• Journal of Chest Surgery
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• 제26권3호
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• pp.214-218
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• 1993

Extensive lymphnode dissection combined with thoracic esophagectomy improved prognosis of esophageal cancer, but there is still high postoperative recurrence rate. The immunologic capacity of esophageal cancer patients is compromised by surgery and adjuvant chemotherapy. Therefore immunological therapy for esophageal cancer patients seems rational. We have adopted postoperative immunochemotherapy since 1988. From 1988 to 1992, 31 patients with thoracic esophageal cancer underwent esophagectomy and radical lymphnode dissection, and selected patient with early esophageal cancer and unfit for thoracotomy underwent transhiatal esophagectomy in Korea University Hospital. Mean age of patients was 56 years. There were 28 squamous cell cancers, 2 adenocarcinomas and one mixed tumor. There were 4 stage I, 3 stage II, 18 stage III, and 6 stage IV cases. There were no opeartive death. Postoperative complications included anastomotic leakage in 9%, pneumonia 3 %, cylothorax 3%, recurrent laryngeal neve paresis in 3% of all patients. Curative resection group[n=19] received immunotherapy. Noncurative resection group[n=12] received postoperative immunochemotherapy, including PS-K, CDDP, and 5-FU. Operative survivors were followed from 4 months to 5 years. There were 3 lost of follow-up. Actuarial survival rate is 79% to one year, 54% to two years and 27% to five years.In conclusion, an transthoracic esophagectomy combined with systematic lymph node dissection and postoperative immunochemotherapy could improve survival rate for esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4039-4044
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• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 1999년도 제39회 춘계학술발표대회
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• pp.59.1-59.1
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• 1999

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1993년도 학술대회지
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• pp.61-65
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• 1993

To find out the mechanisms of anticancer effect of ginseng, we performed prospective randomized study for the 39 patients with stomach cancer who had undergone radical subtotal or total gastrectomy and postoperative immunochemotherapy with PMF from July 1991 to November 1991 at Department of Surgery, Seoul National University Hospital. The patients were randomly divided into study and control group: the study group was administered with powdered red ginseng of 5400mg daily dose for 12 months postoperatively, the control group was simply followed-up. There were no significant differences between study and control group in twelve months postoperative body weights, triceps skin fold, hemoglobin. albumin, total protein, PNI, total WEC and lymphocyte count, and T-cell percentage (p>0.05). The results of preoperative DNCB skin test of study group was (0) for 8 patients and (+) for 12 patiens. but after operation, it showed the tendency of decreasing (0) and (+) ratio and increasing tendency of (++) ratio (p<0.05), but those of control group showed no increasing tendency of the degree of positive DNCB skin test. From the above results, we could conclude that ginseng had anti - cancer effect by the way of immune mechanism and could be an adjunct to the patients with stomach cancer postoperatively.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9667-9672
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• 2014

Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

• Journal of Gastric Cancer
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• 제1권1호
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• pp.17-23
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• 2001

Purpose: The purpose of this study is to analyze the clinicopathologic characteristics of gastric cancer patients and to evaluate the survival and prognostic factors and effect of immunochemosurgery for gastric cancer patients. Materials and Methods: The clinicopathologic characteristics were analyzed for 12,277 consecutive patients who underwent operation for gastric cancer from 1970 to 1999. We also evaluated the survival and prognostic factors for 9,262 consecutive patients from 1981 to 1996. The prognostic significance of treatment modality [surgery alone, surgery+chemotherapy, surgery+immunotherapy+chemotherapy (immunochemosurgery)] were evaluated in stage III gastric cancer. Results: The 5-year survival rate (5-YSR) of overall patients was $55.8\%$, and that of patients who received curative resection was $64.8\%$. The 5-YSRs according to TNM stage were $92.9\%$ for Ia, $84.2\%$ for Ib, $69.3\%$ for II, $45.8\%$ for IIIa, $29.6\%$ for IIIb and $9.2\%$ for IV. Regarding adjuvant treatment modality, significant survival difference was observed in stage III patients. The 5-year survival rates were $44.8\%$ for immunochemosurgery group, $36.8\%$ for surgery+chemotherapy group and $27.2\%$ for surgery alone group. Curative resection, depth of invasion and lymph node metastasis were the most significant prognostic factors in gastric cancer. Conclusion: Consequently, early detection and curative resection with radical lymph node dissection, followed by immunochemotherapy especially in patients with stage III gastric cancer should be recommended as a standard treatment principle for patients with gastric cancer.

• Clinical and Experimental Pediatrics
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• 제45권8호
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• pp.1007-1015
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• 2002

목 적: 혈구 탐식 조직구 증식증은 양성 질환으로는 드물게 치명율이 높은 질환으로, 발열, 간비장 종대, 림프절 종대 등의 증상이 있고, 검사 소견에서 양성의 혈구 탐식 조직구가 나타난 경우 진단되나 치료가 혼란스러운 경우가 많다. 골수 검사상 양성의 혈구 탐식조직구가 나타난 예들의 임상적 특징을 분석하여 진단 및 치료 방향과 예후 판정에 도움이 되고자 이 연구를 시행하였다. 방 법 : 1995년 1월부터 2001년 11월까지 계명대학교 동산병원에서 골수 검사상 양성의 혈구 탐식 조직구가 나타난 환아 30례를 대상으로, 특징적 임상 증상, 진찰 소견, 혈액 검사 소견, 골수 검사 소견, 치료 방법과 예후에 대하여 임상 기록지를 후향적으로 분석하였다. 또한 골수 도말에서 혈구 탐식 조직구의 수에 따라 a few, some, many로 나누어 환아의 예후와 비교하였다. 결 과 : 골수 검사상 양성 혈구 탐식 조직구를 보인 예들을 분석한 결과 이들의 연령 분포는 2개월에서 15세로, 평균 연령은 5.6세였고, 남녀비는 2.3 : 1로 남아가 많았다. 입원 당시 증상으로는 발열이 가장 많았으며, 호흡기 증상, 위장관 증상 등의 순이었고, 평균 발열 기간은 19.5일이었으며, 진찰 소견은 간비종대, 피부 발진, 림프절 비대 순으로 많았다. 혈액 검사 소견상 백혈구 감소증이 23례(76.7%)로 가장 많았고, 혈소판 감소증이 16례(53.3%), 빈혈이 15례(50.0%), 간기능 검사 이상이 15례(50.0%)로 나타났다. 기저 질환으로 급성 림프구성 백혈병, 악성 림프종 등 면역 저하된 상태가 5례였고, 건강했던 경우가 25례 였으며, 관련 질환의 종류로는 패혈증, 폐렴, 전염성 단핵구증 등의 순이었고, 원인으로는 세균이 많았으며, 바이러스로는 EBV가 4례였고, candida가 1례였다. 골수 도말 소견상 세포 충실도가 정상이 25례(83.3%)였고, 5례(16.7%)에서 감소되어 있었으며, 혈구 탐식 조직구의 수에 따라 분류하였을 때, some이 15례(50.0%), many가 9례(30.0%), a few가 6례(20.0%)이었다. 치료는 보존 요법, 항생제와 항바이러스제, 항진균제, 면역 글로불린, steroid, etoposide, cyclosporine 등의 병용 요법을 시행하였다. 사망율은 30명 중 8명으로 26.7%였으며, 연령이 낮은 군과 혈구 탐식 조직구 수가 some 이상인 경우에 사망률이 높았다. 결 론 : 고열, 간비종대, 범혈구 감소증과 간기능 이상 등의 소견을 보이는 환아에서 조기에 골수 검사를 시행하여 혈구 탐식 조직구가 보일 때, 원인 치료 및 대증 요법과 함께 면역 화학 요법을 시행하는 것이 예후에 도움이 될 것으로 생각되며, 골수 소견과 예후와의 관계는 지속적인 연구 관찰이 필요할 것으로 사료된다.

• Journal of Gastric Cancer
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• 제5권1호
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• pp.52-56
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• 2005

위암은 국내에서 발생 빈도가 가장 높은 암으로서 근치적 절제술 및 확대 영역 림프절 절제술의 도입과 더불어 술후 보조 항암화학요법 및 면역요법 등의 이용으로 최근 치료성적의 향상을 보이고 있다. 그러나 수술적 치료를 포함한 치료법의 발전에도 불구하고 다양한 형태의 재발을 경험하게 되고, 대부분의 재발은 3년 이내에 일어난다. 재발양상으로는 크게 국소재발, 원격재발, 복막재발 등이 있으며, 여러 가지 재발양상이 한꺼번에 보이는 경우도 있다. 이 중 국소재발의 호발 부위로는 림프절($48\%$), 문합부($32\%$, 잔존 위($20\%$)의 순으로 보고되고 있다. 증례: 51세의 여자 환자로 1999년 10월 진행성 위암으로 근치적 위전절제술을 시행 받았고, 당시 병기는 T3N1M0(IIIa,AJCC 1997)이었다. 수술 후 10회의 보조적 정맥 주사용 항암화학요법 및 경구용 항암화학요법을 2년간 실시하였고, 외래를 통한 추적검사상 약 5년간 재발을 보이지 않았으나 2004년 9월 시행한 내시경상 Kim's tie 부근공장에서 궤양성 병변을 발견하고 조직검사를 시행, 병리학적으로 낮은 분화도를 보이는 인환 세포암종 형태의 위선암 재발로 진단하고 수술을 시행하였다. 수술 방법은 Kim's tie 위치를 포함해 근위부 6.5 cm, 원위부 4 cm의 절제연을 두고 공장부분 절제술을 시행하였다. 수술 당시 다른 복부장기로 전이는 없었으며 전이성 복수도 없었다. 수술 후 별다른 합병증 없이 회복하였으며 보조 항암화학요법 제제로써 TS-1을 사용하며 외래 통한 추적검사 중이다.

• Journal of Yeungnam Medical Science
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• 제38권3호
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• pp.208-218
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• 2021

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe, life-threatening inflammatory condition if untreated. We aimed to investigate the etiologies, outcomes, and risk factors for death in children and adults with HLH. Methods: The medical records of patients who met the HLH criteria of two regional university hospitals in Korea between January 2001 and December 2019 were retrospectively investigated. Results: Sixty patients with HLH (35 children and 25 adults) were included. The median age at diagnosis was 7.0 years (range, 0.1-83 years), and the median follow-up duration was 8.5 months (range, 0-204 months). Four patients had primary HLH, 48 patients had secondary HLH (20 infection-associated, 18 neoplasm-associated, and 10 autoimmune-associated HLH), and eight patients had HLH of unknown cause. Infection was the most common cause in children (14/35, 40.0%), whereas neoplasia was the most common cause in adults (13/25, 52.0%). Twenty-eight patients were treated with HLH-2004/94 immunochemotherapy. The 5-year overall survival (OS) rate for all HLH patients was 59.9%. The 5-year OS rates for patients with primary, infection-associated, neoplasm-associated, autoimmune-associated, and unknown cause HLH were 25.0%, 85.0%, 26.7%, 87.5%, and 62.5%, respectively. Using multivariate analysis, neoplasm-induced HLH (p=0.001) and a platelet count <50×10⁹/L (p=0.008) were identified as independent risk factors for poor prognosis in patients with HLH. Conclusion: Infection was the most common cause of HLH in children, while it was neoplasia in adults. The 5-year OS rate for all HLH patients was 59.9%. HLH caused by an underlying neoplasm or a low platelet count at the time of diagnosis were risk factors for poor prognosis.

• 대한골관절종양학회지
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• 제11권2호
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• pp.141-147
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• 2005

목적: 악성 흑색종의 치료 중 가장 중요한 것은 외과적 전절제술이며, 수술시 광범위 절제술을 시행한다. 저자 등은 광범위절제와 면역화학요법을 시행한 후 각 병기별 5년 생존율을 알아보고 예후에 영향을 주는 요인을 주는 요인들을 분석하고자 한다. 대상 및 방법: 1995년 3월부터 2003년 8월까지 악성 흑색종으로 진단 받았던 35명(남자 17명, 여자 18명)을 대상으로 광범위절제술과 면역화학요법을 시행한 후 추시 관찰하였다. 절제술은 종양의 크기나 피부층의 침범정도와 상관없이 종양의 변연으로부터 2 cm으로 하였고, 절제술 후 덮이지 않는 피부 결손부는 피판 이식술이나 전층 피부 이식술을 이용하였다, 면역화학요법으로는 dacarbazine (DTIC) 400 mg과 인터페론-${\alpha}$ 300만 IU를 병용 투여 하는 방법을 사용하였다. 면역화학요법은 III기 이상의 환자에게 시행하였고, 병기는 2002년 개정된 AJCC 병기를 이용하여 판정하였다. 또 이들 환자들에 대해 국소재발과 국소전이, 그리고 원격전이여부를 조사하였고, 각 병기별 5년 생존율을 조사하였다. 결과: 발생부위는 족부가 15명(42.8%)으로 가장 많았고, 족관절부 5명(14.2%), 하퇴부 2명(5.7%), 대퇴부 2명(5.7%), 수부에 5명(14.2%)이었다. 병기별 발생빈도는 IA 8명(22.8%), IB 9명(25.7%), IIA 4명(11.4%), IIB 2명(5.7%), IIIA 1명(2.8%), IIIB 2명(5.7%), IIIC 2명(5.7%) 그리고 IV기는 7명(20.0%) 이었다. 각 병기별 5년 생존율은 I기에서 94.1%, II기에서 66.8%, III기에서 40%, IV기에서 14.3%로 나타났다. 결론: 악성 흑색종은 III기 이상에서는 5년 생존율이 낮았다. 악성 흑색종의 치료는 초기에 진단하여 병기에 따라 치료의 방법을 달리하므로 수술전 병기의 확인이 매우 중요하다. 광범위 절제연에 대해서는 종양 두께에 따라 1~3 cm의 절제연으로 광범위 절제를 권유한다.