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研究生：	林建良 Lin, Chien-Liang
論文名稱：	發炎性腸病的嚴重度與其所用的藥物對日後形成各種血液癌症的影響 The Impact of Inflammatory Bowel Disease Severity and Medication on Subsequent Specific Hematologic Neoplasm
指導教授：	林聖翔 Lin, Sheng-Hsiang
學位類別：	碩士 Master
系所名稱：	醫學院 - 臨床醫學研究所碩士在職專班 Institute of Clinical Medicine(on the job class)
論文出版年：	2016
畢業學年度：	104
語文別：	英文
論文頁數：	39
中文關鍵詞：	發炎性腸炎、血液癌症、藥物
外文關鍵詞：	Inflammatory bowel disease, hematologic malignancy, drugs
相關次數：	點閱：72 下載：5
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查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

目的：本研究是要探討發炎性腸炎的病人增加血液癌症的風險，是因為疾病本身或是其所用的藥物所致。
實驗設計：我們執行一個回顧性的世代研究。從臺灣健保資料庫中選取於2000年至2009年被診斷為發炎性腸炎的病人，並且曾經使用過治療的藥物，當作實驗組。我們利用Cox比例風險模式合併競爭風險分析的方法來比較發炎性腸炎的病人和一般族群得到血液癌症的風險性。其中血液癌症又分為骨髓性白血病、淋巴性白血病、何杰金氏淋巴瘤、非何杰金氏淋巴瘤和多發性骨髓瘤，分别計算它們的風險性。再者，我們以住院的頻率和追踪的時間來代表疾病的嚴重度。最後，用於治療發炎性腸炎的五類藥物比較其將來得到血液癌症的風險。
結果：由2000年至2009年，我們收錄了3,547個發炎性腸炎的病人。其中男性佔了58.8%, 而在18-44歲, 45-64歲和大於65歲的比例分別是42.6%, 31.4%和26.0%。在追踪的時間内有57位被診斷血液癌症。當細分個各癌症别時，其調整後的風險比為：骨髓性白血病8.04，淋巴性白血病3.92和非何杰金氏淋巴瘤4.12。而發炎性結腸炎的病人未使用過藥物或使用過一類藥物比上非發炎性結腸炎的病人將來得到血液癌症的風險多6.36倍(95% CI: 3.66-11.05)和4.08倍(95% CI: 2.45-6.79)。至於藥物，並沒有任何一類的藥物會影響將來血液癌症的形成。
結論：本研究發現在亞洲的族群中, 血液癌症風險的增加與發炎性腸炎的自然病程有關，與其所用的藥物無關。

Purpose: The present study aimed to determine the increased risk of hematologic malignancy induced by inflammatory bowel disease (IBD) or by its used drug.
Experimental Design: We set a retrospective cohort study. Patients who had been diagnosed as IBD during 2000-2009 and had prescribed drugs for IBD from National Health Insurance Research Database (NHIRD) in Taiwan were enrolled in experimental group. The Cox proportional hazard regression analysis with adjust and competing risk regression (CRR) was computed to compare the risk of hematologic malignancies in IBD and non-IBD patients. The specific hematologic malignancies, such as myeloid leukemia, lymphoblastic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma, were clarified the individual risk in IBD patients. Furthermore, we want to know the relationship between severity which was substituted by frequency of admission and follow-up duration and the risk of IBD. Finally, five classes of IBD drugs were compared the risk of subsequent hematologic malignancy in IBD cohort.
Results: We included 3,547 enrollee with IBD during the period of 2000-2009. Male predominant (58.8%) was noted and age distribution were 42.6%, 31.4%, 26.0% at 18-44, 45-64, above 65 year-old, respectively. Of 3,547 IBD subjects, 57patients acquired hematologic malignancies during the follow-up time. When further sorting of specific malignancy, the adjusted HR were 8.04 for myeloid leukemia, 3.92 for lymphoblastic leukemia and 4.12 for non-Hodgkin's lymphoma. Patients with IBD who had received non-drug and only one class of drug were associated with increased risk of hematologic malignancy at 6.36-fold (95% CI: 3.66-11.05) and 4.08-fold (95% CI: 2.45- 6.79) than non-IBD patients. Among the using drugs, none of these classes of drug influence the contribution of subsequent hematologic malignancy.
Conclusions: In present study, we demonstrated the risk of hematologic malignancies related to the natural course of IBD, but not to the administrated drugs in Asian population.

ABSTRACT...............................................	I
中文摘要................................................	III
誌謝....................................................	V
TABLE OF CONTENTS......................................	VI 
LIST OF TABLES.........................................	VII
LIST OF FIGURES........................................	VIII
ABBREVIATION...........................................	IX
CHAPTER 1. INTRODUCTION............................... 	1
1.1. Different characters of IBD in epidemiology.......	2
1.2. Etiologies related to IBD........................ 	2
1.3. Present evidences of various cancer in IBD patients...............................................	3
1.4. The risk of hematologic neoplasm in IBD patients proven by previous literatures.........................	4
1.5. Treatment-related malignant neoplasm among IBD patients...............................................	5
CHAPTER 2. MATERIALS AND METHODS.......................	8
2.1. Database obtained from National Health Research Institute..............................................	8
2.2. Study sample and design.......................... 	9
2.3. Specific aims of the study....................... 	10
2.4. Covariates.......................................	10
2.5. Statistical analysis............................. 	12
CHAPTER 3. RESULTS.................................... 	13
3.1. Baseline demographic of IBD subjects and comparison group in our cohort................................... 	13
3.2. The increased risk of hematologic malignancy in IBD subjects.............................................. 	13
3.3. The risk of hematology neoplasm in IBD patients stratifying by age.....................................	13
3.4. The risk of hematology neoplasm in IBD patients after classifying subgroups of specific hematologic neoplasm.	14
3.5. The drugs effect on the risk of hematologic neoplasm.............................................. 	15
CHAPTER 4. DISCUSSION................................. 	17
4.1. The strength of our study........................ 	17
4.2. Compare the differences between our study and previous literature............................................ 	17
4.3. The matter of drugs for IBD and hematologic neoplasm formation............................................. 	18
4.4. The tentative mechanism of oncogenesis in IBD in vivo.................................................. 	19
4.5. The limitations of our study..................... 	20
CHAPTER 5 CONCLUSIONS................................. 	22
CHAPTER 6. REFERENCES.................................	23
 
Table 1. Demographic characteristics of the patients with IBD and the comparison group in Taiwan during the period 2000-2009.............................................	29
Table 2. Hazard ratios of cancer among the patient sample with stratification of gender.........................	30
Table 3. Crude and adjusted hazard ratios of hematologic neoplasm among the cohort of sampled patients stratified by sex and age group.....................................	31
Table 4. Hazard ratios of the specific sites of hematologic neoplasm in the patient sample........................ 	32
Table 5. Hazard ratios of the specific sites of hematologic neoplasm in the Crohn's disease and ulcerative colitis patients...............................................	34
Table 6. Hazard ratios of the specific sites of hematologic neoplasm in the Crohn's disease and ulcerative colitis patients by Catastrophic Illness Card..................	35
Table 7. The risk of hematologic malignancy in subjects who had ever received numbers of classification of drugs.. 	36
Table 8. Compare the risk of hematologic malignancy between users and non-users of five classes of IBD medication. 	37
Table 9. Risk of hematologic malignancy in IBD patients in various drugs combination............................. 	38
Figure 1. Study flow chart............................	39
                                    

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校內：2021-07-01公開
校外：2021-07-01公開

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