위암에서 무진행 생존기간을 예측하는데 있어 치료 전 F-18 FDG PET/CT의 유용한 파라미터

김정훈 전북대학교 일반대학원 2013 국내석사

Purpose: I performed this study to evaluate predictive value of pretreatment F-18 FDG PET/CT for progression free survival (PFS) in patients with gastric cancer. Materials & Methods: Of 321 patients with a diagnosis of gastric cancer, I enrolled retrospectively 97 patients (M:F = 61:36, age: 59.8 ± 13.2 yrs), who underwent pretreatment F-18 FDG PET/CT from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured from each case with detectable primary lesion. In remaining non-detectable cases, SUVmax measured from corresponding site seen on gastroduodenoscopy was used for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in clearly distinguishable 50 patients. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find out optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox’s proportional hazard regression methods. Results: Of 97 patients, 15 (15.5%) had a disease progression. Mean follow-up duration was 29.6 ± 10.2 months. Mean PFS of low SUVmax group (≤5.74) was significantly longer than that of high SUVmax group (>5.74) (30.9 ± 8.0 vs 24.3 ± 13.6 months, P=0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (P=0.002, HR 11.03, 95% CI 2.48-49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (P=0.034, HR 3.59, 95% CI 1.10-11.71). Conclusion: In gastric cancer, SUVmax measured by pretreatment F-18 FDG PET/CT has a significant predictive value for PFS. In addition, if MTV is measurable, high MTV is an independent factor for disease progression. 목 적: 위암 환자에서 시행한 치료 전 F-18 FDG PET/CT가 무진행 생존기간을 예측하는데 있어 유용성이 있는지 알아보고자 하였다. 대상 및 방법: 2009년 1월부터 2009년 12월까지 전북대학교병원에서 위암으로 진단 받은 321명의 환자 중 치료 전 F-18 FDG PET/CT를 시행한 97명 (남:여 = 61:36, 나이: 59.8 ± 13.2세)을 대상으로 후향적 연구를 시행하였다. F-18 FDG PET/CT 영상을 육안분석하여 위암병변을 발견할 수 있는 경우에는 일차병소에서 SUVmax (최대표준섭취계수)를 측정하고, 나머지 일차병소를 발견하지 못한 경우에서는 위내시경이나 조영증강 복부 CT 소견을 참고하여 해당부위로 생각되는 부위의 위벽에서 SUVmax를 측정하였다. MTV (대사활성종양부피: F-18 FDG의 섭취가 증가된 종양부피의 총합, cm3)는 F-18 PET/CT 영상에서 육안으로 뚜렷히 구분되는 50명의 환자에서만 측정하여 소집단 분석을 하였다. SUVmax, 병기, 종양의 침범깊이, 그리고 림프절 전이유무를 무진행 생존기간을 예측하는 독립변수에 포함시켜 분석하였다. 수신자판단특성곡선 (Receiver Operating Characteristic Curves)을 이용하여 질병진행에 대한 SUVmax와 MTV의 절단값 (Cut off value)을 구하였다. SUVmax와 MTV 및 무진행 생존기간의 관계를 알아보기 위하여 Kaphlan-Meier 방법과 로그-순위 검정을 통해 단변량 분석을 시행하였고, Cox 비례위험 모델을 이용하여 다변량 분석을 시행하였다. 결 과: 97명의 위암 환자 중 15명 (15.5%)에서 질병진행이 확인되었고 평균 추척기간은 29.6 ± 10.2개월이었다. 높은 SUVmax군 (>5.74)의 평균 무진행 생존기간이 낮은 SUVmax군 (≤5.74)보다 유의하게 길었다 (30.9 ± 8.0개월 대 24.3 ± 13.6개월, P=0.008). 단변량 분석에서 병기 (I기 대 2기, 3기, 4기), 종양의 침범깊이 (T1 대 T2, T3, T4), 림프절 전이유무 및 SUVmax (>5.74 대 ≤5.74)가 통계적으로 유의하게 재발과 관련되어 있었다. 다변량 분석에서는 높은 SUVmax (>5.74)만이 무진행 생존기간을 예측하는데 있어 유일한 나쁜 예후인자였다 (P=0.002, 위험도 11.03, 95% 신뢰구간 2.48-49.05). MTV를 측정할 수 있었던 환자들만을 대상으로 한 소집단 분석에서는 높은 MTV (>16.42)만이 무진행 생존기간을 예측하는 데 있어 유일한 나쁜 예후인자였다 (P=0.034, 위험도 3.59, 95% 신뢰구간 1.10-11.71). 결 론: 위암에서 치료 전 F-18 FDG PET/CT를 통해 측정한 파라미터인 SUVmax와 MTV는 위암 환자의 무진행 생존기간을 예측하는 데 있어서 중요한 예측인자였다. 비록 MTV는 모든 환자에서 측정할 수 없는 단점이 있지만 측정 가능할 경우 MTV만이 질병진행에 관한 독립적인 예측인자였다. 따라서 위암에서 치료 전 시행한 F-18 FDG PET/CT의 파라미터인 SUVmax (>5.74)와 MTV (>16.42)는 환자들의 질병진행을 예측하는데 유용하게 사용할 수 있을 것으로 기대된다.

간외 담도암 고선량률 관내근접방사선치료시 몬테카를로 시뮬레이션을 통한 주변장기의 선량평가 연구

박주경 전북대학교 보건대학원 2013 국내석사

Purpose: The relative dose calculated by MCNPX(Monte Carlo N particle extended) code and the relative dose measured by ionization chamber and solid phantoms evaluated the accuracy comparing with Monte Carlo simulation. The specific effective energy and absorbed dose of bile duct surrounding normal organs could be evaluated by applying MCNPX code the intraluminal brachytherapy of extrahepatic bile duct cancer. Materials and Method: From the center of bile duct, the flux was calculated from 10 mm to 100 mm at intervals of 10 mm using F5 tally mode. The flux was computed using MCNPX code then the numbers were converted into relative dose. In the same way, the relative dose of 192Ir sealed radioactive source was calculated using ionization chamber and solid phantom. We evaluate the accuracy of the results from MCNPX code by comparing the relative dose from MCNPX code and the relative dose from actual measurement. To simulate the actual geometry of the body, we used KMIRD mathematical phantom. In case of bile duct diameter 0.5 cm, 6 cm in length was applied. To check the absorbed dose of normal organs around bile duct, we set the specific effective energy and initial radioactivity to 1 Ci using F6 tally mode from MCNPX code and 104 history. Results: The relative dose calculated by Monte Carlo simulation and the relative dose measured by solid phantoms as distance increases from the center of the source sharply decreased. The difference of the relative dose areas between two methods is the most 1.96%, 0.01% was the lowest point. The specific effective energy and absorbed dose of normal organs that were relatively adjacent to bile duct such as right side of kidney, liver, pancreas, transverse colon, spinal cord, stomach and small intestine were relatively high. On the contrary, the organs that were relatively distant to bile duct such as left side of kidney, spleen, ascending colon, descending colon and sigmoid colon were relatively low. Conclusion: The accuracy of Monte Carlo simulation satisfy the criteria that is the relative error less than 2% suggested by MCNPX code. Therefore, we can trust the result from Monte Carlo simulation when we evaluate 192Ir sealed radioactive source. In addition, the bile duct surrounding normal organs of the specific effective energy and absorbed dose could be evaluated by applying Monte Carlo simulation the intraluminal brachytherapy of extrahepatic bile duct cancer.

갑상선 분화암 환자의 고용량 방사성요오드 치료에서 갑상선호르몬 중단과 재조합 인간 갑상선자극호르몬투여 시 간기능 영향 비교

한연희 전북대학교 일반대학원 2011 국내석사

Background & Objective: An elevated thyroid stimulating hormone level (TSH) is essential to stimulation of the uptake of radioiodine into thyroid remnants and metastases of thyroid cancer in a patient undergoing a high-dose radioiodine therapy. Recently, the use of recombinant human thyroid stimulating hormone (rh-TSH) has increased instead of the conventional thyroid hormone withdrawal (THW). However, the clinical differences of two methods except for the therapeutic effects have not yet been widely proven. The aim of this work was to investigate the influences of the two methods, particularly on liver function. Materials & Methods: I identified 143 evaluable patients who were further divided into two groups, the THW group and the rh-TSH group. Firstly, I reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. I named these liver enzyme levels base AST and base ALT. I also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for a high-dose radioiodine therapy. I named these liver enzyme levels follow-up AST and follow-up ALT. Then, I compared the changes of base and follow-up liver enzyme levels and the other chemistry profiles between the two groups. Results: Both base AST and base ALT levels of the two groups were within normal range and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up liver enzyme levels between two groups showed significant differences. Patients in the THW group had higher follow-up AST and follow-up ALT levels than did those in the rh-TSH group. Comparison of the other chemistry profiles showed that patients in the THW group had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However, there were no statistically significant differences of ALP, total bilirubin, and triglyceride levels between the two groups. Conclusion: In this retrospective analysis of liver function, use of rh-TSH for a high-dose radioiodine therapy showed less effect on liver function and cholesterol profiles than did thyroid hormone withdrawal. This result suggests that rh-TSH can be used effectively and safely, particularly in patients who may have a risk of hepatic failure.

유방암의 술전진단에서 PET/CT-mammography의 유용성: 통상적인 F-18 FDG PET/CT 및 MR-mammography와의 비교

문은하 전북대학교 일반대학원 2011 국내석사

Purpose: The objective of this study was to compare the diagnostic accuracy of an integrated F-18 FDG PET/CT-mammography (mammo-PET/CT) with conventional whole body PET/CT (supine-PET/CT) and MR-mammography for initial assessment of breast cancer patients. Materials and Methods: Forty women (52.0± 12.0 years) with breast cancer who underwent supine-PET/CT, mammo-PET/CT, and MR-mammography from April 2009 to August 2009 were enrolled in this study. I compared the size of the tumor, tumor to chest wall distance, tumor to skin distance, volume of axillary fossa, and number of metastatic axillary lymph nodes between supine-PET/CT and mammo-PET/CT. Next, I assessed the difference of focality of primary breast tumor and tumor size in mammo-PET/CT and MR-mammography. Histopathologic findings served as the standard of reference. Results: In the comparison between supine-PET/CT and mammo-PET/CT, significant differences were found in the tumor size (supine-PET/CT: 1.3±0.6 cm, mammo-PET/CT: 1.5±0.6 cm, p<0.001), tumor to thoracic wall distance (1.8±0.9 cm, 2.2±2.1 cm, p<0.001), and tumor to skin distance (1.5±0.8 cm,2.1±1.4 cm, p<0.001). The volume of axillary fossa was significantly wider in mammo-PET/CT than supine-PET/CT (21.7±8.7 cm3 vs 23.4±10.4 cm3, p=0.03). Mammo-PET/CT provided more correct definition of the T-stage of the primary tumor than did supine-PET/CT (72.5% vs 67.5%). No significant difference was found in the number of metastatic axillary lymph nodes. Compared with MR-mammography, mammo-PET/CT provided more correct classification of the focality of lesion than did MR-mammography (95% vs 90%). In the T-stage, 72.5% of cases with mammo-PET/CT and 70% of cases with MR-mammography showed correspondence with pathologic results. Conclusion: Mammo-PET/CT provided more correct definition of the T-stage and evaluation of axillary fossa may also be delineated more clearly than with supine-PET/CT. The initial assessment of mammo-PET/CT would indicate similar accuracy to MR-mammography for decision of focality and T-stage of primary breast tumor.

소방공무원의 난청에 영향을 주는 요인

장덕하 전북대학교 보건대학원 2021 국내석사

Background: Noise is one of the health hazards of firefighters. In this study, the factors affecting the hearing loss of firemen were investigated. Method: The study was conducted on firemen from 11 fire departments located in Jeollabuk-do from October to November in 2020. 534 respondents to the questionnaire and 128 screening hearing test were conducted and analyzed. Data analysis was performed using the SPSS 27.0 version statistical program. Results: After exposure to noise, acute symptoms such as palpitations, fatigue, sweating, headache, and dyspnea were significantly affected by the career of military service - navy(OR=4.031, p<0.05), and the career of a military service - engineer (OR=2.884, p<0.05). Hearing loss, tinnitus, which are chronic symptoms after exposure to noise, were significantly affected by outside duty for more than 16 years (OR=45.806, p<0.05), and auditory abnormalities during military service (OR=5.082, p<0.05). The presence or absence of hearing loss according to the Korean Hearing Handicap Inventory for the Elderly Screening version (KHHIE-S) questionnaire score was determined for rescue services period of 16 years or more (OR=9.139, p<0.05), emergency medical service period of 11 to 15 years (OR=3.327, p<0.05), the occurrence of auditory abnormalities during military service (OR=16.152, p<0.01) was a significant factor. The factors that significantly affect the worst 4 PTA(Putre tone average 500, 1,000, 2,000, 4,000 Hz) of the screening hearing test were male (β=0.410, p<0.05), emergency medical services 1-5 years (β=0.220, p<0.05), and emergency medical services 11-15 years. (β=0.364, p<0.001), the occurrence of auditory abnormalities during military service (β=0.158, p<0.05). In KHHIE-S questionnaire and screening hearing test, all the left and right ear frequency, except for the left 500 Hz and 1000 Hz frequency, left and right 4 PTA, and Worst 4PTA showed a significant correlation (KHHIE-S score and Rt .500Hz (r=0.291, p<0.01), Rt. 1,000 Hz (r=0.306, p<0.001), Rt. 2,000 Hz(r=0.435, p<0.001), Rt 4,000 Hz (r=0.492, p<0.001), Lt. 2,000 Hz(r=0.281, p<0.01), Lt. 4,000 Hz(r=0.336, p<0.001), Rt. 4 PTA(r=0.498, p<0.001), Lt. 4 PTA(r=0.338, p<0.001), worst 4 PTA(r=0.461, p<0.001)) Hearing loss occurred more when the work period of urban area exceeded 10 years among firemen(χ²= 20.364, p<0.001, 95% CI 2.678 ~ 28.917, OR: 10.6). When comparing firemen and the general public, firemen had more hearing loss (χ²=5.187, p=0.023, 95% CI: 1.085 ~ 3.457, OR: 1.93). Conclusion: In this study, factors influencing the hearing loss of firemen were identified. Through this research, it should be an opportunity for the health care community, academia, government and society to be interested in hearing impairment and hearing loss of firemen. In addition, it is expected that firemen who complain of hearing loss and retired firemen can improve welfare by providing medical expenses for the purpose of treating hearing loss and purchasing hearing aids. 연구배경 및 목적: 소음은 소방공무원의 건강상 유해요인 중 하나이다. 본 연구에서는 소방공무원의 난청에 영향을 주는 요인을 조사하였다. 대상 및 방법: 2020년 10월부터 11월까지 전라북도 소재 11개 소방서의 소방공무원을 대상으로 연구하였다. 설문조사 응답 534명과 선별 청력검사 128명을 시행해 분석하였다. 자료 분석은 SPSS 27.0 버전 통계 프로그램을 이용 하였다. 결과: 소음 노출 후 급성 증상인 심계항진,피로,식은땀,두통,호흡곤란은 군종 해군(OR=4.031, p<0.05), 군보직 공병(OR=2.884, p<0.05)이 유의하게 영향을 주는 요인으로 나타났다. 소음노출 후 만성 증상인 청력감소, 이명은 외근 16년 이상 근무(OR=45.806, p<0.05), 군복무 중 귀 이상 발생(OR=5.082, p<0.05)이 유의하게 영향을 주는 요인이었다. 한국 노인성 난청의 청각장애지수 선별(KHHIE-S) 설문 점수에 따른 난청 유무는 구조 근무기간 16년 이상(OR=9.139, p<0.05), 구급 근무기간 11~15년(OR=3.327, p<0.05), 군복무 중 귀 이상 발생(OR=16.152, p<0.01)이 유의한 영향을 주는 요인이었다. 선별 청력검사의 worst 4P TA에 유의하게 영향을 주는 요인은 성별 남성(β=0.410, p<0.05), 구급 1~5년(β=0.220, p<0.05), 구급 11~15년(β=0.364, p<0.001), 군 복무 중 귀이상(β=0.158, p<0.05)이었다. 한국 노인성 난청의 청각장애지수 선별(KHHIE-S) 설문과 선별 청력검사의 좌측 500Hz, 1000Hz 음역대를 제외한 좌우측 모든 음역대와 좌우 4PTA, Worst 4PTA는 유의한 상관관계를 보였다.(KHHIE-S 점수와 Rt.500(r=0.291, p<0.01) , Rt. 1k(r=0.306, p<0.001), Rt. 2k(r=0.435, p<0.001), Rt 4k Hz(r=0.492, p<0.001), Lt. 2k(r=0.281, p<0.01), Lt. 4k(r=0.336, p<0.001), Rt.PTA(r=0.498, p<0.001), Lt.PTA(r=0.338, p<0.001), worst PTA(r=0.461, p<0.001)) 소방공무원 중 도심 근무기간이 10년 초과한 경우 난청이 더 발생하였다. (χ²= 20.364, p<0.001, 95% CI 2.6780 ~ 28.9175, OR: 10.6) 소방공무원과 일반인을 비교하였을 때 소방공무원이 난청이 더 발생하였다. (χ²=5.187, p=0.023, 95% CI: 1.0853 ~ 3.4576, OR: 1.93) 결론: 본 연구로 소방공무원의 난청에 영향을 주는 요인을 확인했다. 이 연구를 통해 보건의료계, 학계, 정부와 사회에서 소방공무원의 청력 손상과 난청에 관심을 갖는 계기가 되었으면 한다. 또한 난청을 호소하는 소방공무원과 퇴직 소방공무원에게 난청 치료와 보청기 구입을 위한 의료비 지원을 통해 복지의 개선을 기대한다.

Optical Imaging of the MMP Expression and Cancer Progression in an Inflammation-Induced Colon Cancer Model : 염증성 대장암 모델에서 matrix metalloproteinases (MMP)의 발현과 암 성장의 광학 영상화 연구

Jang, Doo-rye 전북대학교 의학전문대학원 2011 국내석사

Purpose: Human colorectal cancer is one of the most common fatal malignancies. The purpose of this study was to use a near-infrared (NIR) fluorescent cyclic His-Try-Gly-Phe peptide to characterize and image the expressions of matrix metalloproteinases (MMPs), which are correlated with cancer promotion, in a mouse model of inflammation-induced colorectal cancer (ICRC). Materials and Methods: My first explored the relationship between the development of colon cancer and the expression of MMPs at the same colonic sites in ICRC models. MMP-2 expression and β-catenin activation in colonic lesions were characterized by immunohistochemical (IHC) staining. After verifying the expressions of the two proteins in induced cancer cells in the colon, c(KAHWGFTLD)NH2 (C6) peptide was prepared by standard Fmoc peptide synthesis to target MMPs. To develop a mouse model of ICRC, mice were administered a single intraperitoneal dose (10 mg/kg body weight) of azoxymethane (AOM) and exposed orally to 2% dextran sodium sulfate (DSS) for one week. In vivo MMP-targeted imaging of Cy5.5-C6 was performed using an IVIS optical imaging system in the ICRC model. Results: The molecular weight of Cy5.5-C6 as determined by maldi-tof-ms analysis was 1954.78 (calculated MW = 1955.23). In the ICRC model, histological examination of colon cancer tissues was performed. After being treated with inducers for some time, cancerous lesions were found to express high β-catenin and MMP-2. The expressions of MMP profiles were correlated with MMP expression with β-catenin activation in the colonic lesions. The in vitro characterization of Cy5.5-C6 showed MMP binding specificity in a cell experiment. In vivo NIR fluorescence imaging showed high accumulation of Cy5.5-C6 in tumors with associated expression of MMP-2 in colonic lesions after intravenous injection. Conclusion: The MMP-2 specificity of Cy5.5-C6 was confirmed by successful inhibition of probe uptake by the tumor in the presence of excess C6 peptide. The use of Cy5.5-C6 to target MMP-2 has the potential to be developed into an effective molecular imaging agent to monitor ICRC progress.