膽石症患者的膽管癌風險

Risk of Cholangiocarcinoma in Cholelithiasis Patients

汪奇志(Chi-Chih Wang)

指導教授 ： 林俊哲

中山醫學大學/醫學院/醫學研究所/博士(2019年)

https://doi.org/10.6834/CSMU201900087

摘要

研究目的
膽管癌是一種高度致命的疾病，在過去二十年中一直沒有得到應有的重視。 膽管癌中存在許多致病的危險因子，其中膽石症是盛行率高且重要的膽管癌的危險因子，同時，先前膽管介入性治療的影響，如內視鏡下括約肌切開術（ES），內視鏡乳頭球囊擴張術（EPBD）和膽囊切除術，在以前的文獻中對膽管癌的影響是不一致的。 我們使用國家健康保險研究數據庫（NHIRD）進行了這項研究，以闡明膽石症的病人接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術，膽囊切除術或無進行侵入性治療的後續膽管癌的風險。另外，在進一步的研究中，我們把患者縮小為膽管結石住院的患者，觀察在接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術後，六個月內有無接受膽囊切除術，對於後續產生膽囊癌症的影響，以及這個影響與反覆性的膽道發炎反應之間的相關性。

研究方法
根據國家健康保險研究數據庫2004-2011的數據，我們選擇了7938例膽石症病例和23,814例對照組病例（性別和年齡按1：3比例匹配）。 我們比較了膽石症組和對照組膽管癌和膽管癌的危險因子在兩組間的分佈狀況。在接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術的患者，接受膽囊切除術的患者，僅保守性治療的膽石症患者和來自正常人群的組中計算全膽管癌和後續膽管癌的發生率。接下來進一步縮小患者至因膽管結石或膽管炎住院的患者，以接受保守性療法的病人當做對照組，觀察接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術的患者以及在內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術後追加膽囊切除術的患者，後續膽管癌症的比率以及是否與反覆性的膽道發炎事件相關。

研究結果
本研究於健保資料庫100萬人中找出7938例膽石症病例和23,814例對照組病例（性別和年齡按1：3比例匹配），結果發現接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術患者537例，膽囊切除術1743例，膽石症患者僅接受保守性治療5658例。後續產生膽管癌的患者中有11例（2.05％）發生在接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術組，37例（0.65％）發生在保守治療組和7例（0.40％）發生在膽囊切除組，後續膽管癌的勝算比以保守治療組為基準，接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術組為3.13，在膽囊切除術的組別中為0.61。在進一步的針對膽管結石住院的病人統計後，以保守治療組當做基準，可以發現內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術組的18個月後產生膽管癌的勝算比是3.17倍，若是內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術合併膽囊切除術的組別的勝算比是1.35，同時我們發現追蹤18個月以上得到膽管癌的病人與沒有得到膽管癌的病人相比，有得到膽管癌的患者再發性膽管事件的發生比率是527.79/ 1000人年而沒有得到膽管癌的患者的再發性膽管事件的發生比率明顯較低，為286.69/1000人年，且達到明顯的統計學上的差異。

結論
膽石症患者接受膽囊切除術可以降低後續膽管癌的發生率，而接受內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術治療的膽石症患者在我們的報告中存在後續膽管癌的巨大風險。另外，在於膽管結石及膽管炎住院的病人當中，在接受過內視鏡下括約肌切開術/內視鏡乳頭球囊擴張術的病人當中，膽囊切除術可以藉由下降再發性膽道發炎事件的發生，進一步減少長期的膽管癌發生率。

關鍵字

膽管癌 ； 內視鏡下括約肌切開術 ； 內視鏡乳頭球囊擴張術 ； 膽囊切除術

並列摘要

Background and Aims: Cholangiocarcinoma had been underestimated in the past two decades. Many risk factors are well documented in cholangiocarcinoma, but the impacts of advanced biliary interventions, like endoscopic sphincterotomy (ES), endoscopic papillary balloon dilatation (EPBD), and cholecystectomy, are inconsistent in the previous literature. To clarify the risks of subsequent cholangiocarcinoma in cholelithiasis patients, we use the National Health Insurance Research Database (NHIRD) to setup this study. Furthermore, we focus on hospitalized patients due to choledocholithiasis and observe whether cholecystectomy after endoscopic sphincterotomy/endoscopic papillary balloon dilatation can reduce subsequent cholangiocarcinoma rate. We also check the relationships between recurrent biliary events and the subsequent cholangiocarcinoma rate.
Method: From data of NHIRD 2004-2011 in Taiwan, we selected 7938 cholelithiasis cases as well as 23814 control group cases (matched by sex and age in a 1:3 ratio). We compared the previous risk factors of cholangiocarcinoma and cholangiocarcinoma rate in the cholelithiasis group and control group. The incidences of total and subsequent cholangiocarcinoma were calculated in ES/EPBD patients, cholecystectomy patients, cholelithiasis patients without intervention, and groups from the normal population. In the next step, hospitalized patients because of bile duct stones or cholangitis were included. Patients receiving conservative treatment were used as a control group comparing to patients undergoing endoscopic sphincterotomy/endoscopic papillary balloon dilatation with or without cholecystectomy. We analyzed the rate of subsequent cholangiocarcinoma and whether it is associated with the frequency of recurrent biliary events.
Result: In total, 537 cases underwent ES/EPBD, 1743 cases underwent cholecystectomy, and 5658 cholelithiasis cases had no intervention. Eleven (2.05%), 37 (0.65%), and 7 (0.40%) subsequent cholangiocarcinoma cases were diagnosed in the ES/EPBD, no intervention, and cholecystectomy groups, respectively, and the odds ratio for subsequent cholangiocarcinoma was 3.13 in the ES/EPBD group and 0.61 in the cholecystectomy group when compared with the no intervention group.
After further statistics on patients hospitalized for bile duct stones, using the conservative treatment group as a reference, the odds ratio, for subsequent cholangiocarcinoma at least 18 months later, was 3.17 in ES/EPBD group and 1.35 in ES/EPBD and further cholecystectomy group. Compared with choledocholithiasis patients who had subsequent cholangiocarcinoma, the incidence of recurrent bile duct events was significantly lower as 286.69/1000 person-years v.s. 527.79/1000 person-years, in choledocholithiasis patients without subsequent cholangiocarcinoma.
Conclusion: In conclusion, cholelithiasis patients who undergo cholecystectomy can reduce the incidence of subsequent cholangiocarcinoma, while cholelithiasis patients who undergo ES/EPBD are at a higher risk of subsequent cholangiocarcinoma according to our findings.
In addition, among patients hospitalized for bile duct stones and cholangitis, patients who underwent ES/EPBD, cholecystectomy can reduce subsequent cholangiocarcinoma rates through reducing recurrent biliary events.

並列關鍵字

cholangiocarcinoma ； endoscopic sphincterotomy ； endoscopic papillary balloon dilatation ； cholecystectomy

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