversial. Previous reports showed that patients with S-isoform have an increased incidence of clinical relapse and shorter survival compared to those with L-isoform. Others reported no difference in DFS between these patients groups. In this issue, Lee et al. reported that there were 58 L-isoform (62.1%), 32 S-isoform (34.0%), 4 V-isoform (4.3%) and, no significant prognostic factor for EFS from induction therapy using anthracycline plus ATRA among 94 patients with APL. They concluded pretreatment clinical characteristics and treatment outcomes were not significantly different according to PML/RAR-α isoform types in this induction group. Recently, it was reported that FLT3/ITD mutation was frequently associated with S-isoform and with the M3v form of leukemia and CNS relapse in APL was mostly related to S-isoform. With previous studies including this article, outcomes of different types of PML/RAR-α isoforms are not conclusive. Future researches need to be focused not only on clinical outcomes of different types of PML/RAR-α isoforms, but also clinical relevance of PML/RARA-α mRNA isoforms with other prognostic factors and particular clinical characteristics. (Korean J Med 75:409-411, 2008)

Multicenter analysis of treatment outcomes in adult patients with lymphoblastic lymphoma who received hyper-CVAD induction followed by hematopoietic stem cell transplantation.

Jeong, Seong Hyun,Moon, Joon Ho,Kim, Jin Seok,Yang, Deok-Hwan,Park, Yong,Cho, Seok Goo,Kwak, Jae-Yong,Eom, Hyeon Seok,Won, Jong Ho,Hong, Jun Shik,Oh, Sung Yong,Lee, Ho Sup,Kim, Seok Jin Springer International 2015 Annals of hematology Vol.94 No.4

<P>The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n?=?16) and allogeneic SCT (n?=?8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.</P>

Regulation of Acetylation of Histone Deacetylase 2 by p300/CBP-Associated Factor/Histone Deacetylase 5 in the Development of Cardiac Hypertrophy

Eom, Gwang Hyeon,Nam, Yoon Seok,Oh, Jae Gyun,Choe, Nakwon,Min, Hyun-Ki,Yoo, Eun-Kyung,Kang, Gaeun,Nguyen, Vu Hong,Min, Jung-Joon,Kim, Jong-Keun,Lee, In-Kyu,Bassel-Duby, Rhonda,Olson, Eric N.,Park, Woo Grune & Stratton 2014 Circulation research Vol.114 No.7

<P><B><U>Rationale:</U></B></P><P>Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear.</P><P><B><U>Objective:</U></B></P><P>Recently, we suggested that casein kinase 2α1–dependent phosphorylation of HDAC2 leads to enzymatic activation, which in turn induces cardiac hypertrophy. Here we report an alternative post-translational activation mechanism of HDAC2 that involves acetylation of HDAC2 mediated by p300/CBP-associated factor/HDAC5.</P><P><B><U>Methods and Results:</U></B></P><P>Hdac2 was acetylated in response to hypertrophic stresses in both cardiomyocytes and a mouse model. Acetylation was reduced by a histone acetyltransferase inhibitor but was increased by a nonspecific HDAC inhibitor. The enzymatic activity of Hdac2 was positively correlated with its acetylation status. p300/CBP-associated factor bound to Hdac2 and induced acetylation. The HDAC2 K75 residue was responsible for hypertrophic stress–induced acetylation. The acetylation-resistant Hdac2 K75R showed a significant decrease in phosphorylation on S394, which led to the loss of intrinsic activity. Hdac5, one of class IIa HDACs, directly deacetylated Hdac2. Acetylation of Hdac2 was increased in Hdac5-null mice. When an acetylation-mimicking mutant of Hdac2 was infected into cardiomyocytes, the antihypertrophic effect of either nuclear tethering of Hdac5 with leptomycin B or Hdac5 overexpression was reduced.</P><P><B><U>Conclusions:</U></B></P><P>Taken together, our results suggest a novel mechanism by which the balance of HDAC2 acetylation is regulated by p300/CBP-associated factor and HDAC5 in the development of cardiac hypertrophy.</P>

만성 골수성 백혈병의 가속기에서의 동종 골수이식

엄현석,이종욱,김동욱,박수정,서정곤,민창기,김희제,한치화,민우성,김춘추,김동집 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.2

목적: CML 환자들을 대상으로 실시한 동종 골수이식의 후향적 분석을 통해서 만성기, 가속기, 급성기에 따른 생존 기간의 차이와 가속기에 시행한 이식에서 장기 생존과 관련된 요인들을 분석하고 특히 이중에서 진단 후 이식까지의 기간에 따른 생존 기간의 차이와 전처지 방법에 따른 생존 기간의 차이를 알아보고자 하였다. 대상: 1986년 9월부터 1997년 12월까지 성모병원 가톨릭 조혈모세포이식센터에 입원하여 조직적합성 항원(HLA)이 일치하는 형제로부터 동종 골수 이식을 시행 받은 94명의 성인 환자를 대상으로 하였다. 의무 기록을 후향적으로 분석하여 만성기, 가속기, 급성기에 골수 이식을 시행 받은 환자의 생존 기간을 분석하고, 24예의 가속기 환자에서의 진단 후 이식까지의 기간과 전처치 방법에 따라 생존에 차이가 있는가를 분석하였다. 관찰 기간은 1-144개월(중앙값 21개월)이었고 최소 추적 관찰 기간은 9개월이었다. 결과: 전체 환자 94예 중 만성기에 이식을 받은 환자의 5년 무병 생존율은 48%이고, 가속기에 받은 환자는 36%, 그리고 급성기는 14%였으며 통계적으로 유의한 차이를 보였다(p=0.0015). 만성기에 이식을 받은 환자의 5년 전체 생존율은 62%이고, 가속기에 받은 환자는 53%, 그리고 급성기는 14%였다(p=0.0119). 가속기 환자 24예 중 진단 후 이식까지의 기간이 1년 미만인 경우(n=9)의 5년 생존율은 65%, 1년 이상인 경우(n=15)는 48%였으며, 진단부터 이식까지의 기간이 짧을수록 생존 기간이 증가되는 경향을 보였다(p=0.0734). 전처치 방법에 따른 생존 기간의 차이는 TBI를 포함한 군(n=18)과 Bu+Cy 군(n=6)에서 차이가 없었다(p=0.6829). 가속기에서 이식 받은 환자 24예 중 재발은 10예에서 나타났으며 이 중 3명은 공여자 림프구 투여 혹은 인터폐론 치료로 재관해가 유도되어 생존하고 있다. 급성 및 만성 GVHD가 있었던 경우재발률은 31%(5/16)인 반면, GVHD가 나타나지 않았던 경우는 62%(5/8)의 재발률을 보였다. 3예에서 이식과 관련된 합병증으로 사망하였으며 각각 뇌막염, 급성 GVHD와 동반된 간질성 폐렴, 그리고 생착 부전이 1예씩이었다. 결론: 가속기에서 골수이식을 시행하는 경우 장기생존율 53%의 성적은 고무적인 것으로 적극적으로 이식을 권장할만 하다. 또한 가속기에서 이식을 할 경우 가급적 진단부터 1년 이내의 조기에 이식을 실시하는 것이 생존율을 증가시킬 것으로 사료되며,이식 후 재발의 예방을 위한 면역 치료에 대한 지침을 개발 하는 것이 중요하리라 생각된다. Background: Allogeneic bone marrow transplantation (BMT) remains the gold standard therapy for chronic myelogenous leukemia (CML). The best results are obtained when patients receive the transplant during the chronic phase (CP) of the disease. However, some patients may progress to accelerated phase (AP) or blastic phase (BP) before transplantation. Methods: Between 1986 and 1997 we performed allogeneic BMT for 94 patients with CML from HLA-matched sibling donors. We reviewed records of 24 patients receiving transplants during the AP of CML. The median age of patients was 29(17~38), and median interval from diagnosis to transplants was 14.5 months(3~46). TBI-containing regimen(n=18) and BuCy(n=6) were used as conditioning regimen. GVHD prophylaxis consisted of CsA+MTX(n=20) and CsA(n=4). Median mononuclear cell dose infused was 1.2×10^(8)/kg(1.04~2). Results: 5-year probabilities of overall survival and disease-free survival were 53% and 36%, respectively. Early transplanted patients within 1 year after diagnosis had a trend toward to better survival, but there was no statistical significance(65% vs 48%; p=0.07). Among 10 relapsed patients, 3 are alive in remission after donor lymphocyte infusion and/or interferon therapy. Three patients died of transplantation-related mortality including meningitis(n=1), interstitial pneumonia with acute GVHD(n=1), and graft failure(n=1). Conclusion: Because the results of allogeneic BMT for patients in AP are promising, we suggest that BMT should be actively recommended even in AP as early as possible for better outcome. The high probability of relapse in AP patients will be required the intensified conditioning regimen or posttransplant immunotherapy. Relapse can be treated with interferon or with infusion of donor lymphocytes. The adoptive immunotherapy will improve the survival for patients receiving transplants in AP CML.