探討肝內膽管癌接受肝切除手術病患之臨床療效及醫療資源耗用之研究

A Cohort Longitudinal Study of Clinical Outcomes and Resource Utilization for Patient with Liver Resection of Intrahepatic Cholangiocarcinoma

江芝儀(Chih-Yi Chiang)

指導教授 ： 李金德

高雄醫學大學/健康科學院/醫務管理暨醫療資訊學系碩士在職專班/碩士(2016年)

摘要

研究目的:
惡性腫瘤為國人死因之首，肝及肝內膽管癌為癌症死因第二位，在美國癌症死因第五位。許多研究指出由於肝內膽管癌全球發病率及死亡率皆有上升的趨勢且預後不佳，治療方式如化學治療及其他輔助治療效果皆有限，唯一可延長生命方法即為外科手術治療或肝臟移植，但往往發現時已為晚期，約只有30~40%可接受手術治療。目前台灣並無肝內膽管癌接受肝切除手術之臨床療效及醫療資源耗用之相關探討，本研究主要探討肝內膽管癌接受肝手術切除病患之發生率及趨勢分析，並探討肝內膽管癌接受肝切除手術病患之住院期間醫療資源耗用及其相關影響因素，在進一步探討肝內膽管癌肝切除手術病患醫療療效及其相關影響因素。

研究方法:
本研究為回溯性次級資料的縱貫研究分析(Retrospective longitudinal study)。從「全民健康保險研究資料庫」中，選取國際疾病分類第九版診斷肝內膽管癌合併肝切除手術代碼為(ICD-9-CM 1551、5022、503)，研究期間為1999年至2012年，研究對象為肝內膽管癌接受肝切除手術病患。研究資料以SPSS for Windows 20.0 統計套裝軟體做為分析工具。

研究結果:
14年總樣本數為1295人中分析發現，肝內膽管癌接受手術病患的發生率由每十萬人口從0.35增加至0.77，有逐年上升趨勢，其中以女性居多，平均年齡為63.07歲，接受肝部分切除手術724人(57.3%)居多。醫療資源耗用的分析中，研究發現影響住院天數以及住院費用因素有年齡、B型肝炎、合併症嚴重度、手術治療方式、醫師服務量及年代。存活分析方面肝內膽管癌不論是接受肝部分切除手術或是肝葉切除手術對整體存活期在統計上無顯著影響(P=0.496)，在無病存活期部分也呈現無顯著差異(P=0.984)。死亡風險評估方面肝內膽管癌手術病患年齡75歲死亡風險是54歲的1.49倍;合併症嚴重度指標(CCI) 3-5分死亡風險是CCI 2分的1.27倍、CCI 6分死亡風險是CCI 2分的2.79倍。年代T2(2003-2007年)死亡風險是年代T1(1999-2002年)的 0.76倍(P<0.003)，年代T3(2008-2012年)死亡風險是年代T1的 0.27倍(P<0.001)。但在手術治療方式發現肝葉切除手術較肝切除手術死亡風險雖為1.06倍，但在統計學上無顯著差異(P=0.503)。

討論與建議:
研究發現肝內膽管癌手術病患發生率分布趨勢有逐年上升之情形，住院天數及費用隨著年代有下降之趨勢，高醫院服務量及高醫師服務量對住院天數、費用及死亡率皆有下降之影響，增加其醫療品質。肝內膽管癌病患接受肝部分及肝葉切除手術病患中，發現兩種術式並無影響其存活，反倒是在年齡、合併症嚴重指標、醫院及醫師服務量，是肝內膽管癌手術病患之死亡率及存活率顯著相關影響因子。此研究結果在兼顧醫療品質及經營效益下能提供醫師及臨床病患治療模式、衛生主管機關及醫院管理者在規劃醫療資源預算和未來推動衛生政策參考依據。

關鍵字

肝內膽管癌 ； 肝切除手術 ； 存活率 ； 趨勢分析 ； 醫療資源耗用

並列摘要

Background and Purposes:
Malignant carcinoma is the leading cause of national mortality, where hepatocellular carcinoma and intrahepatic cholangiocarcinoma is the second most common form of cancer deaths in this country. Many studies have reported an increase in global morbidity and mortality incidences of intrahepatic cholangiocarcinoma with poor prognosis. Patients are presented to the clinic with advanced stages of intrahepatic cholangiocarcinoma therefore only about 30% to 40% meet the criteria for surgical intervention.This study aims to investigate the incidences of liver resection for intrahepatic cholangiocarcinoma and conduct a trend analysis into medical resource utilization and management for hospital stays, as well as treatment efficacy of intrahepatic cholangiocarcinoma patients who underwent liver resection.

Methodology:
This study is a retrospective longitudinal study of secondary data sources (Retrospective longitudinal study). Cases were selected from the "National Health Insurance Research Database, Diseases diagnosis of intrahepatic cholangiocarcinoma and liver resection codes (ICD-9-CM 1551, 5022, 503). The study cases were selected between 1999-2012, inclusion criterion is intrahepatic cholangiocarcinoma patients who underwent liver resection( partial hepatectomy or lobectomy). Statistical analysis was conducted in the “SPSS for Windows 20.0” statistical software package.

Results:
The incident rate, per 100 000 persons, of intrahepatic cholangiocarcinoma over a 14 year period had increased from 0.35 to 0.77, with an annual increase trend observed. Majority of cases were female with an average age of 63.07 years, and most common surgical intervention is partial hepatectomy n=724 (57.3%). Several factors affected the length of hospital stay, and costs, including age, hepatitis B, the severity of complications, type of surgical intervention, physician attendance and era of admission. In intrahepatic cholangiocarcinoma survival rate, there was no significant correlation between partial hepatectomy or lobectomy(P = 0.496), nor is there between healthy and diseased patients (P = 0.984). Mortality risk assessment in patients with intrahepatic cholangiocarcinoma surgery aged 75 years, when compared to 54 years, showed an age-related risk of 1.49-fold; the severity of Charlson comorbidity index (CCI) 3-5 had a risk of mortality 1.27 times that of CCI-2, CCI 6 had a risk of mortality 2.79 times that of CCI-2. Era T2's risk of mortality is 0.76 times that of Era T1 (P <0.003); the risk of mortality for Era T3 is 0.27 times that of Era T1 (P <0.001). In surgical treatment, however,lobectomy had an increased risk of mortality of 1.06 times, but there was no significant difference overall (P = 0.503).

Conclusions:
The study observed an annual increase in the incidences of intrahepatic cholangiocarcinoma cases requiring surgical intervention, accompanied by a decrease in the duration of hospital stays and costs over the study’s designated eras. Hospital volume and surgeon volume also contributed to a decrease in hospital stays, costs and mortality. Surgical treatments partial hepatectomy or lobectomy for intrahepatic cholangiocarcinoma patients had no effect on the survival rate; instead age, CCI, and high hospital volume and surgeon volume had more significant impact on a positive patient outcome.

並列關鍵字

Intrahepatic cholangiocarcinoma ； liver resection ； survival rate ； trend analysis ； medical resource utilization

參考文獻

1.American Cancer Society (2015) Cancer Facts & Figures 2015.Atlanta, Ga:American Cancer Society

2.Amini, N., Ejaz, A., Spolverato, G., Kim, Y., Herman, J. M., & Pawlik, T. M. (2014). Temporal trends in liver‐directed therapy of patients with intrahepatic cholangiocarcinoma in the United States: A population‐based analysis. Journal of surgical oncology, 110(2), 163-170.

3.Anderson, J. E., Hemming, A. W., Chang, D. C., Talamini, M. A., & Mekeel, K. L. (2012). Surgical management trends for cholangiocarcinoma in the USA 1998–2009. Journal of Gastrointestinal Surgery, 16(12), 2225-2232.

4.Bergeat, D., Sulpice, L., Rayar, M., Edeline, J., Merdignac, A., Meunier, B., . . . Boudjema, K. (2015). Extended liver resections for intrahepatic cholangiocarcinoma: Friend or foe? Surgery, 157(4), 656-665.

5.Bertuccio, P., Bosetti, C., Levi, F., Decarli, A., Negri, E., & La Vecchia, C. (2013). A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol, 24(6), 1667-1674. doi:10.1093/annonc/mds652