물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가

김정철,윤정한,범희승,제갈영종,송호천,민정준,정환정,김성민,허영준,이명호,박영규,정준기 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

목적 : 분화갑상선암 환자에 대한 방사성옥소(I-131) 치료는 재발율과 사망률을 감소시키는 효과적인 치료법이지만, 치료용량을 증가시킴으로써 치료율을 향상시킬 수 있는지에 대해서는 아직 논란이 있다. 본 연구에서는 최대허용선량 치료법의 효용성을 검증하고자 하였다. 대상 및 방법 : 임상적 병기가 제3, 4병기이고, 6개월 이후에 I-131 전신스캔(이하 IWBS)과 혈중 thyroglobulin (이하 Tg), anti-thyroglobulin antibody (이하 ATA), 초음파검사 (이하 US) 및 F-18 FDG PET 등을 통해 치료여부를 확인할 수 있었던 58명(남:여=9:49, 평균연령 50±11세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39), 평균연령 50±11세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 50±12세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 77±3 MBq)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계사하였다. 완전치유(complete response, 이하 CR)는 IWBS에서 병소가 없어지고, 혈중 Tg치가 1 ng/mL 이하로 감소한 경우로 정의하였으며, 부분치유(partial response, 이하 PR)는 IWBS에서 병소가 없어졌더라도 혈중 Tg, ATA치가 높거나, US 또는 PET 검사에서 병소가 남아있는 경우로 정의하였다. 치료후 IWBS에서 병소가 오히려 증가하거나 변함없는 경우는 없었다. 방사성옥소 치료에 의한 부작용은 입원기간 중 타액선이 현저하게 붓고 통증이 있거나, 구토를 심하게 하는 경우, 그리고 퇴원후 1개월째 백혈구수가 20% 이상 감소한 경우로 정의하였다. 결과 : 양 군간에 연속적인 수치변화를 비교하는 경우는 paired t-test를 이용하였으며, 대상군간 치료효과와 부작용의 비교는 chi-square test를 이용하였다. p값 0.05 미만을 통계적으로 유의한 차이로 인정하였다. 고용량군 환자 모두에서 추적용량과 치료용량의 방사성옥소 투여 후 혈액의 피폭선량은 각각 0.012±0.3 Gy, 1.66±25 Gy였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고 (1.21: 166 rad, p<0.001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다(0.58±0.1 vs. 0.56±0.1 rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 13.3±1.9 GBq (9.7 ~ 16 GBq) 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 13.8±2.1 GBq (10.4 ~ 16.3 GBq)로 유의한 차이가 없었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 1.78±0.03 G였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 1.54±0.03 G로 유의하게 낮았으나 (p=0.01), 두 측정치 간에는 유의한 상관관계(r=0.86, p=0.01)가 있었다. 저용량 치료군 43명 중 22명(51.2%)에서 완전치유를 보였고 21명(48.8%)에서는 부분치유를 보인 반면 고용량 치료군 15명 중 12명(80%)에서 완전치유를 보였고 3명(20%)에서만 부분치유를 보여 고용량 치료군에서 유의하게 높은 완전치유를 얻을 수 있었다(p=0.05). 한편 부작용 발생빈도는 저용량 치료군 43명 중 13(30.2%), 고용량 치료군 15명 중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(p>0.05). 결론 : 혈중소실곡선으로부터 MPD를 결정하고 이를 토대로 환자 개개인별로 적절한 선량을 선택하여 치료하는 방법은 부작용을 최소화하면서도 치료효과를 높일 수 있는 매우 유용한 치료법이며, 고위험군 분화갑상선 암 환자에게 가장 적절한 치료법이라고 사료되었다. Purpose: Radioiodine (1-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up 1-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-does group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose 1-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

한국 여성 유방암 환자에서 종양내 p53 종양억제 유전자 변이에 관한 연구

제갈영종(Young Jong Jaegal),윤정한(Jung Han Yoon),홍석진(Suk Jin Hong),김신곤(Shin Kon Kim),오상진(Sang Jin Oh) 대한외과학회 1995 Annals of Surgical Treatment and Research Vol.49 No.1

방사선 요오드-131의 국소주입에 의한 양성 갑상선 결절의 치료

제갈영종(Young Jong Jaegal),범희승(Hee Seoung Boom),윤정한(Jung Han Yoon),임동표(Dong Pyo Lim),하일주(Il Joo Ha) 대한두경부종양학회 2001 대한두경부 종양학회지 Vol.17 No.2

Background and Objective: Percutaneous ethanol injection therapy has been used in the treatment of the benign thyroid diseases. Although the reported side-effects of the therapy was mild and transient, some side-effects including local or radiating pain are troublesome to the patients. Radioactive iodine-131( Ra?131I) also has been effectively and safely used for management of the benign thyroid diseases. So we developed the percutaneous intranodular injection therapy of Ra?131I as an alternative of percutaneous ethanol injection therapy. Materials and Methods: From December 1998 to October 1999, we treated 29 outpatients (25 women and 4 men, mean age: 47±12 years). Inclusion criteria were follows; age >30 years, cytologically benign, with normal thyroid function, cold nodule on thyroid scintigram, solid or mixed natured nodules in sonographical evaluation. Nodular volume was estimated by sonography according to the ellipsoid formula. Ra?131I (0.1mCi/ml) was administered in a single dose injection. Follow-up studies every 3 months consisted of full history, thyroid function test, and sonography. We determined the therapeutic response is effective if the volume reduction of the nodule occurred above 30%. Results: After at least 3 months follow-up, 11 patients showed effective response, 12 patients showed minimal or unchanged response and 6 patients showed progression. Although side-effects such as injection pain, febrile reaction, and hormonal changes were absent, an infectious complication in injection site was developed from 1 case. Conclusion: Although we need a more prolonged follow-up to evaluate the delayed sequelae, we can suggest that percutaneous intranodular injection therapy of Ra?131 I may be an attractive non-surgical treatment in selected cases of benign thyroid nodules.

유방의 수질암

제갈영종,조용근,윤정한,김종순 中央醫學社 1997 中央醫學 Vol.62 No.7

Medullar carcinoma of breast which have been referred to as solid circumscribed carcinoma represents some characteristics different from ductal carcinoma in breast. To reveal these characteristics is important in order to manage more accurately the patients with medullar carcinoma. However the characteristics of Korean medullar breast carcinoma were not clarified yet. So we analyzed the our experience for medullar carcinoma to determine its clinic pathological characteristics. We evaluated 16 patients from January, 1989 to December, 1996. The results were follows ; Medullar carcinoma was developed at rate of 4.3 % in breast cancers. Mean age was 46.7 years and most of them(62.5 %) was belonged to stage La. Negative expression of steroid receptor was more common and Diploidic pattern was common in flow cytometric study, compared with ductal carcinomas. All patients in this study was alive without recurrence in follow-up period(4 months 5 years). In conclusion, we can suggest that medullar carcinoma of breast has a less aggressive behavior than invasive ductal carcinoma in spite of some bizarre histological characteristics.

Medroxyprogesterone(Farlutal^(�))을 이용한 재발성 유방암의 치료

제갈영종,윤정한,정상우 中央醫學社 1995 中央醫學 Vol.60 No.1

Endocrine therapy is the oldest form of systemic treatment of advanced breast cancer and consisted of ablation therapy and adding agents which reduce the estrogen effect. Improvements in endocrine therapy have been achieved by better ways of selecting patients likely to respond, by advent of new drugs with less-side effects and better understanding of the mechanism of action. Progestin as an adding agent was shown to have antiestrogen effects and have a possibility as an effective treatment modality for breast cancer. Although many reports at early stage showed its therapeutic effects was minimal due to short duration of response and unremarkable results, progestin has become a promising endocrine modality for the treatment of metastatic breast cancer through the developments of new synthetic progestins and the use with proper dosage. So, we tried to evaluate the therapeutic results of Medroxyprogesterone(Farlutal), one of the most widely used synthetic progestins, in management of metastatic breast cancer patients. The results were follows 1. The number of patients in this study was 9 cases which had 10 recurrent organ sites consisted of 7 bones, 1 lung, 1 liver and 1 lymph nodes. 2. The therapeutic response rate with Farlutal^(�) was marked in cases having bone metatstasis(85.7 %). 3. Following administration of Farlutal^(�), improvement of subjective symptoms such as pain relief, well-being sense and increased appetite were notified in majority of the patients. 4. Other toxic side-effects than weight gain in 3 cases and vaginal bleeding in 1 case were not noted. So, We concluded Farlutal^(�) is a safe and effective hormonal agent that has marked therapeutic efficacy in cases with bone metastasis and improves many disabling complaints in patients with metastatic breast cancer.

갑상선에 발생한 과립세포종양 1예

박종훈(Jong Hoon Park),강효(Hyo Kang),조문형(Mun Hyeong Cho),윤정한(Jung Han Yoon),제갈영종(Young Jong Jaegal),박민호(Min Ho Park) 대한두경부종양학회 2006 대한두경부 종양학회지 Vol.22 No.1

Granular cell tumor is not rare and is a well recognized entity which has a wide anatomic distribution, with roughly one half of the lesions found in the head and neck. However, occurrence in the thyroid is extremely rare and has not been described well as surgeon's view. The authors have recently experienced a case of multifocal granular cell tumor of the thyroid in a 26-year-old women presented with painless mass in the anterior neck area and fatigue. So, we present this case with the review of literatures.

뇌 전이를 보인 갑상선 유두암 1예

김세종(Sae Jong Kim),김재휴(Jae Hwu Kun),제갈영종(Young Jong Jaegal),윤정한(Jung Han Yoon) 대한두경부종양학회 1996 대한두경부 종양학회지 Vol.12 No.2

갑상선 유두암에 의한 뇌전이는 극히 드물게 발견되어며 그 진단 및 치료방법의 설정이 아직 확립되어 있지 못한 상태이다. 저자들은 갑상선 유두암으로 5년전 갑상선 전절제술을 시술받고 갑상선 호르몬 복용을 하고 있던 24세의 남자에서 간헐적인 발작을 일으킨 전두골내 병소가 갑상선 유두암의 전이에 의한 것임을 조직학적으로 확인할 수 있었다. 이 병소는 전신 요오드 주사상에서는 나타나지 않았지만 Brain CT 및 MRI 소견으로만 병변의 진단이 가능하였으며 stereotactic cranitomy에 의한 종양제거로 비교적 만족스러운 결과를 얻어 현재 밀착추적중에 있다. Brain metastasis is extremely rare in thyroid papillary carcinoma which has an indolent clinical course and results in good prognosis. A 24-year-old man presenting with seizure attack is described. He had been treated under the diagnosis of thyroid papillary carcinoma with total thyroidectomy, postoperative internal radiation with radioactive iodine, and thyroid hormone replacement. Although 99m Tc brain spect and 131 I whole body scan did not revealed any significant lesion, brain CT and MRI showed lcm sized mass in frontal lobe. Stereotactic craniotomy and removal of the tumor, which was histologically proven metastatic lesion from thyroid papillary carcinoma, was done with satisfactory improvement.

Tc-99m MIBI 신티그래피를 이용한 유방암의 생물학적 특성에 관한 연구

최일(Il-Choi),제갈영종(Young-Jong Jaegal),윤정한(Jung-Han Yoon),박창수(Chang-Su Park),범희승(Hee-Seung Bum) 대한외과학회 1999 Annals of Surgical Treatment and Research Vol.57 No.1

외상성 장파열환자의 치료에서 새로운 Aminoglycoside 항생제 Astromicin Sulfate(Fortimicin^(�))의 효과

김신곤,제갈영종,송은규 中央醫學社 1994 中央醫學 Vol.59 No.4

Fluid resuscitation & appropriate antibiotic therapy are important aspects of the preparation of panperitonitis patients with traumatic intestinal rupture. In these cases, Antibiotic therapy is initiated empirically based on the likely microorganisms to be found at surgery. The peritoneal infections caused by intestinal rupture are almost always polymicrobial, containing a mixture of aerobic and anaerobic bacteria. Although the gold standard of therapy for these peritoneal infection consists of a combination of an aminoglycoside and an antianaerobic agent, there are many problems in widespread use of aminoglycoside because of well-known nephrotoxicity and ototoxicity. Fortimicin�, an new aminoglycoside antibiotic, has been reported to be-more potent and safe with reduced toxicities. So, we tried to evaluate the efficacy and safety of Fortimicin� in management of panperitonitis patients with traumatic intestinal rupture. The results are follows; 1. The evaluated panperitonitis patients were 13 cases due to jejunal rupture, 8 cases ileal rupture, 3 cases colon rupture, and 1 case duodenal rupture. 2. Fortimicin� was most effective in management for jejunal rupture, and overall efficacy rate was 88 %. 3. Bacterial cultures from the contaminated peritoneal fluids were positive in 3 cases 4. Significanct side-effects following administration of Fortimicin� were not notified in this study. So, we concluded that Fortimicin� is an effective and safe antibiotic in managements for traumatic intestinal ruptures.

유방암 근치절제술후 즉시유방재건술의 유용성 및 안정성에 대한 연구

윤정한(Jung Han Yoon),제갈영종(Young Jong Jaegal),정상영(Sang Young Chung) 대한외과학회 1998 Annals of Surgical Treatment and Research Vol.54 No.6