소세포폐암의 임상경과 및 예후인자

장대영(Dae Young Zang),이정신(Jung Shin Lee),김태원(Tae Won Kim),정병학(Byung Hak Jung),윤환중(Hwan Jung Yun),최종수(Jong Soo Choi),박진희(Jin Hee Park),이동숙(Dong Sook Lee),이제환(Je Hwan Lee),김성배(Sung Bae Kim),김상위(Sang We Ki 대한내과학회 1998 대한내과학회지 Vol.54 No.1

N/A Background: Although small cell lung cancer is a chemosensitive disease, it grows rapidly and relapses frequently. Even with optimum treatment, only small portion of patients have experienced long-term survival. The objective of this study was to describe the clinical characteristics and therapeutic features, and to analyze the prognosis in small cell lung cancer. Methods: We analyzed retrospectively 151 evaluable patients with histologically confirmed small cell lung cancer from August 1989 to June 1995 at our institution. Of 151 patients, 3 had surgery and chemotherapy, 59 had chemotherapy and chest irradiation, and 89 had chemotherapy only. Results: Most patients(82.1%) were men, and the median age was 62 years. Of all patients, 49% had performance status of 0.1 and 59.6% had limited disease. The overall response rate was 67.8% : complete response 23.8%, partial response 44.4%. Complete responses were documented in all of three patients who had surgery and chemotherapy, 49.2% of those who had chemotherapy and radiotherapy, and 4.5% of those who had chemotherapy only. The median follow-up duration was 309 days. The median progression-free survival and overall survival were 256 days and 354 days, respectively: patients who had surgery and chemotherapy were 1631 days and 1631 days, those who had chemotherapy and radiotherapy were 344 days and 450 days, and those who had chemotherapy only were 186 days and 278 days, respectively; complete responders were 580 days and 710 days, partial responders were 231 days and 364 days, non-responders were 132 days and 151 days, respectively. Of 151 patients, 11.3% survived more than two years(long-term survival). Most long-term survivors had limited disease(82.4%) and good performance(76.5%). Long-term survival ocurred in two patients of those who had surgery and chemotherapy, 16.9% of those who had chemotherapy and radiotherapy, and 5.6% of those who had chemotherapy only. Most long-term survivors(70.6%) had complete response. Twenty of 36 complete responders and 8 of 17 long-term survivors had disease relapses or progressions. Patients with limited disease, those with good performance, and those with normal alkaline phosphatase had a significantly higher complete response rate and longer progression-free survival and overall survival than their counterparts. Of pretreatment characteristics, stage and performance status were correlated complete response and survival, independently. Complete response outcome was significant independent variable for survival. Conclusion: The disappointing results in this disease support the need for both new treatment strategies to improve complete response rate and to decrease relapse rate and large-scaled prospective studies to know natural history of long-term survivors.

증례 : 혈액종양 ; 류마티스관절염이 동반된 고전형 카포시육종의 에토포사이드 치료 1예

최난영 ( Nan Young Choi ),박승아 ( Seung Ah Park ),한보람 ( Bo Ram Han ),김호영 ( Ho Young Kim ),민수기 ( Soo Kee Min ),김효정 ( Hyo Jung Kim ),장대영 ( Dae Young Zang ) 대한내과학회 2014 대한내과학회지 Vol.86 No.2

본 저자들은 류마티스관절염을 처음 진단받고 면역저하의 증거가 없으며 HHV-8 음성이며 전신상태가 좋지 않은 고령의 환자에서 전신 피부에 발생한 4병기 고전형 카포시 육종을 진단하였고 지속적인 저용량 경구 에토포사이드 단독요법으로 좋은 임상경과를 얻은 증례가 있어 보고하는 바이다. Kaposi`s sarcoma typically occurs in immunocompromised patients, especially those with acquired immunodeficiency syndrome. Human herpesvirus 8 (HHV-8) and human immunodeficiency virus (HIV) may play important roles in the development of Kaposi`s sarcoma. We report the case of a 75-year-old male who presented with progressive multiple purplish papules and nodules on the skin for 3 months. Social and past medical histories seemed incompatible with an immunesuppressed condition and tests for HIV antibodies and HHV-8 were negative. He was newly diagnosed with rheumatoid arthritis, according to the 2010 ACR-EULAR criteria. Typical findings of Kaposi`s sarcoma were confirmed by biopsy. After treatment with metronomic oral etoposide 25 mg once daily for 9 months, the skin lesions had almost resolved with no serious complication. Thus, we report a rare case of Kaposi`s sarcoma developing in a patient with newly diagnosed rheumatoid arthritis who showed a good response to oral etoposide. (Korean J Med 2014;86:247-252)

증례 : 유방으로 전이된 비소세포 폐암 1예

김기성 ( Ki Seong Kim ),장대영 ( Dae Young Zang ),김효정 ( Hyo Jung Kim ),안진석 ( Jin Seok Ahn ),유지연 ( Ji Youn Yoo ),홍기우 ( Ki Woo Hong ),박혜림 ( Hye Rim Park ) 대한내과학회 2005 대한내과학회지 Vol.69 No.-

저자들은 비소세포 폐암을 진단받은 후 우폐상엽 절제술 및 림프절 곽청술을 시행 받고 추적관찰 중에 있는 환자에서 만져지는 유방 종괴가 비소세포 폐암의 유방전이로 확진되어 고식적 항암치료 중인 예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Development of metastasis to the breast from lung cancer is extremely rare and the prognosis for such patients is poor. A 50-year old woman was diagnosed as non-small cell lung cancer (adenocarcinoma,well differentiated) of the right upper lobe. She underwent right upper lobectomy with radical lymph nodes dissection. After 6 months, she had a palpable mass in the upper inner quadrant of the right breast, the breast tumor was proved to be of pulmonary origin. A correct diagnosis of metastasis to the breast is of considerable importance since the treatment of primary and secondary malignancies of the breast is markedly different, with considerably different outcomes. We report a case of metastatic breast cancer from non-small cell lung cancer. (Korean J Med 69:S835-S839, 2005)

위암의 보조항암화학요법

류민희 ( Min Hee Ryu ),장대영 ( Dae Young Zang ) 대한내과학회 2012 대한내과학회지 Vol.83 No.3

Gastric cancer remains the second most common malignancy worldwide. Surgical resection with D2 lymph node dissection is the standard of care in localized gastric cancer. However about 40% of patients in East Asia and 70% of patients in Western countries experience recurrence after curative surgical resection of localized gastric cancer. Once recurrence occurs, the prognosis of patients is usually dismal, especially in case of distant metastases. Although many clinical trials of adjuvant treatment were conducted to reduce recurrence of gastric cancer after surgical resection, it was controversial until early 2000s whether adjuvant treatment could improve recurrence-free survival or overall survival in gastric cancer. In early 2000s, adjuvant chemoradiation became the standard of care in the US based on the results of SWOG 9008/INT 0116 trial, where only minor portion of patients underwent D2 lymph node dissection. However, adjuvant chemoradiation was considered not applicable to patients with gastric cancer in East Asia where D2 lymph node dissection is the standard surgical method. Recently, large scale phase III studies including ACTS-GC and CLASSIC trial were conducted in the East Asia. Based on those studies, adjuvant chemotherapy is currently accepted as standard treatment in gastric cancer in the East Asia.

근치적 목적의 절제술 후 II , IIIA 기 비소세포폐암의 Mitomycin - C , Vinblastine , Cisplatin ( MVP ) 복합항암화학요법과 방사선요법의 병용 치료

김태원 ( Tae Won Kim ),이정신 ( Jung Shin Lee ),정병학 ( Byung Hak Jung ),윤환중 ( Hwan Jung Yun ),장대영 ( Dae Young Zang ),이제환 ( Je Hwan Lee ),김성배 ( Sung Bae Kim ),김상위 ( Sang We Kim ),서철원 ( Cheol Won Suh ),이규형 ( K 대한내과학회 1998 대한내과학회지 Vol.54 No.5

Objectives: The poor survival rates among patients receiving surgery alone for stages II and III non-small cell lung cancer prompted several trials of adjuvant therapy after resection. We performed a prospective phase II study in patients with stage II-IIIA non-small cell lung cancer after resection to evaluate the feasibility, activity and toxicity of the postoperative sequential MVP chemotherapy and radiotherapy. Methods: Between February 1991 and May 1995, 60 patients with resected stage II, IIIA non-small cell lung cancer received 2 cycles of MVP combination chemotherapy (Mitomycin-C 6 mg/m², Vinblastine 6 mg/m², Cisplatin 60 mg/m) within 3 weeks after surgery, followed by thoracic irradiation (5,040 cGy after complete resection and 900 cGy booster to microscopically positive resection margin at 1.8 Gy per fraction) within 3-4 weeks after chemotherapy. Results: Forty nine men and 11 women with a median age of 60.5 years (range 33-81 years) were included. During the median follow-up period of 828 days (61-2,015 days), 25 patients had developed recurrence. Among the 25 failures, 3 were local relapse only and 20 were distant metastasis only and 2 had both local and distant sites of recurrence. Three-year overall survival and event-free survival were 43% and 37%, respectively. Neutropenia of grade I-II was observed only in 13 patients. Eleven patient showed grade I-II radiation pneumonitis and 32 had grade I-II radiation esophagitis, Conclusion: Postoperative sequential MVP chemotherapy and radiotherapy in resected stage II-IIIA non-small cell lung cancer is well-tolerated and shows interesting activity,

국소 방사선 치료에 완전 관해된 구개편도에 발생한 골수외 형질세포종

이정화(Jung Hwa Lee),김기성(Ki Seong Kim),김효정(Hyo Jung Kim),박희철(Hee Chul Park),배훈식(Hoon sik Bae),하준욱(Jun Wook Ha),장대영(Dae Young Zang) 대한두경부종양학회 2005 대한두경부 종양학회지 Vol.21 No.2

골수외 형질세포종은 드문 종양으로 두경부에 주로 발생하며 수술 혹은 방사선의 국소 치료로 완치가 가능한 종양이다. 저자들은 구개편도에 발생 후 국소 방사선 치료로 완전 관해된 골수외 형질세포종 1예를 경험하였기에 보고하는 바이다. Extramedullary plasmacytoma(EMP) is a rare tumor that originates as a clone of malignant transformed plasma cells. EMPs make up 4% of all plasma cell tumors and 90% of EMP cases occur in the head and neck area. The diagnosis of EMP is based on the morphologic and immunophenotypical finding of a localized collection of monoclonal plasma cells in the absence of plasma cell proliferation elsewhere. Patients with EMP can be treated by surgery or radiotherapy alone or in combination. EMP has good prognosis but long-term follow-up is critical because local recurrence or systemic progression to multiple myeloma may develop more than 30 years after the initial diagnosis of EMP. We report a case of EMP in palatine tonsil of 21-year old man who was treated successfully by radiotherapy alone.

건강한 한국 성인에서의 백혈구와 호중구 감소증

박진희(Jin Hi Park),서철원(Cheol Won Suh),김우건(Woo Kun Kim),이무송(Moo Song Lee),배창황(Chang Hwang Bae),민영주(Young Joo Min),최성준(Seong Jun Choi),김태원(Tae On Kim),장대영(Dae Young Zang),이제환(Je Hwan Lee),김성배(Sung Bae Kim 대한내과학회 1998 대한내과학회지 Vol.54 No.3

N/A Background: It has been well known that normal leukocyte counts in blood can vary depending on age, gender, other environmental factors and ethnic differences. However, the normal white blood ce11 counts in Koreans has not been settled yet. Over past several years, a large number of patients were referred to the Hematology Clinic of Asan Medical Center (AMC) for evaluation of leukopenia, and most of them were found to have no medical problems other than leukocyte counts less than 4.000/mm3. We performed this study on persons who visited Health 3creening Center to analysis of leukopenic patients and also to establish the normal value of white blood cell counts in Korean. Method: We studied 31,307 persons (19,540 men, 11,767 women, aged 15-90), who visited to Health Screening Center of AMC during the period from January through December 1995. We have carried out retrospective analysis of complete medical record of 2,406 patients (838 men, 1,568 women, aged 20-81) who were found to have leukocyte counts less than 4,000/mm3. And we tried to establish the normal values of leukocyte counts and differential counts of 24,079 adults (15,807 men, 8,272 women, aged 19-90), who were assessed to be healthy at Health Screening Center of AMC. Results: 1) Leukopenia (WBC<4,000/mm3) were found in 2,406 subjects (7.7%) among 31,307 persons screened. 2) Among them, 77 subjects (3%) had medical illness; 39 of them had chronic B or C viral hepatitis, 24 of them had iron deficiency anemia, and other diseases were detected in remaining 14 patients. But other hematologic diseases or significant infectious diseases were not detected. Follow-up study of them has indicated no increased incidence of infection or other hematologic diseases. 3) The total white blood cell counts of 24,097 healthy Korean adults were 3,640-9,870/mm (5,900/mm3) in men, and 3,270-8,400/mm3 (5,264/mm3) in women. Neutrophil counts ranged 1,288-6,866mm3 (3,098/mm3) in men, and 1,180-5,985/mm3 (2,816/mm3) in women. Leukocyte counts were significantly lower in female, but no significant variation was found among age groups. Conclusion: Normal range of leukocyte counts and neutrophil counts of healthy Korean adults were lower than those of white populations. Thus, a new normal values of leukocyte and neutrophil counts should be established in Koreans. And many persons with leukocyte counts less than 4,000/mm3 who are otherwise healthy could be normal.

특발성 혈소판증가증에 관한 최신지견

장대영,박성동,박건욱 동국대학교 의학연구소 2006 東國醫學 Vol.13 No.1

최근에 특발성 혈소판증가증의 분자 생물학적 병인에 관한 많은 발전이 이루어 졌다. 특발성 혈소판증가증의 진단은 수 년전에 개발된 방법으로 다른 질환들을 배제함으로써 이루어진다. 특발성 혈소판증가증은 혈전성 및 출혈성 합병증을 증가시키고, 골수 섬유화증이나 급성 골수성 백혈병으로 진행할 수 있다. 혈관성 합병증을 예방하기 위해 사용되는 골수 억제제 치료법은 혈액학적 악성 질환으로서의 진행을 가속화 시키지 않을까하는 우려로 질병의 위험도에 따라 적절한 치료법을 선택하고 있다. 따라서, 저위험 환자군에서 골수 억제제 치료는 추천되지 않으며, 고위험 환자군에서는 하이드록시유리아와 아스피린의 치료가 효과적인 것으로 알려져 있다. 아나글레라이드나 인터페론-알파는 하이드록시유리아에 내성을 가지거나 투약이 불가능한 환자들에게 2차 약제로 고려될 수 있을 것이다. 산모에 있어서는 인터페론-알파가 더 추천된다. Significant progress in our understanding of the molecular pathogenesis of essential thrombocythemia(ET) has recently been achieved. Unfortunately, the diagnosis of ET still relies on a set of exclusion criteria developed years ago, as recent advances have yet to be evaluated for this purpose. The clinical course of ET is characterized by an increased incidence of thrombotic and hemorrhagic complications and an inherent tendency to progress into myelofibrosis or acute myeloid leukemia (AML). There is concern about undesirable effects of cytoreductive therapy given to prevent vascular events, particularly the risk of accelerating the rate of hematologic transformation. Thus, management involves modification of reversible vascular risk factors and further stratification according to the thrombotic risk. Myelosuppressive agents are not recommended in low-risk patients, whereas controlled studies support the therapeutic value of hydroxyurea (HU) plus aspirin in high-risk cases. Anagrelide or interferon-alpha (IFN-alpha) could be considered as second-line therapy in patients refractory or intolerant of HU, IFN-alpha is preferred in pregnant women.

동종 골수 이식한 백혈병에서 단반복 유전자로 살펴본 혼합 키메라 현상의 의의

장대영,이정신,서철원,이규형,이제환,지현숙,박찬정,한면수,최동원,김정균,최성준,김성배,김상위,김우건,김상희 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.1

연구배경 : 동종 골수 이식한 백혈병에서 키메라 현상의 분석은 착상, 질병 재발과 이식 거부를 이해하는데 도움을 줄 수 있다. 최근 STR을 PCR로 증폭한 검사법에 의해 매우 민감하고 유용하게 혼합 키메라 현상을 검출할 수 있다고 보고되고 있으나, 이 방법의 민감도와 임상적 의의는 아직 완전히 정립되지는 않았다. 따라서 PCR-STR검사법이 혼합 키메라 현상을 민감하게 검출하는지 보고, 동종 골수 이식 후 혼합 키메라 현상의 변화 양상을 관찰하고, 키메라 현상의 임상적 의의를 보고자 하였다. 방법 : 형제로부터 동종 골수 이식한 급성 백혈병 6명과 만성 백혈병 2명의 모두 8명을 대상으로 하였다. 44개 골수 검체에서 phenol/chloroform방법에 의하여 단핵세포 DNA를 추출하였다. DNA는 CTT 삼중체, vWA와 amelogenin시발체를 이용하여 증폭하였다. 증폭 산물은 5% 폴리아크랄아미드 젤에서 전기영동 뒤 은 염색으로 확인하였다. 2명의 DNA를 여러 비율로 혼합하여 상기 검사를 하여 검출 가능 최소 농도를 결정하였다. 결과 : 상기 검사법의 검출 가능 최소농도는 0.25%였다. 혼합 키메라 현상은 8명중 4명에서 관찰되었다. 혼합 키메라 현상은 보인 1명에서 급성 및 만성 이식편대 숙주 질환이 나타났고, 완전 공여자 키메라 현상을 보인 1명에서 만성 이식편 대 숙주 질환이 나타났다. 점진적으로 증가하는 혼합 키메라 현상을 보인 2명은 이식 후 12개월에 질병 재발을 보였으나, 완전 공여자 키메라 현상을 보인 경우엔 재발이 관찰되지 않았다. 결론 : PCR-STR검사법은 동종 골수 이식 후 남아 있는 환자 세포를 검출하고 키메라 현상을 관찰하는데 유용한 방법이다. 또한 이 검사법은 동종 골수 이식 후 재발의 조기 진단, 이식편 대 숙주 질환의 평가와 면역 관용에 임상적으로 응용할 수 있으리라 생각한다. Background : Chimerism analysis after allogeneic bone marrow transplantation (BMT) for leukemia could be helpful understanding of the early marrow engraftment, disease relapse, and graft rejection. Recently, a PCR technique which amplifies short tandem repeats(STR) has been reported to be highly sensitive and reliable in detecting mixed chimerism. But its sensitivity and clinical significance has not been established. The purpose of this study was firstly, to confirm whether a PCR-STR in highly sensitive enough ti assess mixed chimerism, secondly to monitor the changing patterns of mixed chimerism after allogeneic BMT, and lastly to determine correlation between the chimeric status and the clinical outcome. Methods : A study was made eight patients (six with acute leukemia and two with chronic leukemia) who underwent unmanipulated allogeneic BMT along with matched donors. DNA was extracted from mononuclear cells of 44 bone marrow samples using a phenol/chloroform method. Amplification of DNA was done using CSFIPO-TPOX-TH01(CTT) triplex with or without vWA or amelogenin primer. The amplified product was separated on 5% polyacrylamide gel and was confirmed by silver staining. The sensitivity of CTT triplex method was determined by mixing DNA from two person in serial proportion using the same method. Results : The sensitivity for CTT triplex method was 0.25% Mixed chimerism was documented in 4 of 8 patients. ONe of four patients with mixed chimerism developed acute and chronic graft versus host disease (GVHD) and one of four patients with complete donor chimerism also developed chronic GVHD. Two patient with progressive mixed chimerism relapsed at 12 months post-BMT, whereas no patient with complete donor chimerism has relapsed. Conclusion : The study has found that PCR-STR was an effective method for the detecting residual host cell and monitoring the chimeric status after allogenic BMT. PCR-STR can also be clinically applicable in early prediction of relapse, appropriate assessment of GVHD, as well as tolerance after allogeneic BMT.

A Case of Completely Resected Advanced Gastric Carcinoma Following Neoadjuvant Chemotherapy with TS-1

Zang, Dae Young,Park, Seong Dong,Park, Keon Uk 동국대학교 의학연구소 2006 東國醫學 Vol.13 No.1

TS-1은 dihydropyrimidine dehydrogenase를 억제하는 새로운 경구용 fluoropyrimidine 약제이다. 몇몇 연구에서 진행성 위암환자에게 TS-1을 이용한 선행 보조 항암요법의 효과적인 항암효과가 발표 되었다. 본 증례는 TS-1을 이용한 4주기의 선행 항암 화학요법 후 완전절제가 가능했던 진행성 위암 환자에 대한 증례이다. 환자는 85세 남자 환자로 췌장과 대동맥 주위 림프절의 전이소견이 있어 진행성 위암 진단을 받았다. TS-1 (80 mg/day)을 경구로 4주간 투약 후 2주간의 휴약을 1주기로 하여 4주기 동안 투약하였다. 투약 중 1도의 설사와 3도의 빈혈 이외의 특별한 부작용은 관찰 되지 않았다. 4주기의 치료 후 시행한 복부 컴퓨터 단층촬영 상 원병변과 위주위 림프절의 전이병변들은 부분반응을 보였으며, 췌장과 대동맥 주의 림프절의 병변은 관찰되지 않았다. 환자는 위전절제술 및 D2 림프절 절제술을 포함하는 치료적 수술을 시행하였고, 병리학적 병기상 T3, N2, P0, CY0, H0, M0 (Stage IIIB)로 확인되었다. 환자는 수술 후 7개월간 재발 없이 생존하고 있다. TS-1, a novel oral anticancer drug is dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. In some clinical studies, TS-1 has shown effective anti-tumor activity in far advanced gastric cancer patients as neoadjuvant chemotherapy. Here we report our experience with a patient of advanced gastric cancer given 4 cycles of TS-1 as neoadjuvant chemotherapy before complete gastric resection. The patient was an 85-year-old man who was diagnosed with advanced gastric carcinoma that had invaded the pancreas and the paraaortic lymph nodes, before treatment. New oral anticancer drug, TS-1 (80 mg/day) was orally administered for 4 weeks followed by drug-free 2-week period as 1 cycle. Total 4 cycles of TS-1 was administered. No serious drug adverse reaction was observed except for grade 1 diarrhea and grade 3 anemia. After 4 cycles of chemotherapy, follow-up abdominal CT scan showed partial response of primary lesion and regional lymph node metastasis. The lesions in the pancreas tissues and enlarged paraaortic lymph node were not observed. The patient underwent curative surgery, including total gastrectomy and D2 lymph node dissection and the pathologic staging was T3, N2, P0, CY0, H0, M0 (Stage IIIB). The patient has been survived without recurrence for seven months after the surgery.