• Molecules and Cells
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• 제46권6호
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• pp.360-373
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• 2023

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.

• Korean Journal of Radiology
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• 제24권12호
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• pp.1284-1292
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• 2023

Objective: We investigated the impacts of computed tomography (CT) added to ultrasound (US) for preoperative evaluation of patients with papillary thyroid carcinoma (PTC) on staging, surgical extent, and postsurgical survival. Materials and Methods: Consecutive patients who underwent surgery for PTC between January 2015 and December 2015 were retrospectively identified. Of them, 584 had undergone preoperative additional thyroid CT imaging (CT + US group), and 859 had not (US group). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for 14 variables and balance the two groups. Changes in nodal staging and surgical extent caused by CT were recorded. The recurrence-free survival and distant metastasis-free survival after surgery were compared between the two groups. Results: In the CT + US group, discordant nodal staging results between CT and US were observed in 94 of 584 patients (16.1%). Of them, CT accurately diagnosed nodal staging in 54 patients (57.4%), while the US provided incorrect nodal staging. Ten patients (1.7%) had a change in the extent of surgery based on CT findings. Postsurgical recurrence developed in 3.6% (31 of 859) of the CT + US group and 2.9% (17 of 584) of the US group during the median follow-up of 59 months. After adjustment using IPTW (580 vs. 861 patients), the CT + US group showed significantly higher recurrence-free survival rates than the US group (hazard ratio [HR], 0.52 [95% confidence interval {CI}, 0.29-0.96]; P = 0.037). PSM analysis (535 patients in each group) showed similar HR without statistical significance (HR, 0.60 [95% CI, 0.31-1.17]; P = 0.134). For distant metastasis-free survival, HRs after IPTW and PSM were 0.75 (95% CI, 0.17-3.36; P = 0.71) and 0.87 (95% CI, 0.20-3.80; P = 0.851), respectively. Conclusion: The addition of CT imaging for preoperative evaluation changed nodal staging and surgical extent and might improve recurrence-free survival in patients with PTC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1115-1118
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• 2016

Background: There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. Materials and Methods: This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis. Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. Results: Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ${\leq}7.4ng/ml$ had the highest diagnostic strength to predict successful ablation in all patients. Conclusions: We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline $sTg{\leq}7.4ng/ml$ is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

• Journal of Nutrition and Health
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• 제26권7호
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• pp.829-838
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• 1993

This study was designed to compare the effect of different dietary fats on the incidence of colorectal tumor, the level of plasma thromboxane B2(TXB2) and fatty acid profiles of platelet and colonic mucosal lipids in N - methyl - N - nitro - N - nitrosoguanidine(MNNG) - treated rats. Male Sprague Dawley rats, at 8 weeks old, were divided into 2 groups and infused intrarectally with saline(control group) or with 2mg MNNG(carcinogen-treated group) twice a week for 3 weeks. Each group was again divided into 4 groups and fed one of four diets(BT, CO, PO, FO) containing dietary fat at 9%(w/w) level for 37 weeks, Dietary fats were beef tallow(7.2%)+corn oil(1.8%) for BT, corn oil(9.0%) for CO, perilla oil(9.0%) for PO, fish oil (6.5%)+corn oil (2.5%) for FO diets. MNNG-treated rats had colonic tumor, while no tumors(adenocarcinoma and adenoma) than others. Tumor sizes in BT-MNNG rats ranged from 2mm papillary form to 15mm of polypoid. However, the size of tumors in PO-MNNG or FO-MNNG rats could not be measured by gross examination. BT-MNNG and CO-MNNG groups were higher in the level of plasma TXB2 and the ratio of c20 : 4/c20 :5 platelet. PO-MNNG groups were lower in the ratio of c20 : 4/c20 : 5(p<0.05) in fatty acid of colonic mucosal lipids suggesting that perilla oil and fish oil could reduce the level of PGE2 and TXB2 by modifying its precursor content and restrain tumor promotion in colon. Effect of perilla oil rich in $\alpha$-linolenic acid on colon carcinogenesis was similar to that of fish oil and thus perilla oil could have a protective effect against colon cancer possibly by inhibiting the production of arachidonic acid metabolite.

• 대한두경부종양학회지
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• 제40권1호
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• pp.1-5
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• 2024

The Bethesda System for Reporting Thyroid Cytopathology (TBSRCT) is crucial for cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations and is effective for clear communication with the referring physicians. The new Bethesda System for Reporting Thyroid Cytopathology, the third edition in 2023, provides several key updates. The most important update is the assignment of only single name for each of the six diagnostic categories: (I) nondiagnostic; (II) benign; (III) atypia of undetermined significance; (IV) follicular neoplasm; (V) suspicious for malignancy; and (VI) malignant. An implied risk of malignancy (ROM) for each of six categories has been updated based on extensively published data since the second edition of TBSRTC in 2017 and offers both an average ROM for each category and the expected range of cancer risk. Estimated final ROM after excluding "Noninvasive Follicular Thyroid Neoplasm with Papillary Like Nuclear Features (NIFTP)" for each of six categories has been updated based on the reported mean decreases in the ROM if excluding NIFTP. For atypia of undetermined significance (AUS) category, the subcategorization is simplified and more formalized into 2 subgroups, AUS-nuclear atypia or AUS-other, based on the implied ROM and molecular profiling. For the pediatric thyroid disease, pediatric ROMs and management algorithms are newly added for the same six reporting categories for this age group. New or revised disease nomenclatures including high-grade follicular-derived carcinoma has been updated according to the recently published 2022 World Health Organization Classification of Thyroid Neoplasms. Brand new two chapters are added including clinical perspectives and imaging studies (Chap. 13) and the use of molecular and other ancillary tests (Chap. 14). The atlas is updated with new images to illustrate more effectively for new disease entity and diagnostic criteria.

• Korean Journal of Radiology
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• 제23권7호
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• pp.763-772
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• 2022

Objective: Preoperative differential diagnosis of follicular-patterned lesions is challenging. This multicenter cohort study investigated the clinicoradiological characteristics relevant to the differential diagnosis of such lesions. Materials and Methods: From June to September 2015, 4787 thyroid nodules (≥ 1.0 cm) with a final diagnosis of benign follicular nodule (BN, n = 4461), follicular adenoma (FA, n = 136), follicular carcinoma (FC, n = 62), or follicular variant of papillary thyroid carcinoma (FVPTC, n = 128) collected from 26 institutions were analyzed. The clinicoradiological characteristics of the lesions were compared among the different histological types using multivariable logistic regression analyses. The relative importance of the characteristics that distinguished histological types was determined using a random forest algorithm. Results: Compared to BN (as the control group), the distinguishing features of follicular-patterned neoplasms (FA, FC, and FVPTC) were patient's age (odds ratio [OR], 0.969 per 1-year increase), lesion diameter (OR, 1.054 per 1-mm increase), presence of solid composition (OR, 2.255), presence of hypoechogenicity (OR, 2.181), and presence of halo (OR, 1.761) (all p < 0.05). Compared to FA (as the control), FC differed with respect to lesion diameter (OR, 1.040 per 1-mm increase) and rim calcifications (OR, 17.054), while FVPTC differed with respect to patient age (OR, 0.966 per 1-year increase), lesion diameter (OR, 0.975 per 1-mm increase), macrocalcifications (OR, 3.647), and non-smooth margins (OR, 2.538) (all p < 0.05). The five important features for the differential diagnosis of follicular-patterned neoplasms (FA, FC, and FVPTC) from BN are maximal lesion diameter, composition, echogenicity, orientation, and patient's age. The most important features distinguishing FC and FVPTC from FA are rim calcifications and macrocalcifications, respectively. Conclusion: Although follicular-patterned lesions have overlapping clinical and radiological features, the distinguishing features identified in our large clinical cohort may provide valuable information for preoperative distinction between them and decision-making regarding their management.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• 제61권11호
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• pp.600-604
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• 2018

Background and Objectives This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). Subjects and Method This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. Results The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: $BRAF^{V600E}$ gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p<0.05). Multivariate analysis revealed that only $BRAF^{V600E}$ mutation was a statistically significant risk factor for malignancy (p<0.05). When $BRAF^{V600E}$ mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. Conclusion Patients with AUS thyroid nodules should undergo $BRAF^{V600E}$ gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.

• Korean Journal of Radiology
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• 제24권9호
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• pp.903-911
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• 2023

Objective: Regrowth after radiofrequency ablation (RFA) of symptomatic large thyroid nodules, initially treated as benign, sometimes turns out to be malignancies. This study aimed to assess the ultrasound (US) characteristics of thyroid nodules initially treated as benign with RFA and later diagnosed as cancers, predictive factors for cancers masquerading as benign, and methods to avoid RFA in these cancers. Materials and Methods: We reviewed the medical records of 134 consecutive patients with 148 nodules who underwent RFA between February 2008 and November 2016 for the debulking of symptomatic thyroid nodules diagnosed as benign using US-guided biopsy. We investigated the pre-RFA characteristics of the thyroid nodules, changes at follow-up after RFA, and the final surgical pathology. Results: Nodule regrowth after RFA was observed in 36 (24.3%) of the 148 benign nodules. Twenty-two of the 36 nodules were surgically removed, and malignancies were confirmed in seven (19.4% of 36). Of the 22 nodules removed surgically, pre-RFA median volume (range) was significantly larger for malignant nodules than for benign nodules: 22.4 (13.9-84.5) vs. 13.4 (7.3-16.8) mL (P = 0.04). There was no significant difference in the regrowth interval between benign and malignant nodules (P = 0.49). The median volume reduction rate (range) at 12 months was significantly lower for malignant nodules than for benign nodules (51.4% [0-57.8] vs. 83.8% [47.9-89.6]) (P = 0.01). The pre-RFA benignity of all seven malignant nodules was confirmed using two US-guided fine-needle aspirations (FNAs), except for one nodule, which was confirmed using US-guided core-needle biopsy (CNB). Regrown malignant nodules were diagnosed as suspicious follicular neoplasms by CNB. Histological examination of the malignant nodules revealed follicular thyroid carcinomas, except for one follicular variant, a papillary thyroid carcinoma. Conclusion: Symptomatic large benign thyroid nodules showing regrowth or suboptimal reduction after RFA may have malignant potential. The confirmation of these nodules is better with CNB than with FNA.

• Radiation Oncology Journal
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• 제26권3호
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• pp.149-159
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• 2008

목 적: 본 연구는 자궁내막암 병기 $1{\sim}2$ 환자에 수술 후 방사선치료의 결과와 예후인자를 분석하여 향후 치료원칙을 결정하는 데 도움을 얻고자 시행하였다. 대상 및 방법: 1991년 1월부터 2005년 12월까지 이화여자대학교 의과대학부속병원에서 자궁내막암으로 진단받고 수술 후 방사선치료를 받은 병기 $1{\sim}2$환자를 대상으로 후향적 분석을 하였다. 전체 환자는 35명이었으며 17명은 자궁절제술과 양측 난소제거술을 시행하였고 18명은 완전한 수술적 병기의 수술을 시행하였다. 골반강 방사선치료를 받은 환자는 17명, 질강내근접치료를 받은 환자는 12명, 골반강 방사선치료와 질강내근접치료를 받은 환자는 6명이었다. 결 과: 추적기간의 중앙값은 54개월이었다. 전체 환자의 5년 생존율은 91.4%, 무병생존율은 81.7%이었다. 저위험군, 중간위험군, 고위험군의 위험군에 따른 5년 생존율은 각각 100%, 100%, 55.6%이었으며 무병생존율은 각각 100%, 70.0%, 45.7%이었다. 국소재발된 환자는 없었으며 5명(14%)에서 원격전이가 발생하였으며 호발부위는 폐, 뼈, 간, 부신, 전복강의 순이었다. 원격전이에 대한 단변량 통계분석에 따르면 위험군, 조직학적 세포형태와 조직학적 등급이 유의성이 있었으며, 다변량 통계분석에 따르면 조직학적 세포형태로서 유두형, 장액형, 그리고 투명세포암은 자궁내막양암과 샘암편평암에 비하여 원격전이율이 높고 생존율이 낮았다. 골반강 방사선치료에 의한 후유증은 장염이 30%에서 나타났으며 다음으로 직장염이었으나 대부분 등급 $1{\sim}2$로 등급 $3{\sim}4$의 후유증은 발생하지 않았다. 결 론: 수술 후 골반강 방사선치료 혹은 질강내근접치료를 시행한 자궁내막암 병기 $1{\sim}2$환자들의 경우 저위험군과 중간위험군은 국소제어율과 생존율이 높았으나, 고위험군은 골반강 방사선치료를 시행하여 국소제어율은 높으나 원격전이율이 높고 생존율이 낮았다. 따라서 고위험군은 방사선치료와 동시에 항암화학요법이 요구된다. 중간 위험군의 더 효율적인 치료를 위하여 많은 환자를 대상으로 골반강 방사선치료와 강내근접치료를 비교하는 전향적 무작위연구가 필요하다.

• 대한핵의학회지
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• 제37권2호
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• pp.110-119
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• 2003

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 $50{\pm}11$세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39, 평균연령 $50{\pm}11$세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 $50{\pm}12$세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 $77{\pm}3MBq$)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색 체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계산하였다. 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 $0.012{\pm}0.3Gy,\;1.66{\pm}25Gy$였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고(1.21: 166 rad, p<0.0001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다($0.58{\pm}0.1\;vs.\;0.56{\pm}0.1$ rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 $13.3{\pm}1.9GBq\;(9.7{\sim}16GBq)$ 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 $13.8{\pm}2.1GBq(10.4{\sim}16.3GBq)$로 유의한 차이가 얻었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 $1.78{\pm}0.03Gy$였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 $1.54{\pm}0.03Gy$로 유의하게 낮았으나 (p=0.01), 두 측 정치 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 13명(30.2%), 고용량 치료군 15명중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(모두 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.