目的：胰臟癌是全球性的疾病，即使現在醫療技術進步，胰臟癌的預後仍然非常差；鑑於預防勝於治療，本研究期望透過臺灣全民健康保險資料庫及重大傷病資料庫的分析，探討與罹患胰臟癌有相關的疾病，藉以瞭解胰臟癌的可能成因。
方法：本研究係全人口資料庫為基礎的病例對照研究，研究納入2010年1月1日至2013年12月31日期間新診斷胰臟癌且領有重大傷病證明的病患作為病例組共3,726人，以胰臟癌的初診日為研究基準日，再依病例組的年齡、性別、居住地城鄉別、健保投保薪資級距等特性進行配對，選取3,726人作為對照組。以研究基準日往前追朔，探討在首次被診斷為胰臟癌的1至 9年以前之疾病史。首先使用單變數條件邏輯式廻歸篩選偽發現率( False discovery rate, FDR)達顯著相關之疾病，再將篩選出來的疾病以逐步篩選的方式進行多變項分析得到最顯著相關之疾病。最後，利用路徑分析探討篩選出的疾病與胰臟癌的關係路徑。
結果：經過多變數分析，與胰臟癌的發生率呈現正相關的疾病有9個，負相關則有2個，共11個疾病。多數的疾病在初次診斷為胰臟癌1以前或3年以前即有顯著相關，其中，7年以前就有顯著相關的疾病為消化性潰瘍、糖尿病、其他與腹部和骨盆相關之症狀。而在路經分析圖中，也可以發現糖尿病及胰臟炎對於胰臟癌有正向的直接影響，而失智症則有負向的直接影響。
結論：本病例對照研究發現的結果與前人研究一致，糖尿病、胰臟炎、消化性潰瘍及腹痛對於罹患胰臟癌有顯著正相關，而失智症則是有顯著負相關。其他篩選後的疾病像是腸胃道潰瘍、腹部相關症狀、黃疸、體重減輕、腸胃道出血等，皆與胰臟癌顯著相關。

Objective: Pancreatic cancer is prevalent globally. Despite advancements in medical technology, the prognosis remains dismal. Given that “a preventative approach is preferred to a curative approach.” this study attempted to understand the possible causes of pancreatic cancer through an analysis of Taiwan’s National Health Insurance Research Database (NHIRD) and Registry for Catastrophic Illness Patient Database (RCIPD).
Method: This case-control study based on a total population database. We included 3,726 patients with pancreatic cancer and diagnosis with a certificate of catastrophic Illness from January 1, 2010 to December 31, 2013. The primary diagnosis date of pancreatic cancer was set as the index date. According to the age, gender, residence of the case group, and insurance premium of the health insurance, the 3,726 non-pancreatic cancer patient was matched as the control group. We screened the disease by the first to ninth year before the first diagnosis of pancreatic cancer. The analysis used a univariate conditional logistic regression analysis to screen prior diseases associated with pancreatic cancer (False discovery rate< 0.05). These diseases were then analyzed by multivariate conditional logistic regression find the most significant associated disease with stepwise selection. Finally, path analysis was used to explore the relationship between the selected diseases and pancreatic cancer.
Results: In total, 11 prior diseases were associated with pancreatic cancer, of which nine were positive and two were negative associations. Most of the associated diseases only exhibited a relevant association with pancreatic cancer 1 or 3 years prior to the index date. Peptic ulcer, other symptoms involving the abdomen and pelvis, and diabetes mellitus were associated with pancreatic cancer 7 years prior to the date of first pancreatic cancer diagnosis. In the path diagram, the direct effect on pancreatic cancer is diabetes mellitus, pancreatitis, dementia. Diabetes mellitus and pancreatitis are positively correlated, dementia are negatively correlated.
Conclusion: After a comprehensive screening of the past diseases of pancreatic cancer, diabetes mellitus, pancreatitis, peptic ulcer, and abdominal pain have a significant positive correlation with pancreatic cancer, while dementia has a significant negative correlation. Other screened disease variables such as gastrointestinal ulcer, other symptoms involving abdomen and pelvis, jaundice, weight loss, gastrointestinal hemorrhage were all significantly associated with pancreatic cancer. In summary, the results were consistent with those of previous studies in the literature.

1 Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2017. CA: A Cancer Journal for Clinicians 67, 7-30, doi:10.3322/caac.21387 (2017).
2 Kamisawa, T., Wood, L. D., Itoi, T. & Takaori, K. Pancreatic cancer. The Lancet 388, 73-85, doi:https://doi.org/10.1016/S0140-6736(16)00141-0 (2016).
3 Rahib, L. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer research 74, 2913-2921, doi:10.1158/0008-5472.can-14-0155 (2014).
4 Ferlay, J., Partensky, C. & Bray, F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. Acta Oncologica 55, 1158-1160, doi:10.1080/0284186X.2016.1197419 (2016).
5 Goral, V. Pancreatic Cancer: Pathogenesis and Diagnosis. Asian Pacific journal of cancer prevention : APJCP 16, 5619-5624 (2015).
6 Higuera, O. et al. Management of pancreatic cancer in the elderly. World journal of gastroenterology 22, 764-775, doi:10.3748/wjg.v22.i2.764 (2016).
7 Ministry of Health and Welfare, T., R.O.C. 2017 Cause of Death Statistics. (2017).
8 Midha, S., Chawla, S. & Garg, P. K. Modifiable and non-modifiable risk factors for pancreatic cancer: A review. Cancer Letters 381, 269-277, doi:https://doi.org/10.1016/j.canlet.2016.07.022 (2016).
9 Vincent, A., Herman, J., Schulick, R., Hruban, R. H. & Goggins, M. Pancreatic cancer. Lancet (London, England) 378, 607-620, doi:10.1016/S0140-6736(10)62307-0 (2011).
10 Hussain, S. P. Pancreatic Cancer: Current Progress and Future Challenges. International journal of biological sciences 12, 270-272, doi:10.7150/ijbs.14950 (2016).
11 Torphy, R. J. & Schulick, R. D. Screening of Patients at Risk for Familial Pancreatic Cancer: What Is Bene fi cial? The Surgical clinics of North America 98, 25-35, doi:10.1016/j.suc.2017.09.003 (2018).
12 Bosetti, C. et al. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 23, 1880-1888, doi:10.1093/annonc/mdr541 (2012).
13 Chuang, S.-C. et al. Exposure to environmental tobacco smoke in childhood and incidence of cancer in adulthood in never smokers in the European prospective investigation into cancer and nutrition. Cancer Causes & Control 22, 487-494, doi:10.1007/s10552-010-9723-2 (2011).
14 Ben, Q. et al. The relationship between new-onset diabetes mellitus and pancreatic cancer risk: a case-control study. Eur J Cancer 47, 248-254, doi:10.1016/j.ejca.2010.07.010 (2011).
15 Hao, L. et al. Incidence of and risk factors for pancreatic cancer in chronic pancreatitis: A cohort of 1656 patients. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 49, 1249-1256, doi:10.1016/j.dld.2017.07.001 (2017).
16 Preziosi, G., Oben, J. A. & Fusai, G. Obesity and pancreatic cancer. Surgical Oncology 23, 61-71, doi:https://doi.org/10.1016/j.suronc.2014.02.003 (2014).
17 Xu, M., Jung, X., Hines, O. J., Eibl, G. & Chen, Y. Obesity and Pancreatic Cancer: Overview of Epidemiology and Potential Prevention by Weight Loss. Pancreas 47, 158-162, doi:10.1097/mpa.0000000000000974 (2018).
18 Chu, C. K. et al. Preoperative diabetes mellitus and long-term survival after resection of pancreatic adenocarcinoma. Annals of surgical oncology 17, 502-513, doi:10.1245/s10434-009-0789-6 (2010).
19 Roeyen, G. et al. Diabetes mellitus and pre-diabetes are frequently undiagnosed and underreported in patients referred for pancreatic surgery. A prospective observational study. Pancreatology 16, 671-676, doi:https://doi.org/10.1016/j.pan.2016.04.032 (2016).
20 Munigala, S., Singh, A., Gelrud, A. & Agarwal, B. Predictors for Pancreatic Cancer Diagnosis Following New-Onset Diabetes Mellitus. Clinical and translational gastroenterology 6, e118, doi:10.1038/ctg.2015.44 (2015).
21 Rijkers, A. P. et al. Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis. Pancreas 46, 1018-1022, doi:10.1097/mpa.0000000000000879 (2017).
22 Sun, J. Y., Sun, D. J., Li, X. J., Jiao, K. & Zhai, Z. W. Laparoscopic treatment experience of severe acute pancreatitis complicated by peptic ulcer perforation. European review for medical and pharmacological sciences 20, 285-290 (2016).
23 National Health Insurance Administration, M. o. H. a. W., Taiwan, R.O.C. National Health Insurance Annual Report 2017-2018. 14-27 (2017).
24 National Health Insurance Research Database, T. Data Subsets, <http://nhird.nhri.org.tw/en/index.htm> (2015).
25 National Health Insurance Administration, M. o. H. a. W., Taiwan, R.O.C. 201811National Health Insurance Serious Disabling Disease Certificate Valid Licence Statistics. (2018).
26 Bao, Y. et al. History of peptic ulcer disease and pancreatic cancer risk in men. Gastroenterology 138, 541-549, doi:10.1053/j.gastro.2009.09.059 (2010).
27 Lee, J. E., Kim, D. & Lee, J. H. Association between Alzheimer's Disease and Cancer Risk in South Korea: an 11-year Nationwide Population-Based Study. Dementia and neurocognitive disorders 17, 137-147, doi:10.12779/dnd.2018.17.4.137 (2018).
28 Peynircioglu, B., Karaosmanoglu, A. D., Idilman, I. S., Akata, D. & Simsek, H. Intrapancreatic pseudoaneurysm causing massive gastrointestinal hemorrhage and chronic pancreatitis. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 26, 270-273, doi:10.5152/tjg.2015.6548 (2015).
29 Woods, M. S., Traverso, L. W., Kozarek, R., Brandabur, J. & Hauptmann, E. Successful treatment of bleeding pseudoaneurysms of chronic pancreatitis. Pancreas 10, 22-30 (1995).
30 Zhu, L. et al. Multiple solid pancreatic lesions: Prevalence and features of non-malignancies on dynamic enhanced CT. European Journal of Radiology 105, 8-14, doi:https://doi.org/10.1016/j.ejrad.2018.05.016 (2018).
31 Ravindran, R. Chronic pancreatitis. Surgery (Oxford) 37, 336-342, doi:https://doi.org/10.1016/j.mpsur.2019.03.002 (2019).